Essays, poems and Stories of an African-American

Wednesday, 25 March 2015

Plan for being and staying "undetectable" or "negative." There are discipline issues! Enjoy article!

Ask a Pharmacist: The Journey to “Undetectable”

When a person living with HIV, together with his or her clinician, decides it is the right time to start antiretroviral therapy (ART), one major goal is usually to “get to undetectable“—that is, to suppress viral replication so that very low levels of virus remain.
And today, that goal is more attainable than ever. “With the currently available potent HIV regimens, I don’t see why we can’t achieve close to 100% of patients reaching undetectable viral loads,” says Chris Nguyen, an HIV pharmacist with Walgreens in San Francisco.
Read on to understand how undetectable viral load is reached, and for tried-and-true strategies and tips for keeping the virus in check.

Measuring the Descent

The journey to undetectable is similar to climbing down a steep mountainside to safer ground. Viral load is like a marker of your descent down the mountain, and antiretroviral therapy (ART) can be seen as a rope you use to climb down safely.
Within six weeks of starting ART, your clinician is looking for a sharp drop in your viral load, usually a 1-log drop. (Click here for a handy cheat sheet on “log” changes.) For example, on the logarithmic scale, a viral load of 100,000 copies/mL is equal to 5 log copies/mL. After six weeks, your clinician might check to see whether the viral load has decreased to approximately 4 log copies/mL (10,000 copies/mL), which represents a 1-log reduction. After 24 weeks, highly effective ART should result in an undetectable viral load.
Some people mistakenly think that being “undetectable” means that there is no HIV virus left in the body. This is not the case. “Undetectable” means that there is such a small quantity of virus circulating in the blood that none was seen in a particular blood sample.
One of two assays, either reverse transcriptase polymerase chain reaction (RT-PCR) or branched DNA (bDNA), is typically used to measure the amount of HIV-RNA (HIV’s genetic material), in a small sample of blood. Each assay gives a good estimate of the burden of virus in the body, but lab machinery is never perfect, and both the RT-PCR and bDNA have upper and lower limits to how well they represent virus levels. In addition, some cells contain dormant HIV that is not currently replicating but has the potential to do so. These cells make up the “latent HIV reservoir,” and RT-PCR and bDNA assays cannot measure the amount of virus they contain.
For these reasons, when you have an undetectable viral load, your count is not listed as “zero”; it may instead be listed as <75 copies/mL (for a bDNA test) or <20 copies/mL (for the most sensitive RT-PCR). There is some variation between the standard tests used to monitor viral load; clinicians typically aim for the ART regimen to suppress the virus to below 50 copies/mL.
Why do clinicians strive for undetectable? “Keeping an undetectable viral load allows your immune system to begin its recovery and means the virus will not develop resistance to your meds,” says Dr. Ruth Greenblatt, a physician at San Francisco General Hospital with more than 20 years of experience caring for people living with HIV and AIDS.

What It Takes

Like climbing down a mountain, getting to undetectable takes some work, but it is possible with the right equipment. Suppressing HIV to undetectable levels depends on finding the right regimen—and sticking to it—to stop the virus from hijacking more of the body’s cells and making new copies of itself.
Adhering to an ART regimen is one of the foundations of HIV treatment, and it can take some getting used to. (See below for some strategies to boost adherence.) But today, as Dr. Nguyen points out, “many of the regimens are very well tolerated, which helps.” And the rewards are huge: “I remember one of my newly diagnosed patients coming in a month after starting his regimen, raving about how his viral load has drastically dropped in such a short amount of time, and how happy his provider was,” Dr. Nguyen recalls. “It brought a big grin to my face seeing how excited he was.”
Good adherence involves taking the right pills at the right time on a regular basis, to keep drug levels high enough to continually suppress HIV replication. When you interrupt your ART or miss doses, the levels of those HIV-fighting drugs decline—sometimes imperceptibly, sometimes quit a bit. When drug levels decline too far to keep the virus in check, HIV can resume replicating, and viral load rises.

The Adherence–Resistance–Viral Load Connection

Closely connected to low adherence is the possibility of drug resistance. To keep HIV in check, an ART regimen must include drugs from multiple drug classes that block replication at different stages in the viral lifecycle. When missed doses cause drug levels of one or more medications to fall and the virus replicates, the new copies may contain genetic mutations against those drugs, rendering them less effective or even ineffective and limiting future options for treatment.
Scientists and clinicians know that low adherence can lead to HIV drug resistance, but they are still trying to better understand the specifics. For example, many people living with HIV have long been advised to take at least 95% of their medicines each month. It is certainly true that adhering your regimen at least 95% of the time can help avoid resistance and keep your viral load undetectable. However, researchers are currently exploring whether lower levels of ART adherence may be possible without sacrificing viral suppression.
Dr. David Bangsberg’s studies in the San Francisco–based REACH cohort found that a group of people on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens still had an undetectable viral load even though they were skipping 25%–50% of their doses. Other researchers are also beginning to recognize that different patterns of adherence (such as skipping on the weekends versus skipping more sporadically) may have different impacts on resistance and viral load. And another study found that participants who had been undetectable for twelve months prior to skipping doses had a 47% lower risk of virologic failure (that is, failure of the drugs to keep the virus suppressed) compared with those who had been undetectable for only one month before reducing their adherence.
That said, the jury is still out on the long-term effects of “drug holidays” and low adherence. Conducting these types of studies helps scientists, clinicians, and people living with HIV learn about patterns of adherence that may be harmful, and what effect the occasional missed dose might have. We have not yet learned enough to translate these studies into practice, so taking ART consistently is still the best way to keep the virus undetectable.
If you find yourself skipping doses (or wanting to skip them), have an open conversation with your clinician about it. She or he may be able to guide your adherence strategies, discuss simpler regimens, and/or address any side effects or other issues that you may be finding a challenge.

Preparing for Your Journey

As you prepare to get your HIV viral load undetectable, there are several things you can do to ensure a successful journey. First, consider your clinician: How’s your “patient-provider relationship”? Do you feel your clinician listens to your questions? Are you comfortable having honest conversations about your ART, possible side effects, and any concerns you have about adhering to your regimen? Good communication with your medical team is essential to getting the care you need as you work toward an undetectable viral load.
Click here for resources to help you build a strong partnership with your doc—or make a fresh start with a new clinician.
Next, you’ll want to set yourself up to create good adherence habits. Although the studies described above suggest that lower levels of ART adherence may not be as harmful as was once thought, the best way to get (and keep!) your HIV undetectable is to aim for consistent adherence to your regimen.

Make an Adherence Plan

Think about your daily routines and consider where taking your medicines will fit. For example, you probably rarely for­get to brush your teeth in the morning, so you might plan to take your medi­cines right before brushing your teeth.
Also think about what motivates you in other areas of your life. Do you reward yourself after cleaning the kitchen or hitting the gym? Can you motivate yourself with the same (healthy!) rewards after a week of solid adherence to your ART?
Finally, it may be helpful to examine your mindset about taking HIV medications. The pills or injections may at first seem like an unwelcome reminder of your virus, but those drugs also show that you are working to beat that virus, manage your health, and take care of yourself.

Ready Your Adherence Devices

Part of your adherence plan may include using medication reminder devices such as cell phone alarms or daily text messages. Personalizing the alarm or text with a motivating message may help.
ART medication packaging can also make a difference. Some people prefer to keep their med­icines in pillboxes marked with the days of the week so they can keep track of the doses they have already taken. Also, some HIV-specialized pharma­cies can package ART in pillboxes or in special daily “bubble” packaging.
Try to keep a supply of ART handy and refill your medicines 5–7 days ahead of time so that you don’t run out and miss doses. If getting to the pharmacy to pick up your medications is problematic, you may want to talk to the pharma­cist about getting medications deliv­ered or mail-ordered. You may also wish to set up automatic refills and reminder calls when your prescrip­tions are ready.

Assemble Your Support Team

Your adherence plan can also in­clude figuring out who your support network is and assembling a team of “medication cheerleaders.” These can be friends, family members, or other people living with HIV—anyone who can provide encouragement as you start new medications and/or deal with challenges to adherence.
You might ask this team to check on you in person, by phone or text, or online. If you are tak­ing a drug that may cause depression or other psychiatric side effects, you might consider asking your support team to watch out for these symptoms and be prepared to help you seek assistance. Sometimes just knowing that people are watching out for you can be comforting and motivating.
Lastly, don’t forget to ask for help from your health care team: your doctors, nurses, pharmacists, social workers, case managers, and others who are rooting for you to succeed in your journey to undetectable.
Jennifer Cocohoba, PharmD, is an associate clinical professor in the School of Pharmacy at the University of California, San Francisco (UCSF). Since 2004, she has worked as the clinical pharmacist for the UCSF Women’s HIV Program, where she provides adherence support and medication information to patients and providers.

Selected Sources

Bangsberg, D. Less than 95% adherence to nonnucleoside reverse-transcriptase inhibitor therapy can lead to viral suppression. Clinical Infectious Diseases 43(7):939–41. October 1, 2006.
Easterbrook, P. and others. The natural history and clinical significance of intermittent viraemia in patients with initial viral suppression to <400 copies/ml. AIDS 16(11):1521–27. July 26, 2002.
Geretti, A. and others. Determinants of virological failure after successful viral load suppression in first-line highly active antiretroviral therapy. Antiviral Therapy 13(7):927–36. 2008.
Palmer, S. Advances in detection and monitoring of plasma viremia in HIV-infected individuals receiving antiretroviral therapy. Current Opinion in HIV and AIDS 8(2):87–92. March 2013.
Parienti, J. and others. Not all missed doses are the same: sustained NNRTI treatment interruptions predict HIV rebound at low-to-moderate adherence levels. PLoS One 3(7):e2783. July 30, 2008.
Rosenblum, M. and others. The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy. PLoS One 4(9):e7196. September 29, 2009.

The beer belly issues among people on ART. Enjoy this article!

Abdominal Body Fat Gains on ART and Viral Load: It Matters Where You Start

BETA reported from last week’s 2015 Conference on Retroviruses and Opportunistic Infections in Seattle.
New research presented at CROI 2015 last week gave new insight about a puzzling aspect of antiretroviral therapy (ART): lipodystrophy, or changes in body fat distribution. New findings show that people with higher viral loads when starting ART for the first time are more likely to undergo substantial body composition changes, such as an increased amount of fat in the abdominal area (called “central adiposity”), than those who start treatment with a lower viral load (abstract 140). This finding presents another reason why it’s important to start HIV treatment early.
Though it’s unclear why people on ART get lipodystrophy, protease inhibitors have, in the past, been suspected of causing body fat changes. Grace McComsey, MD, from Case Western Reserve University, presented new evidence that HIV, viral load and inflammation may also play a role in body composition changes above and beyond that which may be caused by any specific drug regimen.
In her study, treatment-naïve people with HIV who had viral loads in the highest range (over 100,000 copies/mL) before starting treatment had greater gains in abdominal fat and peripheral fat (e.g., fat on arms and legs) than people starting treatment with lower viral loads. People with higher IL-6 (a marker of immune activation) before starting treatment also had greater gains in peripheral fat.
A total of 328 people with no prior ART experience took part in the randomized controlled study, and were followed for a total of 96 weeks. Most (90%) of the participants were men, and the median age of study participants was 36. They were assigned to take tenofovir/emtricitabine (Truvada) plus one of the following combinations: 1) the protease inhibitor atazanavir and ritonavir (Reyataz and Norvir); 2) the protease inhibitor darunavir and ritonavir (Prezista and Norvir); or 3) the integrase inhibitor raltegravir (Isentress).
The researchers hypothesized that different medications would have different effects on fat gain. That’s not what they saw, however.
Using a body composition X-ray scan called DEXA, the research team found that men across all three study groups gained limb fat over the course of the study—with no differences based on the medication participants in each group were taking. Average increases per group ranged between 11% and 20%. Men also increased their abdominal fat by an average of 16% to 29% during the study—again, with no significant differences between medication groups.
Body mass increased during the study, with gains in all three study groups ranging from 3% to 3.5%.
In a question and answer session after her talk, McComsey showed concern about their findings, saying, “A 30% gain in fat after two years—that’s really bad. That’s a relatively short duration of treatment.”
Because there were no differences that seemed to be associated with the type of ART regimen, the researchers looked back to see if any of the factors they measured at baseline might be related to their findings. That’s when they realized, according to to McComsey, that viral loads prior to starting ART had an effect on later fat gain.
“Regardless of the treatment regimen, people who started at the high viral load strata gained double or triple the amount of fat than people who started at the lower viral load strata,” explained McComsey. Their findings provide another reason why it’s important to start HIV medications soon after diagnosis, and not wait until viral loads are elevated or CD4 counts are low.
The fat gains seen in the study may not necessarily be a negative consequence for people with high viral loads when they begin ART. McComsey said that the people in their study with higher viral loads prior to initiating ART, “may be sicker, in a way,” than people with lower viral loads, and that a greater gain in fat  seen during ART may mark a “return to health.”

Multiple sex partners with or without protection against HIV? Read this exciting article

Promiscuous Gay Nerd: Choosing to Love Poz Guys

I met James1 on Grindr. Well, not exactly – he was a friend of a friend, who also happened to be a fan of my writing. We had connected years ago and intended to meet up, but we never found the time. So when James pinged me on Grindr, my interest was piqued. He was gorgeous, successful, and hung like a fucking horse. I thought to myself, “okay, what’s the catch?” We made plans to spend a weekend in his hometown, a two hour drive from me.
But before I got in my car and made the schlep over to see him, he texted me to say that he had something to tell me. Something I should know before we met. At this point, most gay men I know would be preparing to run for the hills. Having a Grindr trick tell you before you ever meet that there’s something you ought to know, without just spitting it out, is usually a code red situation. But I wasn’t most gay men. Quite the contrary: Rather than feeling anxious or ominously worried, I put my hands together like a skinny girl at McDonald’s and prayed, “Please let him say that he’s positive.”
To say that this is a new perspective for me is an understatement. Nearly two years ago, just a few weeks after I started taking Truvada daily for PrEP, I penned an article on “Learning to Fuck With Poz Guys.” In that piece, I talked openly about the challenges I experienced incorporating HIV-positive guys into my (mostly condomless) sex life. The writing on the wall was pretty clear then that sexual transmission is nearly impossible with guys who are on treatment, have undetectable viral loads, and do not have an STI co-infection. Despite that growing scientific consensus, I still struggled with my own irrational fears and deeply-ingrained stigmatizing views of HIV-positive men. Like most gay men, I had been trained to avoid HIV-positive guys at all cost. Sure, you could use condoms. But why risk it?
We know even more today than we did in 2012. The preliminary results from the PARTNER study released in March this year firmly planted the jaws of many in the field squarely on the floor. If you’re not familiar with the ongoing clinical trial tracking serodiscordant couples that don’t use condoms consistently, let me briefly rehash its findings thus far.  In two years, not one person with an undetectable viral load –gay or straight – had transmitted HIV to their primary partner, during an estimated 16,400 occasions of sex among gay men and 28,000 among straight couples.
The kicker for HIV-negative folks like me on PrEP: none of the HIV-negative partners in the PARTNER trial are on PrEP (or PEP, for that matter).
But all this science aside, why in the world would I pray for my new beau to be HIV-positive? Knowing that there’s no risk of infection is one thing. But to actually seek out and desire HIV-positive partners is quite another.
The answer, I think, lies in the spectacular failure of my last relationship.
Like so many gay couples, Tim and I fought tirelessly over monogamy. We were both sluts who clearly loved to spread our seed. I didn’t mind the idea of him having sex with other guys, but he was controlling and jealous. He ominously threatened one day that if I ever cheated on him, he would beat the shit out of me. I nervously laughed it off. He couldn’t be serious? Right?
When we finally did open the relationship, he insisted on all sorts of restrictions. It turns out those restrictions were only for me. No sex in our house, he said. I’d come home from work and find evidence to the contrary. I didn’t really care. But the real stickler was his insistence that we use condoms whenever we fucked outside the relationship. As the bottom in the relationship, my getting fucked condomless would threaten both his dominance over me and his HIV-negative status.
So when I found out he bred a friend of a friend in the woods outside a party while I was inside with friends, I was done. A few weeks later, when he went out to the bar with friends, I enacted my own form of resistance: I went out and got my ass creamed. It felt exhilarating – liberating, even.
When I came home, he was drunk and furious. Somehow, he seemed to know what I had done. I denied it. But as I walked up the steps to our apartment, he took his first swing – the beginning of a long night that ended with his arrest.
Throughout the entire relationship, HIV provided the rationale for Tim’s controlling jealousy in our open relationship. I’m under no illusion that this explanation is entirely legitimate; clearly, Tim had his own demons and insecurities that he desperately needed to deal with. Nonetheless, it was always lurking in the shadows of our relationship, providing a kind of scientific legitimacy to his control.
Tim’s behavior is an extreme example of what is a pretty common phenomenon for gay men I know. The fear of HIV leads gay men to all sorts of irrationalities. This is especially true for HIV-negative gay men, whose knowledge of the disease is largely fed by stigma and misinformation. When I came out to my parents at the age of 14, my parent’s first response was that I would probably die of AIDS. The LGBT youth group I attended regularly for the next two years didn’t teach me gay history; it taught me how to use a condom. Irregularities in the blood tests I needed to start Accutane in high school compelled my doctor to warn me that I might be HIV-positive. If a condom broke with a partner, I would get tested every month for the next six months – each time reading into some minute detail (the counselor’s tone of voice; his delay in returning to the testing room; an ominous voicemail)convinced that I was positive.
For most of my life, HIV was a specter haunting me and my sex life. Over time, I found ways to cope and manage the stress and risk that comes with being a promiscuous HIV-negative gay man. Perhaps the most significant step in that journey was educating myself about the actual risk of transmission, something that most gay men still don’t know enough about. If you asked a 21-year old Jake Sobo what the chances are of getting HIV after being fucked by a poz guy without a condom, I probably would have said 50%. It’s actually less than 2%, on average. And as we know now, treatment and/or PrEP virtually eliminates that risk altogether.
Getting older as a gay man almost always means that some of your friends will test positive at some point. While as many as one in four gay men overall are HIV-positive in some urban areas, that percentage jumps to over 40 percent for guys in their 40s. It sounds trite, but being friends with HIV-positive guys and realizing that their lives were basically no different from my own played a significant role in helping me reshape my understanding of the disease.
What PrEP has done for me cannot be understated. I no longer live in a world where contracting HIV seems a possible outcome that warrants my anxiety or stress. With PrEP, I can have the sex that I want, with whomever I want, without HIV looming over my decisions.
As I picked up the pieces after my last breakup, I resolved to never be in a relationship again in which I didn’t see eye-to-eye with my partner about non-monogamy and HIV risk. I’m just not built for sex with one person, and I don’t ever want to be in a situation where HIV provides the grounds for controlling my behavior. But finding another gay man as liberated from the fear of HIV seems daunting – especially living in a non-urban area. I used to think that I might never date seriously again.
But, as luck would have it, it turns out guys on PrEP aren’t the only ones who don’t fret about contracting HIV anymore.
iphone3Three dots moved silently on my iPhone screen, indicating an impending message. Finally, after what seemed like an eternity, James’ message came through. My prayer was answered.
Of course, James is a lot of things other than being HIV-positive. His serostatus turns out to be only one of so many things that I love about him. He’s goofy and ambitious. And, like me, he is a whore. We practice compersion, not jealousy; when I get my ass creamed by another guy, he doesn’t get angry. He gets turned on.
But I don’t love him despite his status, as many guys might imagine. It is not a glitch or problem or downside.  I love him, in part, because of it.
To guys out there who still don’t understand how this is possible, I invite you to look around you. The serodivide is crumbling. Hookup sites that used to allow only two options for HIVstatus now offer endless choices, from undetectable to on PrEP. Recent life expectancy projections suggest that gay men who test HIV-positive today and start treatment quickly will live longer than those who do not. Statistically speaking, my positive boyfriend is likely to outlive me.
While some friends of mine give guys who blithely refuse to fuck poz guys a pass, I don’t. You cannot hide your prejudice under the veil of risk anymore. That ship has sailed.
I know it’s not easy. Unlearning decades of stigma and fear will not happen overnight. It will take time and learning. That’s okay. But the cost of staying in place is too great, both for poz guys who face that stigma and fear on a daily basis, and to our communities which remain divided.
Tomorrow, September 27, is National Gay Men’s HIV/AIDS Awareness Day. If you’re an HIV-negative gay man and you serosort but want to do something to help end HIV stigma, take a first step. Stop serosorting. Fuck a poz guy.
Who knows, he just might be the man of your life.

1 Names have been changed.
Jake Sobo is a pen name used for anonymity. Jake has worked in the world of HIV prevention for nearly a decade. He previously published a 19-part series documenting his experiences on pre-exposure prophylaxis (PrEP), “My Life on PrEP,” for Positive Frontiers magazine, which was picked up by Manhunt, translated into French, and widely read in the HIV prevention world. He has spent the better part of his adult life having as much sex as possible while trying to avoid contracting HIV.

There is a rationale with moving forward with clinical trials. Enjoy this article!

Setbacks and Progress in the Search for an HIV Cure

Françoise Barré-Sinnousi, Sharon Lewin, and Deborah Persaud at an AIDS 2014 press conference (photo: Liz Highleyman)
Françoise Barré-Sinnousi, Sharon Lewin, and Deborah Persaud (photo: Liz Highleyman)
The quest for a cure for HIV has been one of the themes at the 20th International AIDS Conference (AIDS 2014) taking place this week in Melbourne, with scientists reporting both advances and setbacks.
Jintanat Ananworanich, formerly of the Thai Red Cross and now with the U.S. Military HIV Research Program, gave an overview of “Where Are We Now and Where Are We Going?” with cure research at an opening plenary on Monday.
After reviewing some special cases that offer proof-of-concept that it may be possible to control HIV at least temporarily without antiretroviral therapy (ART)—including the Berlin Patient, the Boston Patients, and the Mississippi Baby—she concluded that success will likely require a combination approach, for example, early ART, agents that overcome viral latency, gene therapy to protect CD4 cells from infection, and therapies that strengthen immune response.
Researchers also discussed cure-related work in oral abstract sessions at the main conference and at a two-day pre-conference “Towards an HIV Cure” symposium organized by the International AIDS Society (IAS). Several of them summarized their findings and offered their thoughts about future directions at an IAS press briefing on Monday.
Deborah Persaud from Johns Hopkins gave an update on the Mississippi Baby (now a child nearly four years old) who just before the conference was found to still have HIV after having no detectable virus while off ART for more than two years. This case suggests that HIV establishes latent reservoirs very early—the child started treatment just 30 hours after birth—and even a few remaining infected cells are enough to rekindle viral replication.
Though disappointing for the child, who has resumed antiretroviral treatment and is in good health, Persaud said, “we have learned a lot from this case and it provides a strong rationale for moving forward with a clinical trial” of very early combination therapy for infants.
Dan Barouch from Beth Israel Deaconess Medical Center described a study in monkeys, published this week in Nature, showing that an HIV-like virus seeds itself in cell and tissue reservoirs very soon after sexual exposure—even before viral load is detectable in blood plasma. Very early ART reduced the size of the reservoir, but did not prevent re-emergence of the virus after treatment was stopped. “Even very early is not early enough,” he said.
One challenge in the cure field raised by Ananworanich is that scientists—not to mention regulatory authorities, pharmaceutical companies, and HIV-positive people themselves—do not all agree about the definition of a cure. Experts increasingly agree that complete eradication of every last bit of virus may not be possible, but many people living with HIV would be happy to be able to maintain control of the virus for prolonged periods off ART.
“We’re looking at the moment at achieving long-term remission, and how long can we go [without antiretrovirals],” said AIDS 2014 co-chair Sharon Lewin from Monash University. “We’ve realized in the past year that the virus can really hang around for a very long time and pop up unexpectedly.”
One widely used strategy in HIV cure research is dubbed “kick and kill” or “shock and kill.” This involves using various methods to reactivate latent viral genetic material in resting T-cells. Once this virus “wakes up” and starts replicating, it becomes visible to the immune system and susceptible to antiretroviral drugs.
One type of agent used to reactive latent HIV is histone deacetylase (HDAC) inhibitors. HDACs are enzymes that keep DNA tightly coiled in a cell’s nucleus so it cannot be used to produce new proteins. HDAC inhibitors reverse the process, allowing viral gene expression and production of new virus.
Ole Schmeltz Søgaard (photo: Liz Highleyman)
Ole Schmeltz Søgaard (photo: Liz Highleyman)
Ole Schmeltz Søgaard from Aarhus University Hospital in Denmark described his team’s research using the HDAC inhibitor romidepsin, which is used as a treatment for lymphoma, to kick cells containing dormant HIV out of their resting state.
In a small study of six patients with long-term viral suppression on ART, romidepsin was shown to increase histone acetylation in lymphocytes, raise levels of cell-associated HIV RNA in CD4 cells, and increase plasma viral load. However, the size of the viral reservoir—as indicated by total HIV DNA in CD4 cells—did not change significantly.
“We have enough data to say the agent was successful in doing what it was supposed to: kicking virus out of cells,” Søgaard said. “We can make cells release virus into plasma, but that may not be enough to reduce the reservoir.”
Steven Deeks from the University of California at San Francisco said this first evidence that we can identify latent HIV and shock it out of hiding in people “is the single most important advance of this meeting.” That’s the shock, he said, “but once [the virus] gets out, we have to kill it.”
Like Ananworanich and most others working on HIV cure research, Deeks thinks a combination approach will be required to achieve a functional cure that allows people with HIV to remain off ART without disease progression. As the virus is released from newly activated resting cells, the immune system will need to be able to recognize and attack it.
Steven Deeks (photo: Liz Highleyman)
Steven Deeks (photo: Liz Highleyman)
“The Mississippi and Boston cases make me wonder if we will ever get rid of the entire reservoir,” Deeks said. “We may get rid of big chunk of it…but we need a way to control what’s left.”
Deeks predicted that the cure field will move in the direction of therapeutic vaccines or other immune-based therapies that can be used in combination approaches. Søgaard’s team has just started a new study looking at romidepsin in combination with the therapeutic Vacc-4x vaccine.
“We should not oppose vaccine and cure research, and probably we will need both,” predicted IAS President Françoise Barré-Sinoussi.
Liz Highleyman (liz (at) hivandhepatitis.com) is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.

Cure Research narrative. Enjoy!

Cure Research at IAS 2013

IAS2013THUMBCure research has been a mainstay of recent HIV/AIDS conferences, and the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention this month in Kuala Lumpur was no exception. While researchers presented some promising findings, the overall emphasis was on how far we are from practical and widely applicable approaches to a cure.

HIV Remission

The headline-grabbing news was a report by Timothy Henrich from Brigham and Women’s Hospital revealing that two Boston men who received bone marrow stem cell transplants to treat lymphoma had no detectable HIV at seven and 15 weeks after stopping antiretroviral therapy, or ART (abstract WELBA05).
Unlike the Berlin Patient, the Boston men did not receive stem cells from a donor with genetically resistant immune cells carrying the CCR5-delta-32 mutation, meaning they lack one of the receptors HIV uses to enter cells. The men did, however, undergo a milder pre-transplant chemotherapy regimen that enabled them to stay on ART. Once they had no signs of HIV for six months, they started an experimental treatment interruption. So far, HIV genetic material has not been detected using the most sensitive tests.
Although viral rebound typically happens within two to four weeks after ART interruption, according to lead investigator Daniel Kuritzkes, it is too soon to say these men are cured. “The virus could come back next week, after a few months, or even after a year,” Henrich told reporters.
More recently, a sobering report underlined the risk of stem cell transplantation. Hoping to replicate the Berlin Patient approach, researchers at the University of Minnesota in April performed a transplant of cord blood (which contains stem cells) from a donor with the CCR5-delta-32 mutation, in an attempt to cure an HIV-positive boy with leukemia.
Unfortunately, the university announced this week that the boy, 12-year-old Eric Blue, died in early July after developing severe graft-versus-host disease, a common complication of stem cell transplantation. Cases such as this demonstrate why stem cell transplants will not be appropriate for broad application as an HIV cure.

Early ART for Infants

Deborah Persaud (photo: Jan Brittenson)
Deborah Persaud (photo: Jan Brittenson)
Researchers are also working to replicate the success of a Mississippi baby first presented by Deborah Persaud from Johns Hopkins at this year’s Retrovirus conference. The child, whose mother did not receive drugs to prevent perinatal infection, was started on combination ART within about 30 hours after birth but was later taken off treatment by her caretakers. At a “Towards an HIV Cure” symposium prior to the IAS meeting, Persaud gave an update that the child still has no detectable virus after 15 months of follow-up off treatment.
The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group will screen infants at more than 70 sites worldwide, looking for 20 to 30 HIV-infected babies whose mothers did not receive preventive drugs or did not achieve viral suppression during pregnancy. These infants will receive a full ART regimen within 48 hours after birth, and if they show no evidence of HIV antibodies after three years on treatment, they will interrupt ART to see if they can naturally maintain viral suppression.

Routing Reservoirs

German researchers reported another case of prolonged control of HIV replication after interrupting early treatment (abstract TUPE246). This 67-year-old individual is thought to have become infected in 1999 and started triple ART within one month of seroconversion, after an acute viral illness.
After maintaining stable undetectable viral load—except for two “blips”—and a high CD4 cell count, the man elected to undergo treatment interruption in 2004. He experienced a small viral rebound, remaining below 100 copies/mL, but soon regained control of viral replication and has been undetectable ever since.
In addition to having plasma HIV RNA below the limit of detection, the man has no evidence of HIV in his cerebrospinal fluid or gut tissue, nor HIV DNA in peripheral blood mononuclear cells (PBMCs). He shows strong anti-HIV CD4 and CD8 cell responses and a normal distribution of various types of T-cells. However, virus was recovered from his CD4 cells in the laboratory using a humanized mouse model, indicating the presence of residual replication-competent HIV.
The German case joins those of 14 French patients treated during early infection, known as the VISCONTI cohort. Experts expect more such cases will come to light thanks to increased awareness of the possibility.
Antoine Cheret (photo: Liz Highleyman)
Antoine Cheret (photo: Liz Highleyman)
Antoine Chéret and fellow investigators with the French OPTIPRIM study are looking at 90 people randomly assigned to start standard three-drug ART or an intensive five-drug regimen during primary HIV infection (abstract WEAB0101). After 12 months on treatment, almost all achieved undetectable plasma HIV RNA as well as decreased HIV DNA in PBMCs, indicating a reduced viral reservoir in resting T-cells. After 24 months participants will interrupt treatment to see if they can maintain viral control like the VISCONTI patients.
Most people are not diagnosed with HIV during primary infection, but even during chronic infection, those who start treatment sooner with CD4 counts above 500 are more likely to see a reduction in their reservoir of infected cells, potentially making them better candidates for an eventual functional cure.
Laurent Houqueloux from Orléans Hospital reported that people who started ART with more than 500 cells/mm3 had reduced levels of integrated HIV DNA in PBMCs and were many times more likely to experience immune function normalization compared with those who started treatment later (abstract WEAB0102).
The Berlin Patient, the Boston stem cell patients, the German case, and the Mississippi child indicate that some individuals, under special circumstances, can achieve a functional cure that allows them to remain off treatment without disease progression for a prolonged period.
But while these examples “are exciting and give hope to patients and scientists that a cure is possible, the challenge is to understand the mechanism by which these cures have happened,” said Sharon Lewin of Monash University at an IAS press conference. “Thirty-three million people have established reservoirs, and the goal is to find out how to let them go off treatment.”
The full IAS 2013 program is available online.
Liz Highleyman (liz (at) hivandhepatitis.com) is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.

what is a cure? Interesting question, Read on please!

HIV Cure Research: Separating the Hope from the Hype

BETA-cure-update-250x150Sound science takes time. As Richard Jefferys of Treatment Action Group explained in a recent webinar, “HIV Cure Research—Getting Past the Media Hype,” a number of clinical trials are underway in the quest for an HIV cure, but none of the interventions currently under study are expected to cure people of HIV. Rather, those studies provide essential information to get cure science to “the next round” of development, said Jefferys.
Jefferys and webinar co-host David Evans, director of research advocacy at Project Inform and community advisory board member with the Delaney AIDS Research Enterprise, unpacked the concept of “cure,” outlined the types of cure currently under study, and highlighted key questions at the heart of cure research today.

Defining “Cure”

According to Evans, in cure research, “one of the biggest areas of concern is how we define a cure in the first place, and what that says about people’s hopes and desires.” So what exactly constitutes a cure, and what does “cured” look like in the real world, beyond clinical trial settings?
While acknowledging that definitions of “cure” continue to be refined, Jefferys described the most widely agreed-upon potential types:
  • A sterilizing cure would involve total elimination of all replication-competent HIV (that is, HIV that is capable of making more copies of itself) from the body.
  • With a functional cure, the virus may not have been completely eliminated but no HIV replication is detectable and individuals experience no disease progression in the absence of antiretroviral treatment.
  • Remission, the latest definition to enter the HIV cure dialog, refers to control of HIV viral load at low levels (such as below 50 copies/mL) in the absence of treatment.
Timothy Brown, who had both HIV and leukemia and underwent intensive radiation and chemotherapy and received transplanted stem cells from an HIV-resistant donor, appears to represent a sterilizing cure, Jefferys said. The most ultrasensitive tests have detected no replication-competent HIV in his tissues in the eight years since his radical treatment. (Timothy Brown tells his own amazing story here.)
However, the treatment Brown received was in itself life-threatening, and is not seen as a scalable approach to curing HIV. In addition, a sterilizing cure is the most difficult to prove, involving extensive tissue sampling and testing with the most sensitive assays to look for viral RNA, HIV’s own genetic material: “It’s a huge challenge to figure out how to measure such tiny amounts of HIV RNA,” Jefferys noted.
“We may never get to a place where we totally eradicate the virus in most people,” added David Evans, “but instead place them in a kind of remission, whereby HIV is fully controlled, but not causing much harm without the need for antiretroviral drugs.”

Current Approaches to Curing HIV

Evans detailed the current major avenues of HIV cure research, and progress to date.

“Shock and Kill”

One of the biggest obstacles to curing HIV is posed by viral reservoirs, cells harboring “latent” or non-replicating HIV. Because these latently infected cells do not display pieces of HIV on their surfaces, Evans explained, the immune system cannot not recognize and destroy them.
A handful of anti-cancer drugs belonging to a class known as histone deacetylase inhibitors (HDAC inhibitors for short) alter viral genes, allowing the body to recognize infected cells. HDAC inhibitors are being tested for their ability to force latent HIV out of hiding, then kill infected cells—a strategy known as “shock and kill.”
When researchers tested the HDAC inhibitor vorinostat (also known as SAHA) with once-daily dosing over several days, they saw a rise in viral RNA—“what we want to see,” as Evans put it, when testing a drug to shock the virus into the open. However, the increase was only temporary, and HIV DNA—the genetic material produced when HIV replicates—did not decline, indicating that no “kill” had occurred. Two clinical trials are currently underway to address the safety and efficacy of vorinostat for draining HIV reservoirs.
Another HDAC inhibitor, panobinostat, launched a media frenzy when researchers reported evidence that the drug induced HIV replication in an early-stage clinical trial; however, results on viral DNA are not yet available from the research team in Denmark, Evans stated. A trial of the HDAC inhibitor romidepsin is also underway, with results anticipated in late 2015.

Stem Cell Transplantation

The “Boston patients” made headlines in 2012, when researchers reported on two men who underwent stem cells transplant procedures similar to Timothy Brown’s, but with a few key differences: The two men had “gentler” chemotherapy and no full-body radiation, so they retained host immune system cells; they received donor cells that were susceptible to HIV infection, unlike the HIV-resistant cells Brown received; the Boston men were themselves heterozygous for the HIV-blocking mutation, meaning they each had a single copy of the protective gene; and both continued to take antiretroviral drugs throughout and following their procedures.
Up to four and a half years after the transplants, the research team could detect no HIV using highly sensitive tests, and the two individuals and the research team agreed to an analytical treatment interruption to see whether the virus would return. “Initially, things looked really good,” noted Evans in the webinar. But within weeks to months of stopping antiretroviral therapy, the virus returned. Both men saw huge spikes in their formerly undetectable viral load, Evans explained, and both experienced retroviral syndrome—the immune system’s reaction to unchecked viral replication, typically seen in people recently infected with HIV.
“I think what this is telling us is how difficult it is to actually kill the virus,” said Evans. Both men were able to get the virus under control again with antiretroviral therapy (ART).

Extremely Early Treatment

As reported previously, the “Mississippi baby” was diagnosed with HIV using RNA and DNA tests, which detect HIV’s genetic material rather than antibodies to the virus (which can be carried over from the mother). She was started on triple-drug antiretroviral treatment just 30 hours after birth, and within a month, her viral load was undetectable. She continued on treatment until around 18 months of age, when she was lost to care for several weeks. When the child was brought back for medical visits at roughly two years old, she had been off treatment for five months—yet she had an undetectable viral load.
In March 2014, when the child was approximately three years old and had been off ART for 23 months, Persaud reported at the 21st Conference on Retroviruses and Opportunistic Infections that “there has been no detectable rebound in plasma virus using standard clinical assays with detection limits of less than 20 copies/mL,” and suggested that the child is “in remission.”
Persaud also reported on a second infant, born in California, who was started on ART just four hours after delivery. HIV infection was confirmed by the same HIV RNA and DNA tests administered to the Mississippi baby. Nine months old at when Persaud reported the case, the Long Beach child had had no detectable viral RNA or DNA since day 11 and day 6 after birth, respectively. However, the child remains on ART. “These tests that we’re doing are really being done under antiretroviral treatment cover, quite unlike the Mississippi child,” Persaud said in a press conference. “Having said that, at nine months of age, there’s less than 2 copies of HIV DNA [per mL in blood cells] and we have not detected a replication-competent reservoir,” she added.
In the May 8 webinar, Evans also noted that five Canadian children born with HIV and treated within 24 hours after birth are being followed by cure researchers. All had undetectable viral load to as old as eight years of age; however, all remain on antiretroviral therapy. One child whose treatment was interrupted saw the virus return.
If most of these children are still on treatment, asked one webinar participant, why are we even talking about them? “They’re being discussed because they don’t have any detectable virus, no matter how hard we look,” explained Evans. An as Persaud put it in March, “There’s a signal here that giving very early antiretroviral drug treatment in neonates really restricts HIV spread [in the body], to the point that it becomes difficult to detect infection.”
Also as previously reported, the VISCONTI Cohort in France includes adults who began ART within days to weeks after infection with HIV, remained on treatment for several years with undetectable viral load, and have now been off ART for as long as ten years with no major viral rebound.
As Evans emphasized, these individuals are genetically distinct from “elite controllers”—a small population of people whose immune systems are able to keep HIV in check without treatment. The cohort originally included 14 individuals, but Evans noted that roughly 20 are being followed today.

Key Questions

Cure trials to date have provided essential data that point the way for future research. However, as Richard Jefferys explained, many significant questions remain that have important implications for the way we pursue cure science.
For example, we know draining viral reservoirs is key—but by how much? “How much do you have to reduce the HIV reservoir to really have an effect, and not have it return off antiretroviral treatment?” asked Jefferys. Long-term monitoring of trial volunteers will be essential as more studies tackle viral reservoirs.
Other major questions highlighted in the webinar included:
  • Can combinations of interventions be used to reverse HIV latency and eliminate infected cells?
  • Are there immune responses that can be induced or revived that would lead to HIV control?
  • Can gene therapies generate enough HIV-resistant cells to cure infection?
  • Can early treatment lead to a cure in more children? In adults? And how early is early enough?
  • How and when can we confidently deem a person “cured”?
To explore these and other questions, Jefferys added, the Forum for Collaborative HIV Research will host a public meeting on June 17 in Washington, DC. The meeting will be webcast to allow for greater participation; click here for details and to register.
The webinar concluded with a thought-provoking Q&A session, in which one participant questioned the wisdom of funneling limited resources into cure research rather than expanding access to HIV treatment. “As good as antiretroviral therapy is, and as close as we are getting people to a place where they would live out a natural, normal life span, we still do see long-term toxicities and health concerns because of that low level of virus that is able to persist,” stated Evans. A scalable cure or way to get people into HIV remission in the absence of ART, he said, would be “a net win for all.”

Therapy Clinical Trials is a good subject I am sharing with you here. I enjoyed the article. Enjoy too!

Ask a Guinea Pig: Gene Therapy Clinical Trials—If and When

When I first became involved in AIDS treatment activism, many of us felt that the focus of HIV therapy should be the immune system—the target of HIV—rather than the virus. Yet knowledge of the immune system was more limited than it is today, and finding the best place to target our own host defense mechanism was, and still is, a huge challenge.
Today, however, with the understanding that the CCR5 protein on the surface of CD4 cells is an important receptor for HIV to latch onto, scientists have reached the place and time where clinical trials can now be performed with gene therapy technology that can render a person’s own CD4 cells resistant to HIV. This is one way to target our own genetic blueprint with the ultimate goal of stopping AIDS.
People with a unique genetic variation called CCR5-delta-32 lack functional CCR5 on their CD4 cells, rendering them virtually immune to HIV. Piggybacking on this discovery, researchers first developed drug treatments that target the CCR5 coreceptor itself, such as the already approved HIV medication maraviroc (Selzentry) and the experimental drug cenicriviroc. For gene therapy as an HIV cure strategy, proof of concept came when a stem cell transplant from a donor with the CCR5-delta-32 variation cured “Berlin Patient” Timothy Ray Brown of his HIV infection. (Stem cell transplants are also showing positive results in two Boston men diagnosed with HIV and cancer.)
Now there are multiple gene therapy technologies that employ different mechanisms to block the gene for CCR5. The difference between these approaches and CCR5-blocking drugs is that hopefully gene therapy treatment can be given just once or twice, whereas drug treatment equals daily medication for life. The strategy for a “functional cure” is to enable our bodies to keep HIV under control and stop daily antiretroviral therapy—which, although it has been lifesaving for millions of people, can have short- and long-term toxicity issues and is simply not sustainable to universally treat HIV globally.
Furthest along in development is Sangamo Biosciences’ zinc finger nuclease technology (SB-728). I was the second person to enroll in the Phase 1 clinical trial, the first HIV gene therapy trial to show success. After one year, safety was established and improvements in CD4 counts were sustained. (Read a summary of recent SB-728 results here.)
As reported earlier this month at the 16th Annual Meeting of the American Society of Gene and Cell Therapy, genetically modified transitional memory cells—a particular type of CD4 cell—were reconstituted and maintained following infusion into HIV-positive volunteers. This means that this particular gene therapy product may slow HIV disease progression in long-term HIV-positive individuals.
So the question is not if gene therapy for HIV will be safe and effective but when it will become a strategy towards a functional cure.
But the row has to be hoed, so to speak: Some approaches are still in animal studies, and there is a long way to go to prove gene therapy is not only safe and effective in raising CD4 cell counts and suppressing HIV in humans but that this approach can also functionally cure HIV infection. And enrollment in a gene therapy clinical trial likely brings bigger challenges than for drug trials. There may be risks involved in disrupting our own genes, in delivering the gene therapy to its target, and in the blood processing involved. Long-term safety has not been established, and there are considerable unknowns down the road.
That said, unless and until researchers can study gene therapy approaches with actual participants living with HIV, we may never get to a “functional cure” or even improvements upon how HIV is treated today. With HIV gene therapy research ramping up, there will be a need for many people who may be feeling just fine right now to participate in potentially risky studies. So stay tuned, get informed, and get involved!

Resources for the Trial-Curious

Take advantage of these online resources to learn about the potential perks and challenges of joining a clinical trial and to see what studies are enrolling near you.
  • ClinicalTrials.gov: A searchable database of most U.S. clinical trials, with in-depth descriptions of each study.
  • Volunteering in a Clinical Trial: A user-friendly guide to participating in clinical research, from Centerwatch. Read it online or download and print the brochure to take along on your study visits.
  • Guide to Clinical Trials for People with Hepatitis C: It’s not just about hep C! Download this information-packed, reader-friendly guide to learn how clinical trials work and what key questions to ask the research team before joining a trial.
  • HIVresource: This free quarterly newsletter from San Francisco AIDS Foundation links readers with HIV-related clinical trials  in the San Francisco Bay Area.

Selected Sources

June, C. and others. Induction of acquired CCR5 deficiency with zinc finger nuclease-modified autologous CD4 T cells (SB-728-T) correlates with increases in CD4 count and effects on viral load in HIV-infected subjects. 19th Conference on Retroviruses and Opportunistic Infections. Seattle. March 5–8, 2012. Abstract 155.
Lee, G. and others. Long term CD4 reconstitution in HIV subjects receiving ZFN CCR5 modified CD4 T-cells (SB-728-T) may be attributed to the sustained durability of the central memory T-cell subset. 16th Annual Meeting of the American Society of Gene and Cell Therapy. Salt Lake City. May 15–18, 2013. Abstract 58.

I came across this wonderful article on "undetectable" and "negative" as far as HIV goes. I want to share it with you!

“Undetectable”: Your Burning Questions Answered

Dr. Joanna Eveland
Dr. Joanna Eveland (photo: Liz Highleyman)
Last month, we asked for your burning questions about “undetectable” viral load. Thanks to everyone who posted a question! We enlisted Dr. Joanna Eveland of Mission Neighborhood Health Center to answer your questions about what “undetectable” means for your health and for your sex partners.

Can I still transmit HIV if my viral load is undetectable?

“Undetectable” and “HIV-negative” are not the same thing. Having undetectable viral load does dramatically decrease the odds of transmitting the virus, but it doesn’t eliminate it.
What does the science say? Watch this video to see how lower viral load translates to lower risk of passing on HIV.
Viral load is the amount of virus that is measured in the blood at one point in time. The test result you see at your doctor’s appointment today tells you what your viral load was a few weeks ago, when you got your blood drawn. If you continued taking your antiretroviral medicines daily, your viral load is probably still undetectable, but not necessarily.
Taking even a brief break from your meds can increase your viral load, as can having another illness like the flu or a sexually transmitted infection (STI). It’s also good to note that viral load in the blood is not necessarily the same as viral load in semen.

If I’m undetectable, do I still need to use condoms?

The decision to use condoms or not is ultimately between you and your partner. It’s important to discuss together what the health concerns might be for the two of you, and to be comfortable with your decision.
Things to think about and discuss with your partner(s) may include whether or not you have other sex partners, how frequently you get tested for other STIs, how adherent you are to your HIV meds, and how important (or not) using condoms is to you. Weighing the health concerns alongside the physical and emotional components will help you strike the right balance with your partner about “risks” and pleasure. While being undetectable is a great thing for your health, it doesn’t protect you against other STIs or offer an HIV-negative partner 100% protection against contracting HIV.

How can I tell if someone is undetectable?

You cannot “tell” if someone is undetectable just by looking at them; viral load is determined by tests that measure the amount of virus in a person’s blood. It’s just like how you can’t tell if someone is HIV positive.

If my viral load is undetectable, can I stop taking my meds?

No, you should NOT stop taking your meds. One of the main goals of taking HIV meds is to stop the virus from replicating (making more copies of itself) inside your body. If your viral load is undetectable, it means your HIV meds are working and you should definitely continue taking them. If you stop taking your meds, then HIV will resume its attack on your immune system and your health may worsen.
In the past, treatment interruptions or “drug holidays” were sometimes recommended because of concerns about medication toxicity, but HIV medications today are much safer and better tolerated. Also, we now know that untreated HIV is toxic to every system in the body, and that people who stay on continuous treatment (until we have a cure) have a lower risk of dying—not just from an HIV-related infection, but from a heart attack or cancer.

If the virus is undetectable in my blood, is it undetectable in my semen?

As you know, HIV can be found in both blood and semen. It’s important to remember that the amount of HIV in these bodily fluids differs. Research shows that HIV can sometimes be detected in semen even when viral load is undetectable in blood. Even if the viral load in your semen is at low levels, there may be chance that HIV can be transmitted to your partner. We do not yet know how much virus needs to be present in genital fluids for transmission to be possible.

Is it possible to become undetectable if I am not on HIV meds?

Most people have to take HIV meds to control the virus and become undetectable. About 1 in 300 people keep their viral load undetectable without taking medications. These individuals are called “elite controllers.”
Also, about 5% of HIV-positive people maintain healthy CD4 T-cell counts for at least ten years despite not having an undetectable viral load. People in this category are called “long term non-progressors.” We’re still learning what factors in a person’s immune system or in the virus lead to this phenomenon. It may be that some people’s immune systems are stronger at fighting the virus. It may be that the virus itself is weaker. If we understand how this works, we’re closer to a cure for HIV.

If I get an STI, can my viral load go up?

Yes, getting infected with an STI—or any other infection, like the flu—can cause an increase in your viral load.

If both my partner and I are undetectable, can we not use condoms?

If you’re both positive and want to stop using condoms, the research indicates that re-infection or super-infection is rare and the risk is greatly reduced for men who have longstanding (more than three years) HIV infection. For guys who got HIV more recently (less than three years), the research indicates that continued condom use may be a benefit.
Even if re-infection with HIV is not a concern, other STIs such as syphilis and gonorrhea can be. Having STIs can increase your viral load, not to mention that you can continue to re-infect your partner with an STI if you are not aware of it and don’t get treated. We’re also seeing more cases of hepatitis C being sexually transmitted, especially among HIV-positive gay men.
It’s important to talk with your partner about whether you have an “open relationship” and have sex with other partners. It’s also important to periodically revisit conversations about your sexual relationship. Some couples don’t revisit these conversations, only to find out that the original agreement may not have been maintained by both partners over time.

If I’m undetectable, does that mean I don’t have the virus anymore?

If you are undetectable, it means that the amount of HIV in your bloodstream is in low enough amounts that it is not detectable in your routine labs. It means you know your HIV status and are getting the HIV treatment and care you need to lead a healthy life. It does not mean that the virus has disappeared from your body.
The definition of undetectable has changed as our lab tests have gotten better. We used say someone was undetectable if they had less than a thousand copies of virus in a milliliter of blood. Today’s more sensitive tests can detect as low as 10–20 copies of virus in a sample.
Being undetectable isn’t a cure for HIV; current medications only go after HIV that is actively replicating, and some non-replicating virus hides inside our cells, unharmed by medications.

I heard that studies with straight couples showed that being on HIV meds reduced the chance of transmitting HIV by 92%–96%. Does this statistic hold true for gay couples, too?

Two studies compared HIV transmission in mostly heterosexual couples where the HIV-positive partner either started HIV treatment or delayed treatment; they found a 92%–96% reduction in HIV transmission risk when the HIV-positive partners started antiretroviral treatment.
These studies were done mostly with heterosexual couples; we’re not sure if the same findings apply to gay men, who may have different biological risk factors than straight couples (e.g., more anal sex vs. vaginal sex). Other factors, such as whether one or both partners has an STI, also affect the risk of HIV transmission.

How long do I need to be on ART before my viral load becomes undetectable?

It depends primarily on what your viral load was before you started medications (more virus present means it takes more time to reduce viral load). Your T-cell count, general health, and whether you’ve been on treatment before also play a role.
The goal is that pretty much everybody should have an undetectable viral load after 16–24 weeks with appropriate treatment. If your viral load is not decreasing appropriately, your provider should check to make sure that you’re taking the medicines as directed, that you’re absorbing enough of them, and that you’re not resistant to them. Talking frankly about whether you’re taking the medicines, any bad side effects you have, and any other medicines, supplements, or recreational drugs you are using will help you get to undetectable faster.
Get an HIV pharmacist’s tried-and-true tips and strategies for getting to undetectable viral load—and staying there.
Once you achieve an undetectable viral load, you’ll still need to get blood tests at least every six months to make sure that the medicines continue to work and don’t have any negative effects on your body. This is an essential part of keeping your virus in check and staying healthy with HIV.

PrEP and PEP, easily explained in this article, Enjoy!

Fact Sheet: PrEP and PEP

PillsCascade500Looking for basic facts about PrEP and PEP—and the difference between the two? Start here for some simple and straightforward definitions of key terms that come up frequently when talking about PrEP and PEP, as well as a run-down of the science behind PrEP and a few things to know about this new HIV prevention tool.

Key Terms

  • PrEP: Short for “pre-exposure prophylaxis,” PrEP is an HIV prevention strategy in which HIV-negative people take an oral pill once a day before coming into contact with HIV to reduce their risk of HIV infection. PrEP must be taken for at least 7 days to reach optimal levels of protection against HIV.
  • PEP: Short for “post-exposure prophylaxis,” PEP is an HIV prevention strategy in which HIV-negative people take anti-HIV medications after coming into contact with HIV to reduce their risk of HIV infection. PEP must be started within 72 hours after HIV exposure.
  • Condoms: A type of barrier used during sex. “Male” condoms are worn over the penis, and “female” condoms can be worn inside the vagina or rectum. Condoms are the only tool that protects against both HIV, certain sexually transmitted infections (STIs), and pregnancy when used correctly and consistently.
  • Truvada: This brand-name drug combines tenofovir (Viread) and emtricitabine (Emtriva) into one pill and is made by Gilead Sciences. It has been used by HIV-positive people to treat HIV disease since 2004, and currently is the only pill approved for PrEP for HIV-negative people.
  • Adherence: The degree to which an individual takes a medication regularly as prescribed. For HIV-negative people, not taking PrEP daily can lead to increased risk for HIV infection. (Check out these tried-and-true tips and resources to boost adherence.)
  • HIV antibody test: A type of HIV test that checks a blood or oral fluid sample for antibodies against HIV. Because the body does not begin producing antibodies for two weeks or longer, an antibody test will not reliably detect a recent (acute) HIV infection. Several community-based clinics offer HIV antibody tests that offer results the same day.
  • HIV RNA test: Different from an antibody HIV test, this test looks for the presence of the actual virus in the blood and can detect if someone has acute HIV infection. In order to determine if someone is eligible for PrEP, a medical provider must confirm the individual is actually HIV negative. There are currently no HIV RNA tests approved by the FDA that offer same-day results.
  • Clinical trial: A medical study to determine whether a new drug or drug combination, assay, device, or procedure is safe and/or effective. To learn more about the clinical trial process and different clinical trial phases, click here.
  • Placebo: To help determine whether a new drug or tool is effective, participants in a clinical trial will be assigned to take either the drug or tool being studied or a placebo, which contains no drug. For example, in studies of oral PrEP, the placebo was a sugar pill. The group of participants who receive the placebo is the “control arm” of the study.
  • Demonstration project: After a drug has been deemed safe and effective through clinical trials, a demonstration project is meant to figure out how to best deliver and use the new drug or tool in a real-world setting.
  • Bone mineral density: A measure of how much calcium and other minerals are present in bone tissue. With Truvada for PrEP, 1 in 100 people will experience decreasing bone mineral density issues, which go away once drug is stopped.
  • Creatinine clearance: An indicator of kidney health that is monitored by medical providers for individuals taking PrEP. With Truvada for PrEP, 1 in 200 people will have kidney problems with mild increases in serum creatinine, which go away once the drug is stopped.

The Science Around PrEP

  • iPrEx Study: An international study involving nearly 2,500 sexually active, HIV-negative gay and bi men and trans women in six countries for nearly two years. The iPrEx trial that found people who were randomly assigned to receive Truvada had a 44% overall reduction in HIV risk compared with those who received placebo; however, this group included people who were offered PrEP but chose not to take it. For people who actually took PrEP regularly, HIV risk was reduced by more than 90%.
  • Partners PrEP: An international study involving more than 4,500 heterosexual men and women in Kenya and Uganda who were in couples where one partner was HIV positive and the other was HIV negative (what scientists call “serodiscordant” couples). Partners PrEP found people who were assigned to receive Truvada had up to 75% reduction in HIV risk compared with the placebo group. Among people who had detectable levels of Truvada in their blood, HIV risk was reduced by at least 90%.
  • TDF-2: An international study involving more than 1,200 heterosexual men and women in Botswana who were in serodiscordant couples (similar to Partners PrEP) that found people who were assigned to receive Truvada had up to 62% reduction in HIV risk compared with placebo.
  • Fem-PrEP: An international study involving over 2,100 women in Kenya, South Africa, and Tanzania that was stopped early because there was no difference in new HIV infections between those assigned to take Truvada or placebo. A later look at drug blood levels found that most of the women assigned to take PrEP did not take it as recommended. Adherence was too low to detect any protective effect.*
  • VOICE (Vaginal and Oral Interventions to Control the Epidemic): An international study involving more than 5,000 women in South Africa, Uganda, and Zimbabwe, in which participants were randomized to use one of the following products daily: tenofovir gel, placebo gel, oral tenofovir tablet, oral Truvada, or an oral placebo pill. All study arms were stopped because none of the products were found to prevent HIV infection in the trial. A later look at drug blood levels found that most of the women did not actually use the study drugs.*
  • Bangkok Tenofovir Study: An international study involving more than 2,400 people who reported injecting drugs during the previous year in Bangkok, Thailand, that found people who were assigned to receive Truvada had nearly 49% reduction in HIV risk compared to placebo. Of the people who had detectable levels of Truvada in their blood, HIV risk was reduced by 74%. As yet, it is unclear whether PrEP prevented HIV acquisition via sex or shared needles.
*Given the Fem-PrEP and VOICE results, researchers are trying to figure out the social and behavioral factors that play out in HIV prevention trials, beyond whether the medications themselves work. Age, marital status, competing needs, HIV stigma, perceptions about HIV risk, and beliefs and attitudes about taking pills and prophylactic drugs are all factors to consider in understanding why this type of prevention strategy was not a good fit for women in the communities where these studies took place.

Things to Keep in Mind

  • Only people who are HIV negative should use PrEP or PEP.
  • You must be tested for HIV and have a documented negative test result before starting PrEP.
  • PrEP and PEP are available by prescription from a medical provider, such as a physician, nurse practitioner, or physician assistant. You can also get PEP at your local emergency room or urgent care clinic, although these locations may provide just the first two or three days’ doses to get you started (for example, until your medical provider’s office reopens on a weekday). You will need to talk with your provider to see if PrEP or PEP is right for you.
  • PrEP is more than just taking a pill every day; it also involves frequent medical visits and lab tests to check for HIV, other STIs, and any changes in kidney health.
  • Neither PrEP nor PEP protects against other STIs or pregnancy, and they are not cures for HIV.
  • PEP is taken for 28 days.
  • PrEP does not have to be taken forever and can be stopped at any time under the supervision of your medical provider. When stopping PrEP, individuals should continue using it for four weeks after the last significant exposure.
  • If you’ve used PEP in the last year, it might be a good idea to talk to your medical provider about PrEP.
  • Curious about how to access PrEP or PEP in your community? Most private health insurance plans, as well as Medicaid, cover the cost of Truvada for PrEP. If you have specific questions, check here for answers.
A question that often comes up when talking about PrEP is “What about condoms?” For people who do not use condoms every time they have sex, PrEP provides an effective layer of protection against HIV. The choice to use PrEP, like the choice to use condoms, is a personal decision. The important thing is to find an HIV prevention strategy that fits your needs and meets your sexual health goals.
Megan Canon, MPH, is the social marketing manager for San Francisco AIDS Foundation and the founder of PrEPfacts.org.

Enjoy this article on the narrative around cure of HIV.

HIV Cure Research: Separating the Hope from the Hype

BETA-cure-update-250x150Sound science takes time. As Richard Jefferys of Treatment Action Group explained in a recent webinar, “HIV Cure Research—Getting Past the Media Hype,” a number of clinical trials are underway in the quest for an HIV cure, but none of the interventions currently under study are expected to cure people of HIV. Rather, those studies provide essential information to get cure science to “the next round” of development, said Jefferys.
Jefferys and webinar co-host David Evans, director of research advocacy at Project Inform and community advisory board member with the Delaney AIDS Research Enterprise, unpacked the concept of “cure,” outlined the types of cure currently under study, and highlighted key questions at the heart of cure research today.

Defining “Cure”

According to Evans, in cure research, “one of the biggest areas of concern is how we define a cure in the first place, and what that says about people’s hopes and desires.” So what exactly constitutes a cure, and what does “cured” look like in the real world, beyond clinical trial settings?
While acknowledging that definitions of “cure” continue to be refined, Jefferys described the most widely agreed-upon potential types:
  • A sterilizing cure would involve total elimination of all replication-competent HIV (that is, HIV that is capable of making more copies of itself) from the body.
  • With a functional cure, the virus may not have been completely eliminated but no HIV replication is detectable and individuals experience no disease progression in the absence of antiretroviral treatment.
  • Remission, the latest definition to enter the HIV cure dialog, refers to control of HIV viral load at low levels (such as below 50 copies/mL) in the absence of treatment.
Timothy Brown, who had both HIV and leukemia and underwent intensive radiation and chemotherapy and received transplanted stem cells from an HIV-resistant donor, appears to represent a sterilizing cure, Jefferys said. The most ultrasensitive tests have detected no replication-competent HIV in his tissues in the eight years since his radical treatment. (Timothy Brown tells his own amazing story here.)
However, the treatment Brown received was in itself life-threatening, and is not seen as a scalable approach to curing HIV. In addition, a sterilizing cure is the most difficult to prove, involving extensive tissue sampling and testing with the most sensitive assays to look for viral RNA, HIV’s own genetic material: “It’s a huge challenge to figure out how to measure such tiny amounts of HIV RNA,” Jefferys noted.
“We may never get to a place where we totally eradicate the virus in most people,” added David Evans, “but instead place them in a kind of remission, whereby HIV is fully controlled, but not causing much harm without the need for antiretroviral drugs.”

Current Approaches to Curing HIV

Evans detailed the current major avenues of HIV cure research, and progress to date.

“Shock and Kill”

One of the biggest obstacles to curing HIV is posed by viral reservoirs, cells harboring “latent” or non-replicating HIV. Because these latently infected cells do not display pieces of HIV on their surfaces, Evans explained, the immune system cannot not recognize and destroy them.
A handful of anti-cancer drugs belonging to a class known as histone deacetylase inhibitors (HDAC inhibitors for short) alter viral genes, allowing the body to recognize infected cells. HDAC inhibitors are being tested for their ability to force latent HIV out of hiding, then kill infected cells—a strategy known as “shock and kill.”
When researchers tested the HDAC inhibitor vorinostat (also known as SAHA) with once-daily dosing over several days, they saw a rise in viral RNA—“what we want to see,” as Evans put it, when testing a drug to shock the virus into the open. However, the increase was only temporary, and HIV DNA—the genetic material produced when HIV replicates—did not decline, indicating that no “kill” had occurred. Two clinical trials are currently underway to address the safety and efficacy of vorinostat for draining HIV reservoirs.
Another HDAC inhibitor, panobinostat, launched a media frenzy when researchers reported evidence that the drug induced HIV replication in an early-stage clinical trial; however, results on viral DNA are not yet available from the research team in Denmark, Evans stated. A trial of the HDAC inhibitor romidepsin is also underway, with results anticipated in late 2015.

Stem Cell Transplantation

The “Boston patients” made headlines in 2012, when researchers reported on two men who underwent stem cells transplant procedures similar to Timothy Brown’s, but with a few key differences: The two men had “gentler” chemotherapy and no full-body radiation, so they retained host immune system cells; they received donor cells that were susceptible to HIV infection, unlike the HIV-resistant cells Brown received; the Boston men were themselves heterozygous for the HIV-blocking mutation, meaning they each had a single copy of the protective gene; and both continued to take antiretroviral drugs throughout and following their procedures.
Up to four and a half years after the transplants, the research team could detect no HIV using highly sensitive tests, and the two individuals and the research team agreed to an analytical treatment interruption to see whether the virus would return. “Initially, things looked really good,” noted Evans in the webinar. But within weeks to months of stopping antiretroviral therapy, the virus returned. Both men saw huge spikes in their formerly undetectable viral load, Evans explained, and both experienced retroviral syndrome—the immune system’s reaction to unchecked viral replication, typically seen in people recently infected with HIV.
“I think what this is telling us is how difficult it is to actually kill the virus,” said Evans. Both men were able to get the virus under control again with antiretroviral therapy (ART).

Extremely Early Treatment

As reported previously, the “Mississippi baby” was diagnosed with HIV using RNA and DNA tests, which detect HIV’s genetic material rather than antibodies to the virus (which can be carried over from the mother). She was started on triple-drug antiretroviral treatment just 30 hours after birth, and within a month, her viral load was undetectable. She continued on treatment until around 18 months of age, when she was lost to care for several weeks. When the child was brought back for medical visits at roughly two years old, she had been off treatment for five months—yet she had an undetectable viral load.
In March 2014, when the child was approximately three years old and had been off ART for 23 months, Persaud reported at the 21st Conference on Retroviruses and Opportunistic Infections that “there has been no detectable rebound in plasma virus using standard clinical assays with detection limits of less than 20 copies/mL,” and suggested that the child is “in remission.”
Persaud also reported on a second infant, born in California, who was started on ART just four hours after delivery. HIV infection was confirmed by the same HIV RNA and DNA tests administered to the Mississippi baby. Nine months old at when Persaud reported the case, the Long Beach child had had no detectable viral RNA or DNA since day 11 and day 6 after birth, respectively. However, the child remains on ART. “These tests that we’re doing are really being done under antiretroviral treatment cover, quite unlike the Mississippi child,” Persaud said in a press conference. “Having said that, at nine months of age, there’s less than 2 copies of HIV DNA [per mL in blood cells] and we have not detected a replication-competent reservoir,” she added.
In the May 8 webinar, Evans also noted that five Canadian children born with HIV and treated within 24 hours after birth are being followed by cure researchers. All had undetectable viral load to as old as eight years of age; however, all remain on antiretroviral therapy. One child whose treatment was interrupted saw the virus return.
If most of these children are still on treatment, asked one webinar participant, why are we even talking about them? “They’re being discussed because they don’t have any detectable virus, no matter how hard we look,” explained Evans. An as Persaud put it in March, “There’s a signal here that giving very early antiretroviral drug treatment in neonates really restricts HIV spread [in the body], to the point that it becomes difficult to detect infection.”
Also as previously reported, the VISCONTI Cohort in France includes adults who began ART within days to weeks after infection with HIV, remained on treatment for several years with undetectable viral load, and have now been off ART for as long as ten years with no major viral rebound.
As Evans emphasized, these individuals are genetically distinct from “elite controllers”—a small population of people whose immune systems are able to keep HIV in check without treatment. The cohort originally included 14 individuals, but Evans noted that roughly 20 are being followed today.

Key Questions

Cure trials to date have provided essential data that point the way for future research. However, as Richard Jefferys explained, many significant questions remain that have important implications for the way we pursue cure science.
For example, we know draining viral reservoirs is key—but by how much? “How much do you have to reduce the HIV reservoir to really have an effect, and not have it return off antiretroviral treatment?” asked Jefferys. Long-term monitoring of trial volunteers will be essential as more studies tackle viral reservoirs.
Other major questions highlighted in the webinar included:
  • Can combinations of interventions be used to reverse HIV latency and eliminate infected cells?
  • Are there immune responses that can be induced or revived that would lead to HIV control?
  • Can gene therapies generate enough HIV-resistant cells to cure infection?
  • Can early treatment lead to a cure in more children? In adults? And how early is early enough?
  • How and when can we confidently deem a person “cured”?
To explore these and other questions, Jefferys added, the Forum for Collaborative HIV Research will host a public meeting on June 17 in Washington, DC. The meeting will be webcast to allow for greater participation; click here for details and to register.
The webinar concluded with a thought-provoking Q&A session, in which one participant questioned the wisdom of funneling limited resources into cure research rather than expanding access to HIV treatment. “As good as antiretroviral therapy is, and as close as we are getting people to a place where they would live out a natural, normal life span, we still do see long-term toxicities and health concerns because of that low level of virus that is able to persist,” stated Evans. A scalable cure or way to get people into HIV remission in the absence of ART, he said, would be “a net win for all.”