Wednesday, 25 March 2015

Targeting Africans and recent Immigrants from Africa living in the Bay Area (West Coast of USA)



Targeting Africans and recent immigrants from Africa living in Bay Area.

1.0     ABSTRACT
This concept note is about Africans and recent immigrants from Africa (from here on referred to as beneficiaries) in the West Coast Bay Area. It is also about how best they can be involved in owning skills for health living and outcomes in USA. In 2012, a friend knocked on our door, her roommate was having a baby. This was in Los Angeles CA. It was 2:00 am. We rushed her to a hospital which we had googled and fortunately was 15 minutes away. She did not have insurance, we collected money towards that. She was admitted and delivered a bouncing baby girl. The previous week, we had helped another person who had chest pain. We prevailed on him to go to the hospital. This was a saving moment for him. He was diagnosed with a buildup of fluid in the pleural space. A month before I had talked to a friend who was complaining of frequent micturition, thirst and frequent fatigue after simple daily activities. I escorted her to Hospital and she was diagnosed with Diabetes. In Boston MA, a friend continued complaining of stomach pain and she could point it out in the right lower quadrant. It turned out she had appendicitis, a diagnosis arrived at after we rushed her to Hospital. A mother was overwhelmed by developmental delays of her son. She even relocated for fear of stigma among the African communities that had embraced her on arrival in USA. But, counseling and reassurance enabled her overcome her own fears and she is now a strong advocate in her area for children with disabilities. A doctor and mother to a daughter who had sickle cell disease never gave up seeking treatment for the daughter. The family went through all the processes of an autologous bone marrow transplant, the daughter is now free of sickle cells. I[1] have attended many African community, cultural and social events[2] as part of my own understanding of other Africans, how they socialize and also as an appraisal, the precursor for starting a dedicated healthy living support platform. As a volunteer and Trustee with the African Empowered Communities-USA[3], we reach out to Africans new in USA and engage them in activities that increase awareness, world view, cultural sensitivity and utilization of the service delivery systems in USA. The goal being full utilization and full integration. There are patterns through which beneficiaries can be mobilized, empowered to become fully involved participants in healthy living. This tool is a mobilization tool tailored for Africans new in America. It can be copied for other immigrant communities too. It is based on Using Community or Social Events (UCEs/USEs) to continue mobilizing beneficiaries of healthy living in USA. On outcome is making health, nutrition and a quality life part of their plans[4].

The Executive Summary:
I have interacted with Africans and recent immigrants from Africa in the Bay area for one full year. Anecdotal information estimates give about 20,000 Africans and recent immigrants from Africa above 21 years live in the entire Bay Area. In presenting this note I hope to reach out to whoever can support my desire for promoting practices that in turn improve on quality of life, mental-health and nutrition of beneficiaries (whose population estimation was arrived at anecdotally)[5].
The concept note is divided into the following sections: 1.0   Abstract is a short narrative and introduction 1.1, Background, shows who the beneficiaries are, attempts a social diagnosis and then shows activities geared at obtaining healthy outcomes. It further introduces opportunities where diet, play and mental health are integrated in beneficiary daily, community and social events. 1.2. Goal, 1.3 introduces the Management plan, 2.0. Shows how Using Community or Social Events (UCEs/USEs) to continue mobilizing beneficiaries of health services, 2.1. Description, 2.1.1 Long Term Objective, 2.1.2. Short Term Objective, 2.2. Problem Statement and Justification, 2.3. Proposed Interventions /Solutions, 3.0      Project Technical Approach / Activities, 3.1. The following are the aspirations, 4.0. Monitoring and Evaluation, 5.0 Sustainability.
1.1     Background and Diagnosis:
Innovative ways to get beneficiaries to access the life improving health services in their vicinities[6] can be explored. Cause and effect scenarios play a major role on decisions to place importance on health or prioritize it. Responses as to attendance are placed in three categories whose acronym is CAT. C for chasing; A for aversion; T for tenacity.
Chasing papers and documentation requirements, chasing the dollar to pay bills and chasing an ‘Americanness’ embracing and pursuing happiness in the present, replacing receding nostalgia. In other words, doing away with old life!
There is an aversion for hospitals which in their psyche are places of doom; anecdotal feedback is resplendent with conversations alluding to lengthy procedures and invasiveness; many deliberately turn away or dislike healthy living patterns that take them away from set ways; many have ingrained tabooist tendencies that affect placing trust in health systems and providers. Such remarks like “I cannot undress before ‘them’ are common.”
Tenacity is explained by belief in that African perpetual virility, invincibility and a post arrival shock. The belief is that of an African who arrived when many years of socialization have rewarded a healthy life, weight gain and longevity. That inertia becomes the survival closet or locker whose access is only open to an owner. Past deeply held beliefs and ways that enabled one to navigate life in Africa are now questioned through apparent stories of consequences of reckless lifestyles around diet, play and mental-health. But all is not gloom and dire straits!
The following can be the opportunities:
1.     To establish a resource and drop-in center as a static facility to conduct activities geared at entrenching good Diet, Play and Mental Health (DPM) living practices. Themes will be linked with International days of celebration, religious festivity days and other social-cultural events[7].
2.     To design, develop and maintain a website with updated tips and information on healthy living targeting Africans new in America. The website will be a portal highlighting African community events and activities e.g. Moroccan, Zimbabwean, Angolan, Senegalese, Ivorian, Gambian, Ghanaian, Ugandan, South African, Cape Verdean, Swazi, Lesotho and Kenyan. The website has the advantage of anonymous information sharing and as an interactive social media tool.
3.     To develop a schedule to promote and engage beneficiaries in conscietization and owning of good Diet, Play and Mental-Health (DPM) practices[8]. This will use informal and formal meetings as means of guiding conversation and decisions to adopt healthy living lifestyles. Households will be encouraged to engage in such activities like ‘game nights.’ It will then be possible to start healthy living conversations or even continue with them.
4.     Develop a yellow pages pull out with addresses and locations where beneficiaries can meet, socialize and start or continue conversations around diet, play and mental health living. The pull out will be a hard copy used as a desk reference tool.
5.     Link up with service providers and solicit for space, time and tailored opportunities to increase beneficiary conscientious utilizing of services. Such spaces will be booked at gyms, cinemas, recreation parks and other venues[9].
6.     Develop the “drums-and-fire” networks to check on or support each other as part of adherence and decision support mechanisms. This will tap into contacts’ lists as well as a list-serve. This will also employ another mobilization tool among Africans called the “ear-to-the-ground.” This derives from ancient African ways of sharing information[10]. Info-blasts will be maintained through the list-serve, elders of communities, religious leaders and social media platforms.
7.     Involve Africans in extravaganza activities focusing on health with the support of Certified Therapeutic Recreation Specialists (CTRS), social workers and counselors. It is hoped that retreats, camps and seminars focusing on knowledge sharing will be the main activities. These will integrate events recognizing elders and leaders who have helped beneficiaries to embrace and adhere to healthy living practices.
1.2     The Diet, Play and Mental-Health (DPM) goals:
To engage beneficiaries in activities that help them achieve physical, cognitive, social empowerment and skills through participation. The target area is San Francisco, Oakland, Brisbane, Richmond, Concord, Colma, Treasure Island, Daly City, South San Francisco and San Jose. Africans have established entertainment, food art, sport, residences, businesses and networks in these areas. It is these spaces that will be tapped into.
1.3     Tentative Community Liaison:
Thomas Rogers Muyunga Mukasa is the lead and reporting focal person.
2.0 Using Community or Social Events (UCEs/USEs) to continue mobilizing beneficiaries of health services:
2.1. Description
2.1.1  Long Term Objective:
The objectives, among others, include; managing the project, conducting a social mapping exercise to develop an information matrix with input by Africans, empowering beneficiaries to participate in initiatives to improve on their health, engage in community and social events to raise awareness on link between diet, play and mental-health. Disseminate information in form of newsprint pull outs, social media apps and use of other communication means. Set up African community event days where among other activities, proper nutrition is encouraged, health, hygiene, livelihood and socializing are promoted.
2.1.2  Short Term Objective:
2.1.2.1. To identify and generate a list of venues in San Francisco, Oakland, Brisbane, Richmond, Colma, Treasure Island, Daly City, South San Francisco and San Jose where drop-in meeting places where ‘diet, play and healthy living’ retreats or camps can be conducted.
2.1.2.2. To identify and work  with focal persons in San Francisco, Oakland, Brisbane, Richmond, Colma, Treasure Island, Daly City, South San Francisco and San Jose.
2.1.2.3. To identify and generate a list of health and human services facilities in San Francisco, Oakland, Brisbane, Richmond, Colma, Treasure Island, Daly City, South San Francisco and San Jose where drop-in meeting places where ‘diet, play and healthy living’ services are provided.  Make a list and develop a yellow page news print pull out.
2.1.2.5. To set up a management team for the full cycle of the project.
2.2     Problem Statement and Justification
Africans new in America are faced with challenges that in turn affect the way they access health care services and the way they engage in healthy living.  A paucity of tailored and funded programs catering to ‘diet, play and mental health’ among Africans has left them to access other integration and social services which are well funded but subsume the need for a stand-alone DPM program.  This is a gap that can be filled by dedicated communication for behavior change.
2.3     Proposed Interventions /Solutions (April 2015-March 2016)
2.3.0. To establish a resource and drop-in center as a static facility to conduct activities geared at entrenching good Diet, Play and Mental-health (DPM) practices, by April 2015.
2.3.1. The first proposed activity is setting up linkages through department of health, SF, Mayors’ offices and other service providers whose mission is geared towards health and development. Meanwhile a social media and hotline facility will soon be established by May 2015.
2.3.2. To identify and generate a list of venues in San Francisco, Oakland, Brisbane, Richmond, Colma, Treasure Island, Daly City, South San Francisco and San Jose where drop-in meeting places where ‘diet, play and healthy living’ retreats or camps can be conducted, by June –July 2015.
2.3.3. To identify and work  with focal persons in San Francisco, Oakland, Brisbane, Richmond, Colma, Treasure Island, Daly City, South San Francisco and San Jose, by May 2015.
2.3.4. To identify and generate a list of health and human services facilities in San Francisco, Oakland, Brisbane, Richmond, Colma, Treasure Island, Daly City, South San Francisco and San Jose where drop-in meeting places where ‘diet, play and healthy living’ services are provided.  Make a list and develop a yellow page news print pull out, by June 2015.
2.3.5. To set up a management team for the full cycle of the project, by May 2015.
2.3.6. To design, develop and maintain a website with updated tips and information on healthy living targeting Africans new in America, by May 2015.
2.3.7. To develop a schedule to promote and engage Africans in conscietization and owning of good Diet, Play and Mental-Health (DPM) related practices. This will use informal and formal meetings as means of guiding conversation and decisions to adopt healthy living lifestyles. Households will be encouraged to engage in such activities like ‘game nights.’ It will then be possible to start healthy living conversations or even continue with them.
2.3.8. Develop a yellow pages pull out with addresses and locations where Africans can meet, socialize and start or continue conversations around diet, play and healthy living.
2.3.9. Link up with service providers and solicit for space, time and tailored opportunities to increase African new Immigrants’ conscientious utilizing of services.
2.3.10. Develop the “drums-and-fire” networks to check on or support each other as part of adherence and decision support mechanisms. This will tap into contacts’ lists as well as a list-serve. This will also employ another mobilization tool among Africans called the “ear-to-the-ground.” This derives from ancient African ways of sharing information. Info-blasts will be maintained through the list-serve, elders of communities, religious leaders and social media platforms.
2.3.11. Involve Africans in extravaganza activities focusing on health with the support of Certified Therapeutic Recreation Specialists (CTRS), social workers and counselors.

3.0     Project Technical Approach / Activities
Project activities / objectives will mainly involve mobilizing Africans to access DPM related services.
3.1     The following are the aspirations:
(i). Designed and presented concept note.
(ii). Identified the leaders, role models and facilitators.
(iii). Developed the strategic line concept note to become the blue print for budgeting.
(iv). Demonstrated how one can establish a well-coordinated and integrated use of community or social events to integrate ‘Diet, Play, Mental-Health’ related services.
(v). Have rolled plans and schedules for interventions to be carried out over a period of implementation.
(vi). A yellow page pull out with information that is ‘Diet, Play, Mental-health’ related.
4.0     Monitoring and Evaluation
4.1. Monitoring will be continuous at various levels and will mainly be participatory in nature using attendance and exit reports to gauge impact. The yellow pages will regularly be distributed and updated; on spot visits at planned events will be an opportunity to collect data and consolidation activities.  Reported data will be collected and collated for processing. Media outlets will be involved in reporting outcomes.
4.2. A monitoring tool will be developed to report on uptake, popularity of program and any other experiences. It will be possible to increase on gender related participation in as a health seeking outcome.
4.3. This initiative will also be monitored by sponsors. Quarterly implementation and financial reports shall be sent regularly to sponsors.
4.4. Evaluation of impact will be undertaken based on the following indicators:
i. Number of events in different cities or localities
ii. Number of referrals and linkages.
 iii. Continuity.
5.0.    Sustainability
5.1. The initiative will focus on use of appropriate and locally available resources. The attendant capacity building of the beneficiary communities in participatory skills is hoped to have three outcomes: individual empowerment in linking diet, play on mental health; increased utilization of services; and managing time for self-improvement.



[1] Thomas Rogers M. M, is a resident of USA since 2012. He worked in Uganda with Ministry of Health as an officer under Communicable and Non-communicable disease Commission. He worked in 15 African countries under the Eastern and Southern Africa Health Network. In USA, he is a volunteer with UCSF, HIV/Hepatitis Community Advisory Board. He has interacted with many Africans in the Bay Area and this concept is the outcome of that interaction. You are reading it because Thomas is soliciting your support to start the BayHeal Initiative.
[2] Food, Music/Entertainment, Parenting, Grooming, Work and Housing are 6 aspects that draw Africans in Bay Area together. Knowledge of dates, activities & venues (DAV tool) will get one the numbers to reach out to with messages. Radio stations (e.g. KALW FM 91.7 has African night on Thursday-9am-11am).
[3] An organization engage in planning trade fares and market place-related activities all over California. In the Bay Area, it has featured at: Santa Rosa, San Jose, Ashley and San Francisco Market places.
[4] Health, nutrition, quality of life plans include: Safe motherhood, mental-health, Oral Health, diet plans, medical checkups, exercise and such activities promoting health.
[5] Eritreans (^ 400[ below 21; 100]), Ethiopians (^300[below 21; 100), Somali (^200[below 21;90]), Ugandans (^300[below 21; 100]), Kenyans(^700[below 21; 300]), Sierra-Leoneans(^100), Senegalese (^100), Liberians( ^100), Mozambiquans(^60) Angolans(^70) Ghanaians(^900[below 21; 400]), Nigerians(^1,000[ below 21; 400]), Zimbabweans(^100), Congolese(^100), Egyptians(^500), Moroccans(^200), Zambians(^60), Malawian(^40). These figures are arrived at from anecdotal responses. There could be more. It requires a bigger sample, perhaps more resources and a better structured inquiry will reveal better numbers.
[6] San Francisco, Oakland, Brisbane, Richmond, Concord, Colma, Treasure Island, Daly City, South San Francisco and San Jose have services ranging from Hospitals, Human Services’ Agencies, Department of Public Health and various support organizations.

[7] HBV-HIV Research Study (415-206-8236), Bridge HIV study part of the join prep.org. , shape up San Francisco part of the Opentruthnow.org. , ymacasf.org/bayview, SFrecpark.org, Project Open Hand Diabetes Study, Stop Smoking Classes by SFSmokegree.org at 2550 23rd St. Bldg. 40, 5th Floor, Solarium Classroom, SFGH (this may even demystify or assuage the hospital aversion), HIPS Study on Communication between Women and their doctors for 45-65 year olds; Study on Women’s Health, Aging &Sexuality. Information such as: appointment scheduling at say, Family Health Clinic (this may help improve on planning and attendance at clinics). Cal wellness with tailored prevention, primary care, health education/outcome plans and oral health.
[8] Plans can be made to enable beneficiaries benefit from utilization of these resources: Bayview, Hunters Point, Bernal Heights (in-door basketball Courts on 500 Moultrie St.), Balboa Park, Castro (the Eureka Valley Rec. Center on 100 Collingwood St.), Chinatown (Betty Ann Ong Chinese Recreation Center on 3rd floor, 1199 Mason St. or the Willie Woo Woo Wong Clubhouse on 830 Sacramento St.), Excelsior Park (McLaren Park, University St. at Mansell St.), Glen Park &West Portal ( Glen Canyon Park recreation Center, Bosworth &O’Shaughnessy Blvd.), Mission (Power play for 6-18, Boys & Girls Club of SF Tenderloin Clubhouse, 115 Jones St.). Western Addition (Hamilton Recreation Center 1900 Geary Blvd.)
[9] See 8 above.
[10] Anthropo-ethno tools.

Enjoy these articles, I did!

Zero HIV Transmissions in Mixed-Status Couples Having Condomless Sex

As reported today at the 21st Conference on Retroviruses and Opportunistic Infections, the multinational PARTNER study found zero HIV transmissions from condomless sex within mixed-HIV-status couples when the HIV-positive partner had his or her viral load suppressed below 200 copies/mL.
Alison Rodger
Alison Rodger at CROI 2014
Alison Rodger of University College London presented interim data from the study, which involved “serodifferent” couples who reported having condomless sex and not using PrEP or PEP (post-exposure prophylaxis), and in which the HIV-positive partner was on suppressive antiretroviral therapy (ART).
“I think we all acknowledge it’s critical to understand the absolute risk of sexual transmission of HIV through condomless sex for a person on ART with an undetectable viral load,” Rodger stated.
Every six months, PARTNER study participants completed a confidential sexual behavior questionnaire, and HIV-negative partners were tested for HIV infection. “Couple-years” of follow-up—that is, the number of years each couple was followed during the study—were included in this interim analysis only if the pair reported continued condomless sex without using PrEP or PEP, and if the HIV-positive partner’s latest viral load was below 200 copies/mL.
Although participants received counseling around condom use, only data from couples who reported having sex without condoms were included in the analysis.
In total, 767 couples contributed 894 eligible couple-years of follow-up (CYFU for short). New HIV infections were phylogenetically linked: Researchers analyzed samples of HIV from the newly infected partner and the HIV-positive partner to determine whether the transmission occurred within the couple or originated with an outside partner.
The analysis included 282 gay male couples and 445 heterosexual couples. The estimated number of penetrative sex acts (with or without ejaculation) was 16,416 in gay male couples, 13,728 in heterosexual couples with an HIV-positive male partner, and 14,295 in heterosexual couples with an HIV-positive female partner, for a grand total of approximately 44,439 sex acts. During the study, couples had condomless sex a median of 45 times per year.
Curious about the changing norms around condom use and HIV prevention? See “Raw Sex—Are the Rules Changing?” on BETA.
Jens Lundgren at CROI 2014
Jens Lundgren at CROI 2014
“In the absence of ART, we would expect to see a significant number of transmissions,” Rodger noted. “In fact, for HIV-negative MSM [men who have sex with men], based on the number and type of sex acts, we would have expected approximately 86 transmissions in the absence of ART.” The total number of sex acts across the two groups would have been expected to result in 50 to 100 HIV transmissions in the absence of ART, added Jens Lundgren of the University of Copenhagen in a press conference.
HIV transmissions did occur in follow-up—but only from outside partners, Rodger explained. None were phylogenetically linked to the original HIV-positive individual in any couple. “Overall, we had no linked transmissions during eligible follow-up, giving a transmission rate of zero.”
This important finding speaks to the added preventive benefit of effective HIV treatment, and fills a gap in the research literature regarding the efficacy of “treatment as prevention” in gay male couples.
Don’t miss stories like this—get BETA in your inbox! Subscribe.
However, the longer-term transmission risk linked with suppressive ART may not be zero, Rodger and Lundgren both emphasized. Although no within-couple transmissions occurred over the study period in this particular sample of mixed-HIV-status couples, the study team’s statistical analysis estimates that overall ten-year risk is 4% for any of the reported penetrative sex acts, close to 10% for anal sex, and 32% for receptive anal sex with ejaculation.
Zero transmission risk “is our best guess,” explained Rodger, but more data are needed—particularly for couples having anal sex with ejaculation—to strengthen estimates of transmission risk in the setting of viral suppression.
To this end, the PARTNER2 study aims to enroll and follow 450 gay male couples through 2017. The goal of this further study, Rodger explained, is “to provide more precise estimates for transmission risk, to inform policy, [and] also to inform individual choice on whether to use condoms or not.”
“It really is up to people themselves to judge if anything they do in life is ‘safe’ or ‘not safe,’” Lundgren stressed in the March 4 press conference. That said, these interim results have implications for legal issues around HIV, and for avoiding unnecessary use of post-exposure prophylaxis: If the HIV-positive partner has a fully suppressed viral load, Lundgren observed, “there is no reasonable legal action you could take against people who aren’t using condoms, and there’s really not a major concern if the condom breaks—and there’s certainly no indication for PEP.”
There’s more from CROI 2014—see BETA’s complete conference coverage.
Reilly O’Neal is a freelance writer and former editor of BETA.

Abstract

153LB: HIV Transmission Risk Through Condomless Sex If HIV+ Partner On Suppressive ART: PARTNER Study
Alison Rodger, Tina Bruun, Valentina Cambiano, Pietro Vernazza, Vicente Estrada, Jan Van Lunzen, Simon Collins, Anna Maria Geretti, Andrew Phillips, Jens Lundgren, for the PARTNER Study Group
Background: The absolute risk of sexual HIV transmission on stable ART (HIV RNA viral load (VL) <200 c/mL) from condomless sex is unknown. Current limited data are largely focusing on vaginal sex.
Methodology: The international, observational multi-centre PARTNER study prospectively follows serodifferent couples (heterosexual (HT) and MSM) who had condomless penetrative anal or vaginal sex in the month prior to study entry, and where the HIV+ve partner is on ART. Every 6 months, each partner completes a sexual behaviour questionnaire and the negative partner tests for HIV. Eligibility of follow-up time in this transmission rate analysis required: continued condomless sex; not using PEP or PrEP; and latest VL <200 c/mL. For new diagnoses, phylogenetic analysis compared HIV-1 pol and env sequences by couple, after samples were anonymised. This planned analysis reports the rate of occurrence of linked transmissions.
Results: By 1st November 2013, 1110 couples were enrolled. Of 1151 couple-years of follow-up (CYFU), 894 were eligible (586 in HT and 308 in MSM). At baseline, the median duration on ART was 4.9 years (IQR: 1.9-11.4) and couples reported having condomless sex for a median 2 years (IQR: 0.5-6.3). Condomless sex with a different partner outside the partnership during follow-up was reported by 27% MSM and 2% HT HIV-negative partners. During follow-up, couples had condomless sex a median of 45 times/ year (IQR: 16-90). Although some negative partners became HIV positive during FU, no phylogenetically linked transmissions occurred, giving a rate of within-couple HIV transmission during eligible couple-years of zero (95% CI: 0-0.40/100 CYFU)(Table). The upper limit of the 95% CI for the rate of transmission was 0.96/100 CYFU for condomless anal sex (HT and MSM) and 1.97/100 CYFU for condomless receptive anal sex with or without ejaculation (MSM).
Conclusions: The overall risk of HIV transmission (in the context of previous sex without transmission) through condomless anal or vaginal sex from HIV positive people on ART with plasma VL < 200 copies/mL is extremely low, but uncertainty over the risk remains, particularly over receptive anal sex. Additional follow-up in MSM is essential to provide more precise estimates for transmission risk given the current assumptions of safety in some communities.

Are you interested in HIV-progression, reservoir and latency? I enjoyed reading this article. Enjoy and learn!

Shock & Kill: Progress in HIV Cure Research

ViralReservoirA new class of latency activator, a TLR7 agonist—used to “shock and kill” HIV-infected cells—has shown promise when tested in animals and represents an exciting development in the HIV cure research field. A fully effective “shock and kill” method would ultimately help people with HIV reduce their viral reservoirs—and achieve a functional cure for HIV.
The “shock and kill” or “kick and kill” approach is the leading effort in HIV cure research at this point in time, said Steven Deeks, MD, a professor of medicine at the University of California, San Francisco (UCSF) and a faculty member in the Positive Health Program at San Francisco General Hospital, during a recent HIV cure presentation hosted by Project Inform.
Latently-infected CD4 cells, part of the so-called “viral reservoir,” have thus-far posed an insurmountable challenge to HIV cure strategies. These cells, while they aren’t actively producing new virus, do contain viral DNA and are able to “hide” from immune system cells that would normally target and destroy them. They’re the reason that HIV is able to rebound, from previously undetectable levels, if successful antiretroviral therapy is stopped.
New research presented by James Whitney, PhD from Beth Israel Deaconess Medical Center, Harvard Medical School at the Conference on Retroviruses and Opportunistic Infections (CROI) in February (abstract 108) showed that a TLR7 agonist—which stimulates immune cell receptors called TLR7—effectively reduces viral reservoirs using the “shock and kill” approach.
Whitney’s team infected Rhesus macaques with simian immunodeficiency virus (SIV), a virus similar to HIV that infects monkeys, and approximately 60 days post-infection, initiated antiretroviral therapy (ART) with tenofovir/emtricitabine/dolutegravir. All of the monkeys quickly suppressed their viral loads to under 50 copies per mL.
About 320 days post-infection, the researchers started giving four of the monkeys escalating doses of the TLR7 agonist. They found that TLR7 reliably produced viremic “blips” when administered at the highest dose (0.3 mg/kg), and that these blips were fairly robust—over 500 copies/mL in all four animals by the fifth dose.  No blips were observed in animals treated with placebo. This means that the agonist successfully “shocked,” or reactivated virus-infected cells from the viral reservoir, bringing them out of hiding from the immune system, to start producing new copies of HIV.
“This was extremely exciting data to us,” said Whitney.
The researchers also measured the agonist’s effect on the immune cells—CD8+ and NK T cells—whose role it is to “kill” SIV-infected cells. Doses of TLR7 led to increased activation of both CD8+ and NK T cells (i.e., greater numbers of these white blood cells were being produced). “There’s a fairly nice dose-response to CD8 activation levels, with a similar pattern of transient yet quite potent NK cell activation as well,” explained Whitney.
When antiretroviral therapy was stopped, viral rebound occurred in both the placebo-treated and TLR7 agonist-treated monkeys. But levels of SIV RNA rebounded to much lower levels in TLR7 agonist-treated monkeys. In other words, TLR7 agonist-treated monkeys controlled virus much better after they stopped treatment.
“There is a very clear reduction in plasma set-point values in the animals that received the TLR7 treatment,” said Whitney, a finding he described as “very interesting.”
Further investigation of peripheral blood mononuclear cells (PBMCs), lymph node, and colon samples found that SIV proviral DNA (a measure of latent or inactive HIV-infected cells) was much reduced in TLR7 agonist-treated monkeys. This finding provides fairly clear evidence that the drug worked well to activate, and reduce, the viral reservoir.
Further clinical research is needed to demonstrate that TLR7 agonists can effectively, and safely, reduce viral reservoirs in people with suppressed viral loads stable on ART. Gilead Sciences announced at the end of February that they will move forward with a TLR7 agonist Phase 2 clinical trial in humans based on the positive results from this study.