NIH Announces June 2017 “Concepts”

See the new Council-approved concepts at Concepts: Potential Opportunities for the National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) at: Concepts represent early planning stages for program announcements, requests for applications, or solicitations for Council’s input.

Support Groups a Driver to PrEP Rollout in Kenya

Contributed by Alfred Itunga, Technical Communications Officer at LVCT Health. This post first appeared on

Kenya passed a major milestone in the fight against HIV on May 4, 2017 when it launched a nation-wide initiative to bring oral PrEP (pre-exposure prophylaxis), antiretroviral drugs for preventing HIV, to the people who need it. The hope that oral PrEP will help defeat HIV comes after important clinical studies, which showed the safety of the drugs and their ability to prevent infection if taken correctly and consistently. But what works in the lab has to work in the real world too. A number of demonstration projects, aiming to answer the outstanding questions of how best to deliver oral PrEP, started offering PrEP before the launch of a national scale-up. The larger rollout will look to those projects to learn what worked well and what didn’t, and design a successful program. LVCT Health led a demonstration project called Introducing PrEP into HIV Combination, or IPCP, at multiples sites.

The three-year IPCP project focused on reaching populations at risk of being exposed to HIV in counties where HIV rates are high. Young women, female sex workers and men who have sex with men in Kisumu, Homa Bay and Nairobi counties of Kenya were enrolled in programs that offered daily oral PrEP. Program implementers answered their questions, counseled them through the effort to adhere to a daily regime, and collected evidence that would inform others about how to deliver PrEP as part of an HIV combination prevention package in Kenya.

A team made up of LVCT Health staff and AVAC staff recently visited the implementing sites to gather stories and collect lessons learnt as part of the OPTIONS project. We interviewed providers, adherence counselors and people using PrEP who shared their journeys of PrEP uptake and adherence.

People using PrEP pointed to support groups as one of the most important resources they depend on to help them maintain good adherence. The groups consist of 10-15 people who are self-led and meet regularly to share their experiences and challenges in using PrEP. I had an opportunity to attend a female sex worker support group in Kisumu and witnessed what happens during the meetings.

Monica, a PrEP peer leader, started the meeting by welcoming twelve others attending this support group. After each participant shared something about themselves, the group took up the subject of adherence while a note taker kept track of the discussion.

Lucy was among the first speakers. She has been able to keep up with a daily dose of PrEP, something many others struggle with. She said that she has been a female sex worker for 5 years and has been taking PrEP for the last year, catching the attention of those who have been using PrEP for a shorter period. Lucy continued to share her experience of using PrEP in the first two weeks which she confessed were the most challenging.

“I would feel nauseated, headaches and stomachaches, but after visiting the clinic and talking to the nurse, I was informed that these feelings would stop as soon as the body got used to the drugs and this surely did happen, after two weeks these side effects disappeared.”

Lucy said that during that time she almost gave up on PrEP taking, but what kept her going was the fact that she had lost her mother to HIV and could not imagine getting infected. She wants to remain healthy and HIV negative for her daughter. She also said that meeting with her peers during the support groups and hearing the same challenges she experienced made her grow stronger.

Her story generated some discussion as members loosened up and began to share their own experiences. “One time I forgot to take my pill since I was late from visiting a client. The following day I took two pills to compensate” one person said. This raised an argument as some thought it is not right while others said it was.

The service provider was at hand and advised that it is wrong to take two pills at a go and said that it’s too big of a dose. This reaffirmed those who felt it was wrong and users were advised that if for any reason they forgot to take their daily dose, they should continue with their dosage the following day.

I can see the support group meetings not only help people feel supported but also gives them an opportunity to get information and professional guidance on the challenges they face. Considering PrEP is a new prevention option in Kenya and the significant stigma associated with HIV in Kenya, the support groups give assurance to people and a platform to identify solutions to some of the challenges that they face.

It shouldn’t surprise anyone familiar with the HIV response that support groups have emerged as an important resource for a successful PrEP program. For years now, support groups have been pivotal for those on treatment, helping people living with HIV to adhere to the demanding regime of antiretroviral treatment. Providing a protected space for peers to discuss their challenges, such as managing medication or the stigma associated with HIV, is now a time-tested model.

At these LVCT demonstration sites, providers say the support groups have been invaluable. Maryanne, an LVCT Health PrEP service provider from Homa Bay, says at first only a few expressed an interest in the support groups. But those few kept coming and they kept telling others how much it helped. The support group got larger as young women confronted obstacles to adherence, which they wanted to overcome.

“One of the challenges that the users had was the rattling of the pills in the bottles, which made them feel uncomfortable while traveling with the drugs. This affected adherence. They would not carry the drugs when they travelled,” shared Maryanne.

Together they devised a way to keep the pills discrete. Maryanne began supplying cotton to stuff in the pill bottle. No more rattling. No more leaving the pills behind.

Whether it’s managing side effects, stigma or adherence, these group discussions offer personal, consistent support—something the IPCP programs developed in a number of ways. In the coming weeks and months, OPTIONS will be sharing a series of lessons learned from our visits to the LVCT demonstration projects. As a whole, these lessons will touch on a range of issues, but several will underscore what these support groups show. The challenges to good PrEP adherence are both individual and societal, both practical and complex. Enduring solutions often involved ready access to a trusted person who can offer guidance when the going is hard until the way gets clear again.

HIV Testing: A portal for treatment and prevention

Mitchell Warren is the Executive Director of AVAC. This post first appeared on

For years, HIV testing has been the cornerstone of plans to end the HIV/AIDS epidemic. Widespread testing programs have helped connect millions of people to HIV treatment and care and have been the first step in saving lives. However, an estimated 14 million more people who are living with HIV still haven’t been tested and remain unaware of their status and unconnected to the treatment and care they need, according to the World Health Organization.

As those of us in the US gear up to celebrate National HIV Testing Day — a day intended to remind us all of the importance of knowing our HIV status — it’s important to look at ways to leverage HIV testing, whatever the result, to link more people to the services they need.

The benefits of immediately linking people who test HIV positive to care and treatment are clear. With evidence and guidelines pointing to the benefits of “test and start,” should an individual want it, more people are being linked directly to antiretroviral treatment (ART) programs — ideally, the same day they get test results. This has a positive impact on the health of the individual being treated and an added effect of preventing onward transmission once an individual on treatment achieves viral suppression, a concept also known as Undetectable = Untransmittable, or U=U.

But what about those who test negative? HIV testing is not, in and of itself, a prevention service. However, HIV testing linked to comprehensive prevention services is — or at least it should be.

Comprehensive prevention is not just condoms, referrals for sexually transmitted infection (STI) treatment and — depending on where an individual lives in the world — possible counseling about voluntary medical male circumcision (VMMC) or pre-exposure prophylaxis (PrEP). It includes male and female condoms, condom-compatible lubricant, daily oral PrEP, STI treatment and linkages to the most appropriate and needed services, including VMMC, ART for partners living with HIV, opportunities to build social capital, financial support, harm reduction and much more.

In fact, if programs could leverage HIV testing expansion as an entry point for effective prevention, HIV prevention could be transformed and many of those most at risk of HIV could be reached with effective prevention options to protect themselves.

The key to this is regular and ongoing HIV testing for those most at risk. Many people in the US will hopefully heed the call for HIV testing on June 27th and take advantage of programs that make it easy to test on that day. But, will they be linked to effective prevention that is also right for them? Will they commit to ongoing testing as part of that prevention package?

The era of PrEP is also the era of regular HIV testing, since safe and effective PrEP use requires HIV testing on a regular basis to ensure that the mono- or dual-therapy is not being used by someone who has acquired HIV. As PrEP use is increasingly seen as an important and empowering act of self-protection for anyone who uses it, how can that same empowerment principle be extended to regular HIV testing for all who are at risk, regardless of the prevention options they access?

HIV testing programs have come a long way in the last three decades in cutting down stigma, making testing more accessible and linking people who test positive to care and treatment. But programs, policies and funding have not moved where they need to be to link HIV-negative individuals to the prevention options they need. Everyone who tests for HIV — no matter the result — needs to be linked to comprehensive, integrated and sustained services that are culturally appropriate.

Is this happening? How often is it happening? No one knows. Data on services offered to people who test HIV negative are inadequate. Outside of the US, countries, funders and implementers report on “people reached” by simply counting referrals and condoms distributed, yet data on who is being reached — particularly among populations at greatest risk — are insufficient. In the US, these linkages vary widely based on the availability of funding and other support to often overstretched clinics and local AIDS service organizations that run testing programs.

What is the solution to linking HIV-negative people to effective prevention services? Data show that connecting people to services immediately after testing can help keep them negative. There are global guidelines in place from the World Health Organization, and national guidelines exist in several countries, including from the Centers for Disease Control and Prevention for the U.S. But experience shows that guidelines and policies do not always reflect the reality of programs and, most importantly, people’s lives.

Moreover, funding plays a critical role in the realities of programs. Even as test-and-start treatment has become the standard that testing programs aim for in the U.S. and around the world, budget cuts and health care “reform” threaten to derail these evidence-based and policy-supported programs. Linking HIV-negative people to the services and care they need is likely to suffer even more with health care changes in the U.S. and domestic and global HIV budget cuts.

As advocates for evidence-based prevention, we at AVAC fight for policies that link all people who test to relevant, appropriate and user-friendly services. It’s the right thing to do for individual health and to end the epidemic — and it’s cost effective and cost saving.

So, on this National HIV Testing Day, we call on individuals to get tested, know their status and take appropriate steps to access treatment and prevention. And, we call on funders and policymakers in the US and around the world to support life-saving and cost-saving testing programs that are the cornerstone of a comprehensive, integrated and sustained response to HIV.

Now I Am Not Scared of Testing for HIV

This blog post, written by Thabo Molelekwa, first appeared on What’sUpHIV as part of a series covering the 8th South African AIDS Conference.

When Samkelisiwe Chiliza from Durban heard about Pre-Exposure Prophylaxis or PrEP, she did not hesitate to join the PrEP study through the Centre for Aids Programme and Research in South Africa (Caprisa).

PrEP is the use of anti-HIV medication to keep HIV negative people from becoming infected. PrEP has been shown to be safe and effective in clinical trials that have taken place in many countries, including South Africa, and is approved by the South African Medicines Control Council (MCC). Taken as a single pill once daily, it is highly effective against HIV when taken every day. The medication interferes with HIV’s ability to copy itself in one’s body after one has been exposed. This prevents HIV from establishing an infection and making one sick.

Samkelisiwe is one of the young women who are currently on PrEP in South Africa and she is encouraging other young women to participate in one of the PrEP projects taking place around the country so that they can help stop the spread of HIV and keep themselves safe.

“I have been taking one pill every night for the past 14 months and I am not willing to stop as I am saving my life,” said Samkelisiwe, adding that she is not scared of testing for HIV because she knows what results to expect since she is on PrEP.

According to Samkelisiwe, many young women are already infected and are not eligible for PrEP as it is only for HIV-negative people.

“Lots of people don’t know about these kind of studies but I do spread the word as much as I can,” she said.

She said that her grandmother was happy to hear that she is taking a pill to protect herself from contracting HIV.

According to Professor Linda-Gail Bekker of the Desmond Tutu HIV Centre, PrEP is a prevention option, not a treatment. It works properly when taken correctly and consistently, but that, currently, only 13,000 people who are receiving PrEP from the government. These are sex workers and men who have sex with men. And there are only 1,387 people who are taking PrEP through demonstration projects run by various organisations.

Prof Bekker said that, while PrEP is not yet widely available, “there is advocacy going on to make sure that the government rolls out PrEP to everyone who needs it.”

The high cost of PrEP is what stops the government from rolling it out to everyone who needs it. Currently, there are only two ways to access PrEP – “People can buy it at a chemist or they can join the demonstration projects that are taking place in the country,” added Bekker.

Bekker said that educating people in the communities about PrEP is important because that will give them knowledge of what the intervention is so that they can make decisions about protecting themselves from HIV and preventing the spread of the disease.

According to World Health Organisation guidelines, PrEP is rolled out to people at substantial risk of contracting HIV. Deborah Baron of Wits Reproductive Health and HIV Institute (WRHI), believes that in South Africa, PrEP should also be rolled out to young women because 7,000 young women become newly infected with HIV every week in Eastern and Southern Africa. “And a third of those women are right here in South Africa,” said Baron.

Baron said that in order to make PrEP interesting for young women there is a need for youth-friendly PrEP delivery models and tools. “We need to be responsive to realities of young women’s lives.”

In late 2015, the South African Department of Health developed policy and guidelines for oral PrEP as well as test-and-treat implementation to protect groups at high risk in line with World Health Organisation guidance. The ARV drug, TDF/FTC, was approved for use as PrEP by the Medicines Control Council.

The National Department of Health, together with the implementing partners, like Baron’s organization, continue to work together to move PrEP forward and get it to the people who most need it. Individuals like Chiliza who take PrEP and talk about it their peers are helping to expand an important HIV prevention option for South Africans.

Fareed Abdullah on ‘missed opportunities’ in the National Strategic Plan

This blog first appeared on What’sUpHIV as part of a series covering the 8th South African AIDS Conference.

There are many “missed opportunities” in the National Strategic Plan (NSP) for HIV and TB, said Fareed Abdullah, the head of AIDS and TB research at the Medical Research Council and former SANAC CEO, at the closing of the South African AIDS Conference.

The NSP has been criticized by a number of civil society groups and this has culminated in two demonstrations being held during the conference – one by a general group of activists and another by sex worker activists.

At a press briefing on the closing day of the conference, the South African National AIDS Council (SANAC) defended the NSP, saying that while it was “imperfect”, it had incorporated viewpoints from many sectors of society. SANAC largely blamed the critique of the plan on individuals and organizations who were unhappy with their loss of leadership in SANAC and the transformation that was taking place within its structures. They also rejected claims of corruption within the council.

“We now know that we cannot treat our way out of this epidemic,” said Abdullah. Rather, prevention interventions would be the answer, where the social and structural drivers around HIV were focussed on.

He said that a lot of work would need to be done to find the “sweet spot” of how much money should be invested in specific interventions such as the contribution of gender-based violence to HIV transmission, the role of alcohol as well as social factors such as hunger.

While the NSP provides a “good broad framework”, there are areas that are lacking, believes Abdullah. However, he said that there is still the possibility of improving the NSP.

One of Abdullah’s concerns is that the “toolbox” provided in the NSP “doesn’t match the impact that we’re looking for”. The NSP aims for a 37% reduction in new HIV infections by 2022.

He said that there is the need for a prevention agency that has substantial resources, a large reach and is able to implement multiple programs at community level.

“But at the moment we don’t really have an agency with the wherewithal, the authority and the institutional capacity [to do this].”

While there were “many steps forward on TB”, Abdullah said that “TB is nothing short of a national crisis”. A crisis that he believes needs to be addressed through leadership, management, logistics and an investment in drugs.

“It needs nothing short of a revolution in a short space of time,” said Abdullah.

As for the NSP’s much-talked about failure to include a recommendation for the decriminalization of sex work, Abdullah said that this was another “missed opportunity”.

Low targets were set for pre-exposure prophylaxis (PrEP), something that could be rapidly scaled up for key population groups such as sex workers, men who have sex with men and transwomen, said Abdullah.

“For 20 years [we] have always said that key populations are not essential but I think [we have] been proven to be fundamentally incorrect about that.”

He also warned about drug use becoming a major contributor to HIV transmission in the next five years.

Our Vaginas Are Our Own Affair

This blog post, written by Thabo Molelekwa, first appeared on What’sUpHIV as part of a series covering the 8th South African AIDS Conference.

Dr. Tlaleng Mofokeng, 33, has harsh words for those who want to own women’s vaginas. “Everyone has an opinion about the vagina,” she said. Young women in particular, she said, are constantly judged.

“They are told to keep their legs closed; stay in school: use birth control and say no to blessers. Yet when we ask for services such as contraceptives and abortions, we are criticized.”

Dr. Tlaleng is the chairperson of the track examining social, political, economic and Health Systems at the 8th SA AIDS Conference in Durban. It was about a decade ago in medical school when Free State-born Tlaleng Mofokeng realized that her interest lay in sexual health care, reproductive health care and ethics and rights. She now a runs medical practice in sexual health at DISA clinic in Sandton, Gauteng.

She is also widely known for her Sunday Times column on reproductive health and her no-nonsense radio slot on the same subject on Khaya FM.

Every week, around 2,000 young women are infected with HIV. But most of the HIV prevention campaigns are male-centred. Female condoms are not really available, for example, says Dr. Tlaleng. “When having sex, we must wait for the man to put on a condom. Yet we are the ones who are a higher risk of getting infections.”

Dr. Tlaleng believes that the policies on HIV and STIs in schools are not implemented correctly. “They talk mainly about abstinence instead of talking about other prevention methods. There are young people right now who are HIV (positive) in school and no one is talking to them.”

Dr. Tlaleng is also concerned that young people born with HIV have very little information about how to disclose their HIV status to their partner.

“During my last year in medical school I launched the first youth friendly clinic as a ground breaker in Matatiele.” Said Dr. Tlaleng “And with support from my University we did a very good job to ensure that the young people there were connected to other people in terms of institutional support.”

Circumcising Babies ‘Would Be Acceptable’

This blog post, written by Zizo Zikali, first appeared on What’sUpHIV as part of a series covering the 8th South African AIDS Conference.

The department of health in partnership with USAID and The Centre for HIV and AIDS Prevention Studies (CHAPS) are working together to fight the HIV/AIDS epidemic by developing a safe and sustainable service delivery model for early infant male circumcision in South Africa.

Chief executive officer of CHAPS Dirk Taljaard said CHAPS conducted a study examining the feasibility of early infant male circumcision in Soweto and Orange farm in Johannesburg, Gauteng. Nearly 70 percent of 304 urban mothers and 142 fathers showed interest of circumcising their sons before they were six weeks old.

“The study concluded that early infant male circumcision would be acceptable in the country; despite the pull of traditional circumcision during adolescence among certain ethnic groups. However, there should still be discussions at national, provincial, district and local level as soon as possible.”

There was some dissent. Siyabonga Zulu, a 34-year-old man from Umlazi, south of Durban, believes that circumcising a minor would be violating their rights. He believed a child should be circumcised only when he has reached an age when he could decide for himself whether to opt for medical or traditional circumcision.

HIV Prevention at This Week’s South African AIDS Conference

The South African AIDS Conference (SA AIDS) kicks off Tuesday at the International Convention Centre in Durban. SA AIDS is an energizing, biennial conference that brings together a cross-section of the people and organizations sustaining the HIV/AIDS movement in South Africa.

This year’s theme, The Long Walk to Prevention: Every Voice Counts, comes at a critical time for HIV research and rollout in South Africa. In a time of both great uncertainty, but also of exciting dynamism in the prevention field, AVAC is thrilled to see the conference focusing on this essential component of a comprehensive AIDS response.

Whether or not you’ll be Durban, you can engage with AVAC and partners at SA AIDS in a variety of ways. We have gathered a full roadmap of prevention research-oriented events and presentations. Download our roadmap here, and the full conference program here.

Below, we’ve highlighted some key sessions.

  • Community Village — An interactive and participatory space to discuss cutting-edge issues in HIV, share knowledge and skills and network. Open to conference participants and to the general public.
  • Research Literacy Networking Zone — Wits RHI in partnership with AVAC, SAHTAC and APHA will disseminate research literacy materials and conduct fun and educational games focused on HIV prevention research R&D and advocacy. The zone will be located in the Women’s Networking Zone within the Community Village.
  • HIV Prevention and SRHR Masterclass
    Tuesday, June 13 – Thursday, June 15, 7:00 – 8:30 — Hosted by the African Alliance for HIV prevention at the Hilton Hotel.
  • Satellite Session: PrEP (sponsored by Gilead)
    Tuesday, June 13, 11:30 – 13:00 — Located in Hall 8b.
  • Up Your Game: Play to Learn About HIV Prevention and Research
    Tuesday, June 13, 12:00 – 13:00 — An HIV prevention research literacy game hosted on the main stage in the Community Village by AVAC, WRHI, SAHTAC and APHA.
  • Dapivirine Ring Licensure Program
    Tuesday, 13 June, 18:00 – 20:00 — This interactive satellite session, hosted by IPM, will showcase the developments in the dapivirine vaginal ring program. Located in Hall 5.
  • Basic Science: Putting the spanner in the works – the nuts and bolts of HIV prevention
    Wednesday, June 14, 9:00 – 11:00 — A roundtable plenary discussion with leading scientists. Located in Hall 1.
  • Improving HIV prevention by investing in research and development and services
    Wednesday, June 14, 11:30 – 13:00 — This workshop will provide health advocates and technical experts from the HIV prevention sector a platform to share ideas on how to improve implementation of R&D policies, and streamline regulatory processes that support the development, introduction and scale of high-impact health technologies in South Africa. Located in Hall 10.
  • Contraception and HIV: What they say, what we hear, what needs to change — a young women’s dialogue
    Wednesday, June 14, 18:00 – 20:00 — A roundtable dialogue with young advocates. Located in the Women’s Networking Zone.

You can also meet the AVAC team, learn about the Advocacy Fellows Program and pick up copies of our materials at the Research Literacy Zone, located in the Women’s Networking Zone in the Community Village.

As always, AVAC will be posting live updates from the conference on its Twitter and Facebook pages. Follow all the conference proceedings via its hashtag #SAAIDS2017. And look for updates from a cadre of young community journalists whose conference updates will be posted on the WhatsUpHIV blog.

We look forward to seeing many of you in Durban. Please stop by to say hello!

Long-Acting Injectable Antiretrovirals for PrEP: Will the tail wag the drug?

Mark Mascolini is a medical journalist who writes about HIV news, research and global policies for the International AIDS Society and many publications. Emily Bass is the Director of Strategy & Content at AVAC.

A medicine you get only every two months to reduce your risk of acquiring HIV sounds like a great deal. And that could be an option in the future. But only if two big efficacy trials of long-acting injectable cabotegravir (CAB-LA) show that it is safe and effective. The strategy in question is one shot of this long-acting antiretroviral (ARV) in the buttocks every 8 weeks. The questions the two trials are asking are whether this type of PrEP is safe and well tolerated and whether it will help shield trial participants—women, men who have sex with men (MSM), and transgender women (TGW)—from HIV.

We already know that long-acting CAB, an investigational HIV integrase inhibitor, prevents rectal, vaginal, and intravenous infection with simian HIV (SHIV) in monkeys. Studies in animals aren’t a guarantee of results in humans, but these and other data have helped move the candidate into human studies. A Phase 2 trial of CAB-LA for prevention (ECLAIR) was recently completed among men; the HPNT 077 Phase 2 trial among women and men is due to present results soon; and the drug is now moving into two efficacy trials (HPTN 083 and HPTN 084).

A combination of CAB-LA and another investigational injectable, the nonnucleoside antiretroviral rilpivirine (RPV), is being studied for treatment in people living with HIV and showing good results. In the treatment context, injectable ARVs are given to people who have undetectable viral loads using standard, pill-based regimens. So far it looks like long-acting injected CAB plus RPV every 4–8 weeks safely maintains HIV suppression. The combination has entered Phase 3 trials in people living with HIV who have been on antiretroviral therapy before, and those who have not. (RPV was also studied for long-acting PrEP in the HPTN 076 trial but is not moving forward into efficacy trials at this point.)

Despite this early run through the research gauntlet, pressing questions remain about the safety and routine use of long-acting injected antiretrovirals. Initial questions about acceptability can be partially explored now in the trials, but for injectable PrEP, as for any new strategy, there would need to be a robust agenda of follow-up investigation, should the efficacy trials show positive results. Some of the questions include:

  • Will there be adherence advantages of shots given every two months over daily pills in practice—and/or will intermittent injections raise other problems?
  • Will the good early side-effect scores of CAB-LA hold true outside clinical trials—or will the almost-routine injection reactions turn off possible bi-monthly-shot recipients?
  • Will the striking staying power of CAB-LA and RPV in a person’s body—the long duration that makes infrequent shots possible—lead to side effects whose risks outweigh the benefits and convenience of the tool?
  • In people with HIV who use long-acting CAB-LA and RPV, will HIV spawn resistant mutants during the months-long low-level drug “tail” that lingers when a long-acting dose is not followed by another?
  • In people who are HIV-negative and using CAB-LA for PrEP, what’s the strategy for dealing with the tail when coming off PrEP? Oral PrEP is one option but could be unpopular with people who opt for the injection. Yet exposure to HIV during the period when the drug is still in the body could lead to drug resistance, if infection occurs. In other words, will the tail wag the drug?

This report considers the evidence so far, with a focus on long-acting injectable CAB for pre-exposure prophylaxis (PrEP) to prevent HIV infection. Here’s what we know and don’t know right now.

We know an injection won’t be perfect for everyone.

Easier adherence remains the premier promise of long-acting antiretroviral PrEP or treatment. For lots of people, getting a shot in the butt every two months sounds much simpler than popping a Truvada (TDF/FTC) tablet every single day—or remembering to dose up before and after sex. But experience from many arenas—particularly contraceptives—tells us it won’t be the simpler choice for everyone. Countless people have no trouble remembering to swallow a multivitamin every day; they might more easily lose track of an every-eight-weeks multivitamin shot. Some women like a daily birth control pill; others prefer a long-acting method such as an implant or an injection. There will almost certainly be people who can take a daily PrEP pill with calendrical consistency but find the eight weeks between PrEP shots a slick slope to dosing amnesia.

The trials can’t predict preferences or the chances that people will fall into this two-month memory trap. Clinical trials of injectable PrEP or treatment require people to come to a clinic for their injections. We do know that women taking hormonal contraceptives can struggle with consistency and that research in the US and in sub-Saharan Africa has found that many women can forget to return for their scheduled contraceptive injection.

Trials of CAB-LA for PrEP start with four or five weeks of daily oral dosing to make sure people can tolerate the drug. But PrEP experts observe that these preliminary weeks of daily pill taking may prove challenging to people trying injected PrEP precisely because they struggle with once-a-day dosing.

We know frequent (or rare) side effects may pose safety concerns.

Safety data on long-acting CAB and RPV are accumulating from the trials to date. Through 32 weeks in the 286-person LATTE-2 trial of injected CAB/RPV for treatment, two people out of 115 (2 percent) getting their two-drug shots every eight weeks dropped out because of possible side effects (both injection-site problems), while six people out of 115 (5 percent) getting shots every four weeks stopped for possible side effects.

People living with HIV may be willing to put up with more antiretroviral side effects than people taking antiretroviral PrEP to avoid HIV infection. In the biggest CAB-LA for PrEP trial reported so far, ÉCLAIR, 106 men were assigned to the CAB group; of these, 94 completed the oral dosing phase and entered the injection phase. After four weeks of oral CAB, these men got CAB-LA every 12 weeks. Four of 94 men (4 percent) who started the shots quit the study because they couldn’t tolerate the injections. Overall, 75 men (80 percent) who started CAB shots had moderate to severe adverse events. Injection-site pain, itching or swelling accounted for the lion’s share of these problems, compared with ten men (48 percent) who received the placebo injection. ÉCLAIR concluded that the injection schedule of 800 mg of CAB-LA administered every 12 weeks was suboptimal when it came to maintaining the drug levels required for protection against HIV; the eight-weekly regimen is proposed as a solution. (Results from the HPTN 077 trial of CAB-LA among approximately 200 HIV-uninfected men and women in 8 cities in Brazil, Malawi, South Africa and the US are anticipated later this year.)

A 2016 paper that looked at all of the data from trials of CAB-LA for treatment or PrEP to date found that roughly three-quarters of participants had injection-site reactions, usually mild or moderate. Nodules popping up at injection sites can be stubborn. The same paper reported that about half of injection site nodules lasted 22 days, about one-third of an eight-week dosing interval. Outside the hand-holding discipline of clinical trials, people already squeamish about needles who nonetheless agree to a big shot in the behind every eight weeks may fast run out of patience if they find the shots painful.

Injection woes may be the most frequent problem with long-acting shots, but they may not be the most serious. The remarkable durability of injected drugs like CAB and RPV—the very trait that makes infrequent dosing possible—also poses their greatest risk. Once you stop taking antiretroviral pills, the drug is gone in a few days, and you can shut off drug exposure by removing an inserted drug delivery system like the dapivirine ring or an under-the-skin TAF implant. But once an injected drug starts soaking target cells, there’s no way to get rid of it. And that could mean there’s no way to get rid of an out-of-the-blue side effect. Taking CAB or RPV pills for several weeks could uncover side effects that warn prescribers away from injecting the drugs in a few people. But that strategy may miss a surprise reaction that comes only after a hefty loading dose gets plunged through a one-way needle. Such reactions will probably be rare but no less troubling to individuals affected.

We know the “tail” is something to track.

After a single dose of CAB-LA or RPV, the slow fade of drug from the body means drug levels eventually fall beneath a concentration that shuts down HIV—unless a person gets another shot in the prescribed time. In the ÉCLAIR trial, CAB-LA remained detectable in blood in 14 participants (17 percent) 52 weeks after the last injection. If someone taking CAB for PrEP forgets a shot long enough—or just stops—and keeps having sex, low CAB levels could permit HIV infection. And when HIV starts copying itself in the face of meager antiretroviral levels, it starts making resistant copies.

This is not a theoretical scenario. It already happened to a woman who got a single 300-mg intramuscular shot of RPV. She tested positive for HIV 84 days after the shot, and after 115 days the infecting virus carried a mutation that confers resistance to the whole nonnucleoside class. The researchers call this “a unique instance of infection with wild-type [nonmutant] HIV-1 and subsequent selection of resistant virus by persistent exposure to long-acting PrEP.” To avoid repeating this misadventure, a person taking a long-acting injectable would have to have a clear HIV prevention plan for several months after the last shot—some combination of complete condom use, behavior change or covering the slowly waning tail of the injectable with faithfully taken oral PrEP, like Truvada.

We know the trial designs are complex.

December 2016 saw the launch of HPTN 083, a 4500-person double-dummy, double-blind trial of injectable CAB-LA PrEP every eight weeks. The trial is enrolling MSM and TGW in countries in North and South America, Asia, as well as in South Africa. Researchers estimate it could take 3.5 years to complete HPTN 083 but note that the trial is “endpoint driven,” meaning that the timing depends on the frequency with which new HIV diagnoses occur in participants. HPTN 084, a parallel CAB-LA PrEP trial in women, is also a double-dummy, double-blind trial and is expected to start later this year.

Does “double-dummy double-blind” sound familiar? It might not. This and other terms are relatively new in the biomedical HIV prevention field. But times have changed. The advent of daily oral PrEP as a WHO-recommended prevention strategy has propelled changes in trials of other prevention strategies—including ARV-based and non-ARV based prevention alike. (AVAC has developed a plain language glossary of some of the commonly used terms HIV Prevention Trial Terms: An advocate’s guide.)

The designs for HPTN 083 and 084 are examples of what efficacy trials look like in the “post-placebo” era. In a placebo-controlled trial, people are randomly assigned to receive either an active agent (like oral PrEP pills) or an identical “dummy” candidate (a sugar pill or a saline injection). Both groups receive the same HIV prevention package. HIV prevention trials involving people whose primary risk is sexual exposure all provide condoms, diagnosis and treatment of sexually transmitted infections and behavior change; some also now provide referrals for voluntary medical male circumcision, PrEP and partner testing and treatment.

For now, PrEP is not part of the standard prevention package in all HIV prevention trials (e.g., vaccine studies and more). It’s being provided on referral in countries where PrEP is also part of the national policy. But this approach won’t work for trials of long-acting injectable PrEP. Trial ethics require that a trial of a new method (an injectable PrEP) be compared to existing effective methods in the same category (daily oral PrEP).

For an in-depth look at HPTN 084 trial and the “lexicon” associated with such studies, check out AVAC’s most recent issue of Px Wire.

To meet this ethical imperative and get a clear, usable answer, the trials have to ask a new kind of question: how does injectable PrEP compare to daily oral PrEP when it comes to reducing the risk of acquiring HIV?

Because of the way that statistics work, this question has to be phrased very precisely. Broadly speaking there are two questions PrEP trials can ask in the post-placebo era:

  • Is this new experimental product better than a placebo or an existing product, e.g., is injectable CAB-LA better than daily TDF/FTC? A superiority trial asks this kind of question.
  • Is this new experimental product equivalent to or not worse than the existing product, by a pre-specified margin? A non-inferiority trial asks this kind of question.

These weighty questions about injectable antiretroviral adherence, safety, and resistance will probably take a few years to answer because big efficacy trials have just started signing up recruits.

We know that clinical trial success is only one step—and doesn’t always translate to impact.

If injectable PrEP or treatment works in trials, there will still be lots to explore about delivery in the real world.

Most people with HIV see their provider every 4–6 months; most HIV-negative individuals who may be candidates for PrEP see their clinician much less often, if at all. That will have to change if providers intend to give people antiretroviral injections for treatment or prevention every two months. There will be many other questions too about who is willing to pay for long-acting ARVs, what types of programs these tools would belong in—and more.

As we’ve learned from many strategies—from HPV vaccine to oral PrEP—if you wait until there is evidence of efficacy to begin addressing these questions, then you’ve waited too long. AVAC is working with CHAI as part of the Gates Foundation-funded HIV Prevention Market Manager project to frame and address key questions about long-acting PrEP. At the same time, we are working with many of our partners in civil society to ensure that the trial designs are ethical, the goals well understood, and the outcomes on track to achieve the ultimate goal—a sustained end to epidemic levels of new HIV infections worldwide.

See the AVAC infographic on long-acting injectables for a nuts-and-bolts review of testing these agents for HIV treatment and prevention; see: HIV Prevention Trial Terms: An advocate’s guide for definitions of many of the terms used in this article.

PrEP Stymied in Europe: What’s the hold up?

Cindra is a Senior Program Manager at AVAC.

Europe is the birthplace of the smallpox vaccine and the Renaissance, among other treasures. So why can’t this continent that has brought forth such cornerstones of public health and flourishing civilization deliver oral PrEP—a mere pill a day to prevent HIV, which already exists and is being successfully implemented in several countries, including Brazil, Kenya, South Africa and the US.

To be fair, France has been rolling out daily oral PrEP (consisting of Truvada) for over a year and a handful of others—Norway, Scotland, Belgium and Portugal—recently committed to provision plans. But the majority of countries on the continent are still struggling to even start to take PrEP to scale—even though there has been a 60 percent spike in HIV incidence in the past decade.

The delay isn’t due to lack of demand or a framework for PrEP provision. The call for PrEP from civil society is loud and clear, evidenced by the do-it-yourself droves ordering PrEP over the internet, clinic hopping, pill sharing and/or smuggling PrEP drugs into countries where it’s not available via the health system.

It’s been more than a year since the European AIDS Clinical Society Guidelines recommended PrEP and Europe’s regulatory authority (EMA) approved Truvada (emtricitabine and tenofovir) for PrEP. In England, the National Health Service argued that it didn’t have the mandate to introduce PrEP programs, as HIV prevention was the responsibility of district health authorities. The English High Court ruled otherwise and clarified that NHS did indeed have the power to launch PrEP programs. Even policy makers are warming to the idea of PrEP as more data from countries where PrEP is becoming available come in, suggesting that PrEP is working as HIV prevention in real-world settings.

So what’s the hold up? Many are pointing to the drug company Gilead, the patent holder of Truvada, the only PrEP drug licensed in Europe. Recently, Gilead obtained an extension of its Truvada patent in England, where the original copyright expires this year. The pharma giant is likely to keep prices high while facing no competition from generic manufacturers until 2021. That’s almost four years in a country with 17 seroconversions a day.

As a response to Gilead’s motion to postpone its patent expiry in England, several generic producers filed a lawsuit that was kicked up to the Court of Justice of the European Union. Now any legal decision will apply to all EU member states, not only England. “If the court finds in favour of the generic companies, the cost of PrEP could be accommodated within current budgets through the savings made in treatment costs,” wrote UK clinician advocates Sheena McCormack and Marta Boffito in The Lancet.

In the meantime, some health systems have hit the pause button on piloting PrEP. England is one example where its PrEP implementation has been delayed largely due to the prohibitive costs of the branded Truvada drug. Gilead has refused to waive its patent even for pending implementation studies. A planned 10,000-participant trial was slated to have started early in the year, but recruitment is now unlikely to begin until July.

Similarly, in Italy, the Bologna Checkpoint—a community-run rapid HIV and STI testing center—was poised to begin its PrEP implementation project, but the launch was thwarted when Gilead declined to provide donated or even discounted Truvada. They were told the company would no longer support PrEP implementation pilots in Western countries. The Italians then approached Mylan, the makers of a generic form of Truvada licensed for treatment in Europe. At first the generic supplier—a plaintiff in the case against Gilead—was happy to do business with Checkpoint but then opted to wait until the lawsuit was settled in the hopes of acquiring full marketing authorization to supply the discounted drug. As of yet there is no scheduled court date for the generic companies v. Gilead.

Activist Giulio Corbelli, of the European AIDS Treatment Group, doesn’t think Gilead is cynically strategizing to block PrEP access in Europe. Rather, he says, the company simply pursues its commercial interests, creating barriers to access in the process. “They are not negotiating with the competent national authorities to identify a route for selling the drug; they are not supporting any implementation projects with their drug; and they are doing whatever they can to prevent other companies’ support of such projects,” he points out.

In addition to protecting its Truvada PrEP monopoly in Europe, Gilead has another bottom-line business incentive to slow European scale-up efforts. The company has released a low-dose version of Truvada, known as F/TAF, for treatment. Gilead has just completed recruitment for a large-scale PrEP study that will compare its new drug F/TAF with Truvada, with results due in 2020. If F/TAF proves to be as effective as Truvada in reducing HIV risk, Gilead can bring this new formulation of the drug to the European market—right in time to replace an extended expiration of the Truvada patent in 2021.

The PrEP in Europe Initiative (PEI) sent Gilead an open letter asking the company to surrender its Truvada Supplementary Protection Certificate (patent extension). However, it’s not likely the company will cave based on its previous intransigence around its shamefully priced hepatitis C drugs. Short of a Gilead walk-back, activists are encouraging health ministries to advocate for an expedited court case to finally rule on the patent extension so generic companies could hopefully get the green light to provide an affordable form of Truvada as PrEP. Or there might just be an uprising, another historic feat Europeans are known for.