Science, Solutions and Questions at Vancouver IAS Conference

“Science has delivered solutions. The question is: When will we put it into practice?”

So says the last line of the Vancouver Consensus Statement, a stirring call for expanding access to antiretrovirals for treatment and prevention as part of a comprehensive response to AIDS. AVAC signed the statement, released at the start of this year’s conference of the International AIDS Society. So did virtually every notable scientist and physician in the field. And we firmly believe in the contents of the statement.

Over Sunday and Monday pre-conference satellite sessions and in the official program, we heard a lot of science. On Monday, there were presentations of data from HPTN 052 and START—two complementary trials of ART in people living with HIV. There were also data from the ADAPT and IPERGAY PrEP trials and a press conference looking ahead to news from later this week.

For all of this, the Vancouver Consensus Statement is the backdrop—as is the news, released by UNAIDS just prior to the launch of the conference, that the global total of people initiated on ART has exceeded 15 million, and that incidence has begun to drop in some places.

Overall, it is a very good time to be on the side of scientific solutions to the HIV pandemic. And that’s where AVAC stands. But listening closely at the conference and in recent months, we’d offer this additional formulation of the consensus statement’s closing line: “Science has delivered the questions. The solution is: Not shying away from the answers.”

One of the primary solutions that science has delivered is the use of antiretroviral therapy for people living with HIV, both for their own health and to reduce the risk of onward transmission. In a special presentation on Monday (The Strategic Timing of Anti-Retroviral Treatment (START) Study: Results and Their Implications (Monday 20 July, 11:00-12:30), Jens Lundgren (University of Copenhagen) presented data from the START trial, which showed significant benefits for people living with HIV who started ART regardless of CD4 cell count, versus those who started treatment as indicated by the guidelines where they lived. As described in May, when data from the study were first reported, immediate initiation more than halved the risk of serious adverse events, serious non-AIDS events, or deaths.

This is the first major meeting since the START data started making waves (between START and PrEP, this may be the most pun-able conference to date), reaffirming global campaigns to expand ART coverage and to make ART the cornerstone of efforts to end AIDS.

If START has a twin, it is HPTN 052, which also saw data presented on Monday. Mike Cohen (UNC and HIV Prevention Trials Network) delivered the complete findings from HPTN 052, which first reported interim results in 2011 (View slides and abstract via the Conference Programme, session MOAC01: TasP: Just Do It. Monday 20 July, 11:00–12:30)

In that preliminary report, immediate initiation of ART (in this trial, at CD4 cell counts above 350) dramatically reduced the chances that an individual would pass HIV to his or her primary partner.

In the data Cohen presented here, the initial finding holds true. Over the course of the trial, there were eight “linked” transmission events (where the virus acquired matched that of the partner enrolled in the study) in couples where the HIV-positive partner had initiatied ART. Where transmission did occur, it usually happened in the context of incomplete virologic suppression—either a person had started ART too recently to be completely suppressed or because of adherence challenges.

The bottom line: virologic suppression makes HIV transmission between individuals where one person is living with HIV and the other is not highly unlikely. The treatment that has a prevention benefit is also good for the individual—so on every count, the science appears to have provided the solution.

And yet. The real world is a decidedly unscientific place.

In HPTN 052, there were 26 unlinked transmission events, where a person with a known HIV-positive partner acquired HIV from outside the primary partnership followed in the study. So having one partner who is virologically suppressed isn’t protective for an HIV-negative person who, for a variety of reasons, may have other partners and/or other sources of risk, such as injection drug use.

This reality is one of the many places where science and social, cultural and personal realities demand multiple solutions. The number of unlinked cases of HIV is a reminder that people exist in complex realities, with multiple partners and various behaviors.

Another powerful reminder of this context came at a pre-conference satellite on the global status of women’s access to ART. That session presented preliminary findings from an ongoing investigation commissioned by UN Women and carried out in collaboration with the ATHENA Network, Salamander Trust and AVAC. Combining a participatory methodology in which women living with HIV defined, delivered and assessed questions about health care experiences and an in-depth literature review, the work to date shows that women are being reached by ART but that the rights-based framework that allows them to remain on ART after initiation is, in many instances, lacking.

What to do with these data?

One answer does lies in science. Earlier this year, at the Conference on Retroviruses and Opportunistic Infections, the investigators of the Partners Demonstration Project presented the results of their combination PrEP and treatment study in which the HIV-negative member of a serodiscordant couples was offered PrEP as a “bridge to ART” for the person living with HIV. Right now, the data say that PrEP reduces risk of HIV acquisition regardless of who your partner is or how many partners you have (for more on PrEP, see below). And it turned out that, over the course of the study, very few new cases of HIV occurred. For 48 percent of the time, couples were using PrEP alone. PrEP and ART overlapped during 27% of the time, ART was used alone 16% of the time, and neither was used 9% of the time.

WHO did not formally publish their new ARV guidelines at this meeting. However, Gottfried Hirnschall, who directs WHO’s HIV department, did say that additional formal guidance on both PrEP and ART would be released by the end of the year. It is even possible that “rapid advice” could be available sooner—perhaps even in a matter of weeks. Hirnschall anticipated that these new ARV guidelines would recommend the offer of treatment for all adults and adolescents regardless of CD4 count as well as PrEP being offered as an additional prevention choice for people at substantial risk of HIV infection.

As Ambassador Debbi Birx, head of the US PEPFAR program stated in her Monday morning plenary, “Don’t wait for the paper” from WHO or other agencies. “Act on the science and evidence now.”

Acting on science is, as Ambassador Birx and other speakers have noted, just part of the solution. Success depends on non-scientific solutions that are, in some cases, getting lip-service but struggling for real traction today. Women in the global survey described above consistently reported the benefit of peer-delivered treatment literacy, non-stigmatizing sexual and reproductive health care, and rights-based care for all women, including those who aren’t pregnant when they enter the health system.

The science, if we really listen, says something slightly different. It says that ART for people living with HIV and PrEP for people who are at risk, and peer-delivered treatment literacy, and rights-based health care environments for women, men, young people and all key populations can begin to end the epidemic—if and only if other strategies are scaled up at the same time.

PrEP Talk: Promising, Perplexing
Monday was also a big day for PrEP data (slides can be downloaded from the session MOAC03 from the online conference programme), with data from the ADAPT trial that evaluated various dosing strategies, including once-daily, fixed intermittent dosing and event-driven dosing. The study enrolled South African women and gay men and transwomen in Thailand and the US. Overall, people were able to take PrEP, reported principal investigator Bob Grant. Individuals who were counseled to take the drug on a daily basis had a higher coverage of sex acts than those who were advised to use a non-daily strategy. For this group, the missed dose was usually post-sex—a finding that echoes reports from women who participated in the FACTS 001 trial of 1% tenofovir gel, which also tested a coitally-related dosing schedule. In both ADAPT and FACTS 001 cases, the dose after sex proved difficult—participants weren’t at home and/or weren’t in the emotional or physical space where they felt they could swallow a pill or insert a gel.

The good news from ADAPT is that PrEP continues to be feasible and acceptable in a variety of settings and demographics—bolstering the call for this strategy to be rolled out as an additional prevention option for all individuals at high risk.

Of concern and for careful tracking by advocates, is messages coming from the podium that PrEP may not work as well for women as it does for men whose primary risk is via anal sex. It is clear that women need to take daily oral PrEP for longer periods of time before they have protective levels in their vaginal tissue. It is also clear that adhering to a daily oral regimen may be difficult for some women, just as it is for some men. But what’s happened over the past few days with casual references from NIAID Director Tony Fauci and other leading scientists is a sowing of confusion that appears to contradict the US FDA recommendation and data from the Partners PrEP and TDF2 trials that found comparable protection for men and women.

Sometimes science raises questions, and we’re all for these questions coming to light. But it’s essential that the language be clear and that the way to certainty be mapped out. Right now, the discussion feels more risky than scientific—at a time when science is supposed to reign.

New Report on HIV Prevention R&D Investment Highlights 2014 Global Funding Trends

The recent UN Report on the Millennium Development Goals (MDGs) calls out the 40 percent reduction in new HIV infections since the MDGs were established in 2000 as a singular MDG achievement1. That progress reflects 15 years of HIV research in many forms—from female condoms and voluntary medical male circumcision, to new strategies for preventing vertical transmission to the scale-up of ART. Over the years, this progress has been supported by investments from many government, philanthropic and private sector funders of HIV prevention research.

The 11th annual report on the state of HIV prevention research investment, HIV Prevention Research & Development Funding Trends 2000–2014: Investment Priorities To Fund Innovation In An Evolving Global Health and Development Landscape, suggests that this work is still on the agenda for funders, albeit with a small cohort supplying the bulk of the resources.

The new report, released in Vancouver at the IAS 2015 conference, was prepared by the HIV Vaccines & Microbicides Resource Tracking Working Group (RTWG), led by AVAC, in partnership with the International AIDS Vaccine Initiative and UNAIDS. HIV Prevention Research & Development Funding Trends 2000–2014: Investment Priorities To Fund Innovation In An Evolving Global Health and Development Landscape documents that absolute funding levels have been stable over the past few years. This reflects an overall decline in real spending given biomedical research inflation.

In 2014 funders invested a total of US$1.25 billion in research and development (R&D) for HIV prevention—representing a decrease from the 2013 funding level which totaled US$1.26 billion.

In 2014, the US public-sector and the Bill & Melinda Gates Foundation account for 83 percent of all HIV prevention R&D funding and the number of philanthropic funders engaged in HIV prevention research has continued a steadily decline since 2010. Thus, the report points to the need for a broader funding base.

Despite the slight decline in funding, HIV prevention R&D is still delivering important advances. The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Vancouver July 20-22, will showcase results for a range of groundbreaking research that has been supported over the past several years, including the Strategic Timing of Antiretroviral Treatment (START) trial, the HPTN 052 treatment as prevention trial and several groundbreaking oral PrEP trials.

Results from studies of a vaginal ring containing the antiretroviral dapivirine are expected in the next 12 months. Several different HIV vaccine candidates, neutralizing antibodies and long-acting injectable ARVs are currently in trials that could lead to multiple efficacy trials starting over the next two years.

While the report focuses on financial resources, in also highlights the essential role of individual trial participants. In 2014, there were over a million participants in HIV prevention research trials globally. With continued human and financial investment, the 40 percent reduction in new HIV infections attributed to the MDGs is hopefully only the beginning.

For more information on the HIV Vaccines & Microbicides Resource Tracking Working Group, the full report, executive summary, graphics and slides visit www.hivresourcetracking.org.

1 The MDGs consist of eight global goals, with goal six to combat HIV/AIDS, malaria and other diseases. For more information on the MDGs see: www.un.org/millenniumgoals/aids.shtml.

Px Wire July-September 2015, Vol. 8, No. 3

Px Wire is AVAC’s quarterly update covering the latest in the field of biomedical HIV prevention research, implementation and advocacy.

In this issue, we describe the calls to expand ART access to all who need it, which have been amplified over the two months since the results of the START trial. We also document a growing demand for PrEP and the need for updated guidance from the WHO and targets from UNAIDS. And we look at the increasing role civil society is playing at developing PEPFAR Country Operating Plans (COPs) which guide targets, geography, interventions and budget levels on an annual basis.

In our centerspread, we look backwards and forward, at the conferences that took place in Vancouver and Durban in 1996 and 2000 and will again this year and the next.

This issue is also available as a webpage.

Demands for PrEP, treatment scale-up, targets and more, all in the new issue of Px Wire

The latest issue of Px Wire, AVAC’s quarterly newsletter on HIV prevention research and implementation, is now available.

Click here to download the new issue.

In this issue we look back at the historic International AIDS Conference that took place in Durban, South Africa, in 2000, how far we’ve come in the response today—and how much further we still need to go.

When the AIDS community gathered in July 2000, the world was still four years away from anything resembling global antiretroviral therapy (ART), but through the activism seen at that conference, the agreement that ART was a human right started then and there. There has since been remarkable scale-up and innovation in the use of ARVs as both treatment and prevention.

This issue of Px Wire describes the calls to expand ART access to all who need it, which have been amplified over the two months since the results of the START trial, which found that initiation of ART in people living with HIV significantly reduced serious clinical events and deaths as compared to people who initiated ART based on the guidelines in their countries.

We also document a growing demand for PrEP, including a robust and spontaneous show of support for expanded daily oral PrEP access for all those at risk by participants at the recent South African AIDS Conference, and the need for updated guidance from the WHO and targets from UNAIDS.

In our centerspread, we again look backwards and forward, at the conferences that took place in Vancouver and Durban in 1996 and 2000 and will again this year and the next.

And we look at the increasing role civil society is playing at developing PEPFAR Country Operating Plans (COPs) which guide targets, geography, interventions and budget levels on an annual basis.

Pre-Exposure Prophylaxis for Prevention of HIV Infection

This column first appeared in the Zambia Post.

Three years ago, the HIV and AIDS world received news that the authoritative US Federal Drug Authority (FDA) had approved the use of the antiretroviral combination pill Truvada by HIV negative people to reduce the risk of acquiring HIV infection (Truvada combines the two ARVs Tenofovir and Emtricitabine and is often shortened to TDF/FTC).

Within days of this announcement, the WHO issued its GUIDANCE ON PRE-EXPOSURE ORAL PROPHYLAXIS (PrEP) FOR SERODISCORDANT COUPLES, MEN and TRANSGENDER WOMEN WHO HAVE SEX WITH MEN AT HIGH RISK OF HIV: Recommendations for use in the context of demonstration projects.

The FDA approval, and the WHO guidance, followed results from clinical trials that showed that the daily taking of ARVs (specifically Truvada) by HIV negative people (men and women) exposed to HIV infection, significantly protected them from the acquisition of the virus.

One such study, the PARTNERS PrEP Trial, was done in Uganda and Kenya and involved 4,758 HIV-discordant couples (in which one partner was HIV infected and the other negative). The trial showed that if the HIV negative partner took daily Truvada, they were 75 percent less likely to become infected (than those who took a daily pill that did not contain Truvada or any other ARV). Adherence to taking the Truvada daily was important in improving the protection it offered. Amongst those HIV negative partners who showed that they were complying with taking the drug daily (as demonstrated by the presence of detectable medicines in their blood, PrEP reduced their risk of HIV infection by 90 percent).

Another study, known as the iPrEx Study, was also done among men and transgender women who have sex with men. It was done in Peru, Brazil, Thailand, South Africa and the United States. In that study, those HIV negative people who were given PrEP were 44 percent less likely to get HIV infection, than those who were not. In those men who took their pills consistently (as evidenced by blood tests) PrEP reduced their risk of HIV infection by as much as 92 percent.

The clinical trials demonstrated that taking the PrEP consistently daily is key to achieving high levels of protection from infection.

In its guidance on PrEP, the WHO was characteristically cautious in its advice to governments, stating: “Although the evidence of effectiveness is strong, it remains unclear how PrEP may be implemented and scaled up in settings where its use might be most beneficial.”

The guidance also stated that WHO was encouraging countries to undertake demonstration projects, and would “offer advice on key questions and areas that could be addressed to facilitate understanding of the safety, effectiveness and sustainability of oral PrEP, and its use as an addition to existing HIV prevention efforts”.

“The outcome of these demonstration projects and country experience will also be used by WHO in 3 to 5 years time to develop guidance for the implementation and scale up of PrEP,” the 2012 WHO guidelines promised.

The guidelines’ specific recommendation on PrEP for serodiscordant couples says: “In countries where HIV transmission occurs among serodiscordant couple, where discordant couples can be identified and where additional HIV prevention choices are needed, daily oral PrEP (specifically tenofovir or the combination tenofovir and Emtricitabine) maybe considered as an additional intervention for the uninfected partner”.

In May last year, the United States’ Public Health Service released its comprehensive clinical practice guidelines for PrEP called ‘Pre-exposure Prophylaxis for the prevention of HIV infection in the United States-2014″.

These guidelines stated at the end of a review of the PrEP trials in men and women; “Daily oral PrEP with TDF/FTC is recommended as one HIV prevention option for heterosexually active men and women at substantial risk of acquisition because these trials present evidence of its safety and to present evidence of efficacy in these populations, especially when medication adherence is high”.

Similar recommendations are made for sexually active MSM and injecting drug users.

Notably, both the WHO guidance and the CDC-led US Public Health Service clinical practice guidelines emphasize that PrEP cannot and should not be taken in isolation, or as replacement of existing prevention efforts and methods. Both stress that PrEP should be used as “one prevention option” that should be “an addition to existing HIV prevention efforts”. This is highly significant because even while on PrEP, HIV negative people should continue using condoms; reduce on multiple concurrent sexual partnerships etc.

So what are the implications of PrEP, prevention of new HIV infections in Zambia, and the general Zambian HIV and AIDS response?

Issues of the paucity or lack of domestic funding of our response aside, there is a deafening lack of noise on PrEP in our national HIV and AIDS conversation. Since the FDA approval and the subsequent issuance of WHO guidelines, we have heard more spoken around Option B+, Test and Treat, VMMC, sex work and sex workers, defining key populations, getting Zambia to zero new infections and so on. Even this column has referred to PrEP mostly in passing and in context of other HIV prevention subjects.

One wonders if perhaps the silence on PrEP has been fueled by the international publicity and discussion around the iPrEx study and its results implications for preventing HIV infections among men who have sex with men. Has Zambian officialdom’s fear of recognizing the existence of Zambian MSM and transgender people clouded or completely blacked out a potentially beneficial addition to our armamentarium of evidence-based and proven HIV prevention interventions?

Some of the seminal work on serodiscordance in married and cohabitating couples has been done here in Zambia. In our fear of addressing MSM issues and related HIV, are we denying serodiscordant couples in Zambia an intervention that is available now to similar couples in the US, using a drug combination that is available and approved for treatment in Zambia?

The least we can do and bring up to the public arena the fact that PrEP works is that we should be debating the pros and cons of its implementation as a nation!”

Demanding PrEP at SA AIDS 2015: Scenes from an Activist “Smackdown”

Fifteen years after activists marched for HIV/AIDS treatment access at the International AIDS Conference in Durban in 2000, a group of South African activists are demanding access to PrEP for HIV prevention as an option for all South Africans who need and want it.

In a statement issued today, activists called for swift action to get daily oral Truvada as PrEP approved for South Africa and to expand access to PrEP for all who need it. They also warned against anti-PrEP propaganda noting that, “As South Africans, we know too well the human cost of misinformation about HIV and of waiting too long to implement life-saving, evidence-based HIV interventions. We call on the MCC of South Africa and the Department of Health to prioritize enabling access to this HIV prevention medication.” (Full statement available here.)

Shortly after the statement was finalized, International AIDS Society president Chris Beyrer delivered a plenary address at the South African AIDS Conference (SA AIDS), during which he—as one advocate in the audience described—offered a “a full-throated endorsement of PrEP, made a specific call for PrEP in Africa, South Africa, and called to task PrEP denialism”. He even presented a summary slide of the local activists’ statement:

The activism continued into the evening as activists crowded the room during a satellite session and voiced their support for PrEP in South Africa (and beyond) and brought clarity and facts to a discussion on PrEP data, feasibility in the South African context and the true need and wants of communities on the ground.

Long-time AIDS treatment and prevention activist Peter Staley described the activists’ comments in a POZ blog and pictures and quotes from the action from Twitter are summarized here.

Check back on the P-Values blog for more from the conference and voices from local activists and partners moving the HIV prevention research and implementation agendas.

South African AIDS Activists Demand PrEP Now

Durban, KwaZulu-Natal, South Africa — South African advocates call for Truvada as Pre-Exposure Prophylaxis (PrEP) to prevent HIV infection to be made available to all those who need it now. Truvada as PrEP is an effective and safe medication that has been proven to reduce the risk of HIV infection for all populations. Clinical trials from a multitude of respected institutions and physicians have shown that PrEP works when taken as directed.

As the 7th SA AIDS conference gets underway in Durban, a diverse collection of advocates have assembled to call on the South African Medicines Control Council (MCC) to immediately approve the use of Truvada PrEP. PrEP must be made available and accessible to South Africans who are at heightened risk of infection, and would benefit from an additional tool to prevent HIV. South Africa is the most impacted country by HIV in scope and scale. To turn around our epidemic, South African young women and girls, gay men, sex workers, and people who use drugs need PrEP as an additional HIV prevention option.

We, South African advocates, are alarmed to see the AIDS Healthcare Foundation (AHF), an American-based chain clinic and pharmacy that has led the charge in PrEP Denialism, participate at the Durban Aids Conference. The AHF has consistently opposed PrEP using faulty science and fear mongering and has failed to accept extensive research that has clearly and repeatedly shown PrEP to be safe and efficacious. South Africa can only allow evidence-based health policy and implementation. Denialism thrown in the face of facts and research can never be allowed again. As South Africans, we know too well the human cost of misinformation about HIV and of waiting too long to implement life-saving, evidence-based HIV interventions.

We call on the MCC of South Africa and the Department of Health to prioritize enabling access to this HIV prevention medication. Over 1,200 infections occur in South Africa each and every month. It is imperative that we use every option available to reduce new HIV infections, thereby reducing the number of people who will spend their lives on ARVs.

For more information please contact:

PrEP Funding Opportunity Announcement

Through the Corporate Grants program, Gilead is looking to support efforts of community-based organizations, public health entities and similar umbrella organizations focused on high-risk populations to educate their constituents and healthcare providers about the role of PrEP as part of comprehensive HIV prevention. Gilead will consider a wide range of ideas that reach diverse geographic locations within the United States.

 

Find out more by visiting:  http://hivdatf.org/2015/06/02/pre-exposure-prophylaxis-prep-for-hiv-prevention-funding-opportunity-announcement/

After FACTS: What’s next for HIV prevention in women?

FACTS 001, which released data at CROI, found no evidence of protection overall associated with the vaginal gel. Partners Demonstration Project, which reported data at the same meeting, found that serodiscordant couples using oral PrEP and/or ART had very low levels of HIV transmission. In this webinar, we discussed what these and other data meant for women, including young and adolescent girls.

Government Should Give Guidance on Drugs that Prevent HIV

This piece by a 2014 AVAC Fellow marks the latest efforts by Ugandan civil society to secure pre-exposure prophylaxis (PrEP) access. Author Charles Brown is an advocate, based at the Infectious Diseases Institute (IDI), who spent the last year and a half advocating for PrEP rollout for groups at high-risk of HIV infection including young women, sex workers, men who have sex with men and serodiscordant couples in Uganda. Read his article here.