VMMC Device Developments: PrePex price drops and ShangRing gets WHO green light

In May, Circ MedTech, the makers of the PrePex device for adult voluntary medical male circumcision (VMMC), announced it would sell its non-surgical device at US$12 per unit to the 14 WHO-designated priority VMMC countries. The World Health Organization (WHO) prequalified PrePex in 2013, rendering it the first alternative to surgery available for purchase by PEPFAR and other public health providers.

For advocates following VMMC device rollout, this may sound familiar. The US$12 price has been mentioned, without written commitment, since ICASA 2013. So what does this change? Well, it means that organizations in priority countries won’t be faced with the US$20 price tag that’s been attached to the device in some pilot programs and for private purchase.

A second device, the ShangRing, was prequalified by WHO this month for VMMC in healthy males aged 13 years and older. (In contrast, PrePex is currently only officially prequalified for males 18 and older, although efforts are already underway by WHO and the company to recommend PrePex for adolescents and update the official instructions for use. Circ MedTech is also in advanced stages of adapting PrePex technology for use in infants and children.)

A VMMC “device” is an alternative to the conventional surgical methods. PrePex and ShangRing are both ring-based designs worn for a week with the aim of cutting off the blood supply through pressure, resulting in the death of the foreskin tissue. These devices eliminate the need for sutures and take less time than surgery, but the device must remain in place for a week and wound healing takes slightly longer than with surgery. Devices may be desirable for some men, could potentially simplify the VMMC experience for some and reduce the burden of labor for healthcare workers in resource-limited settings.

These device developments, however, come as VMMC programs generally are facing unexpected challenges in terms of global rollout. As AVAC covered in Prevention on the Line, the pace of VMMC is expected to drop this year in part because of scaled-back resources available from the PEPFAR program, which to-date has funded the bulk of VMMC procedures worldwide. Even with the official price reduction for PrePex and the prequalification of ShangRing, a device is only one component of any VMMC program. Whether devices will roll out depends on available funding for the overall expenses for comprehensive VMMC programs, surgical and non-surgical alike.

In terms of what a full-scale device-oriented VMMC program might look like, Rwanda continues to lead in scale-up. The country aims to circumcise 800,000 men with the PrePex device by 2016. Rwanda began routine implementation of the device in 2014 and a study presented at CROI 2015 showed 63 percent of men selected PrePex over conventional surgery. If not for stock outs of the device, study presenter and implementer Eugene Rugwizangoga (Jhpiego) posited that this number would have been higher. Overall uptake of VMMC has increased in Rwanda, aided by efficiencies such as task-shifting and mobile teams. According to Rugwizangoga, introduction of PrePex has accelerated this trend.

Zimbabwe recently included the PrePex device as part of its Accelerated VMMC Operational Plan 2014-2018 with a target of circumcising 1.3 million men by 2018. It is critical that overall funding for VMMC programming in the final PEPFAR Country Operating Plan for Zimbabwe, Global Fund and in national government investments supports the ambitious country plan.

Other countries prioritizing VMMC scale-up are in varying stages of PrePex implementation and monitoring for the type and frequency of complications that could occur outside a controlled study setting. In the VMMC device context, these two stages are referred to as active and passive surveillance. Active surveillance involves performing 1,000 non-experimental, routine device procedures and providing active follow-up for clients who fail to return for device removal. Men are monitored through home visits, in-depth interviews and genital exams. Passive surveillance is the monitoring and reporting of adverse events seen in the clinic as part of ongoing, routine service delivery.

The ShangRing device is made by Wuhu Snnda Medical Treatment Appliance Technology Company, which has marketed the device in China since 2006. More recently it was assessed in Kenya, Uganda and Zambia. Similar to its guidance on PrePex, WHO recommends that training resources for health providers are made available and that men (and adolescents) and caregivers receive accurate information on its use. WHO also endorses a one- to two-year safety data follow-up on ShangRing use in non-research settings.

It has been suggested that the ShangRing device will sell for around US$8 per unit in priority VMMC countries as part of comprehensive HIV prevention programming. With this new device entering into programs, it will be important to watch both the donors and the manufacturers to understand how procurement volumes and pricing evolve for both devices, as well as other devices in development.

It also remains unclear what role devices will play in VMMC programs in general. Though the pace of VMMC scale-up has doubled each year since 2011, exceeding targets and reaching over 9 million circumcisions, funding commitments have begun to decline. VMMC in sub-Saharan Africa is experiencing a contraction. PEPFAR, the primary underwriter of VMMC, has not set new targets and its funding has shrunk. Furthermore, reports suggest that countries are not seeking funds through Global Fund grants to fill the gap left by PEPFAR. And UNAIDS prevention targets, including for VMMC, have yet to see the light of day.

The big lift now is to ensure political will to support the continuation and even expansion of VMMC programming in its entirety. If not, we could soon see clinics shuttered and newly invested infrastructure come undone. New cases of HIV that might have otherwise been prevented will occur. This makes little financial or public health sense. Countries should be resourced to perform at current or even expanded capacity – with strategic investments in devices as well as overall VMMC programs.

From Abuja to New York City, an LGBT Activist Story

This first appeared on Whitehouse.gov. Micheal Ighodaro is being honored as a White House Champion of Change for World Refugees.

I have been thinking about all the Champions out there—President Obama, David Kato, Nelson Mandela, many like myself. I am sorry for putting myself in line with all these great champions, but if there is anything I have learned about been a champion of change, it is that when you become a champion of a particular cause you live and dream that cause and it becomes the reason why you are alive. The great Muhammad Ali said, “Champions aren’t made in gyms. Champions are made from something they have deep inside them – a desire, a dream, a vision.”

Growing up in a country like mine with a parent who was really struggling with the idea of who I was or I wasn’t, I was forced to leave my parents’ house at the age of 17. I dropped out of school and ended up in the street like several others. I was living in a room with four other young gay men. The oldest was 18. We struggled to take care of ourselves, doing unspeakable things to survive. Activism isn’t just a title. These experiences defines why I call myself an activist because being an activist means more than fighting for Gay rights, it is about survival.

After I attended the International AIDS Conference in 2012, a media organization based in the US decided to amplify my story more than I would have liked or wanted. This made it too dangerous for me to live in Nigeria. I moved to New York not sure of where I was going to stay or how I would eat. I got to this city I now can proudly call home with just a single bag. I moved from couch to couch, staying with well-meaning friends who have now become family.

I moved to more permanent housing just after a month after I got to New York. But then this well-meaning person who offered me his home was shot and killed in the streets of Brooklyn. I was shocked beyond words. I was then introduced to Housing Works, which is a non-profit organization based in New York. Housing Works got me an emergency housing, linked me to some legal assistance so I could start my asylum application process, and got me temporary medical insurance. They did all this without pre-planning or having the funds for it.

The housing they got me soon became a room for two, because as the days went by the number of LGBT asylum seekers grew. As these new asylum seekers were introduced to the “rushed and unfunded asylum program’” at Housing Works. I starting talking to service providers in the city, filling out several forms to understand the process. Before I knew it, we had a program that was catering for 15 asylum seekers—mostly from Nigeria. I am proud to say that as of today the program has almost 40 asylum seekers who are being provided stable housing and other services. Access to health care including treatment for HIV is a key part of those services. I am proud to be working at an organization called AVAC to help end AIDS among LGBT Africans and all people.

My refugee application process took less than three months, but I have friends who have taken about two years just to get an interview with the immigration officer. Some are detained for months and sometimes years. These are part of issues we still need to address in our efforts to reform the immigration system. The efforts of Housing Works in New York and the great work that Immigration Equality continues to do needs to be supported and funded because they are on the frontline of saving our lives and providing us an opportunity for a new life in America.

South Africa 4 Rectal Microbicides: A Stakeholder Consultation on Research and Advocacy

The rectal microbicide pipeline and how to proceed.

As the first phase II rectal microbicide study, MTN 017, wraps up, the prevention field is poised to consider what’s next. Some key considerations are: As highly effective oral PrEP becomes available, how will a rectal microbicide fit into combination prevention? And what might be the best rectal microbicide candidate?

The lead rectal tenofovir-based candidate is not the most potent against HIV in the test-tube. Other compounds look better in these “in vitro” analyses, giving researchers hope that they might also provide protection in humans. But clinical trials are needed to get real answers. Previous studies have shown that vaginal tenofovir gel can lower HSV-2 risk in women but other compounds in early research, such as Griffithsin, are active against HIV, HSV-2 and HCV. There are also questions about what types of delivery systems are most desirable and effective—gel, enema, nanofiber, quick-dissolving tablet, etc.

IRMA and AVAC convened a stakeholder consultation at the South African AIDS Conference in Durban, in June, to grapple with these very issues. South African advocates, clinicians and researchers weighed in, declaring the desire for more prevention options and helping to shape an agenda in support of the development of safe, effective, acceptable and accessible rectal microbicides for men, women and transgender individuals. The consultation was held in collaboration with the Desmond Tutu HIV Foundation (DTHF) and the Microbicide Trials Network.

IRMA and AVAC are pleased to share with you the six detailed PowerPoints presented by Ian McGowan and Ross Cranston of the Microbicide Trials Network, José Romero of the Population Council, Brian Kanyemba of the Desmond Tutu HIV Foundation, and Jim Pickett of IRMA. DTHF researcher Linda Gail Bekker co-chaired the event with Pickett.

Check them out here: rectalmicrobicides.org/community.php and below.

A History-Making Day

Mitchell Warren is Executive Director of AVAC.

You all undoubtedly have seen — and celebrated — the US Supreme Court rulings on health care yesterday and marriage equality today! In the midst of many other global and domestic struggles, including recent tragedy in Charleston, SC, we need to draw energy from victories. You will also have seen many press releases on both rulings from many organizations; that is not our style, but know that we are celebrating and applauding.

Those of us in the office watched President Obama speak from the Rose Garden, and he quoted one of my favorite speeches of all time — Bobby Kennedy speaking at the University of Cape Town in June 1966:

“Each time a man [editorial note: today I am sure he would have said “person”] stands up for an ideal, or acts to improve the lot of others, or strikes out against injustice, he sends forth a tiny ripple of hope, and crossing each other from a million different centers of energy and daring those ripples build a current which can sweep down the mightiest walls of oppression and resistance.”

I highly recommend viewing the full speech by RFK—check out this opening:

“I came here because of my deep interest and affection for a land settled by the Dutch in the mid-seventeenth century, then taken over by the British, and at last independent; a land in which the native inhabitants were at first subdued, but relations with whom remain a problem to this day; a land which defined itself on a hostile frontier; a land which has tamed rich natural resources through the energetic application of modern technology; a land which once imported slaves, and now must struggle to wipe out the last traces of that former bondage. I refer, of course, to the United States of America.”

Now more than ever: Much accomplished; much to do!

Mitchell Warren
Executive Director, AVAC

AVAC Team Member Honored at the White House: A champion of refugee rights

On June 25, Micheal Ighodaro, an AVAC team member and leading activist for the rights of LGBT activists, was honored by the US government as a “Champion of Change” for the rights of refugees. In a ceremony at the White House, Micheal was recognized for his vocal advocacy for the rights and needs of men and women who are subject to persecution, discrimination and violence because of who they love—and who too often find themselves forced to leave their countries of origin, navigating new cultures, health and housing systems, as well as the process of obtaining asylum.

As policy and program assistant at AVAC, Micheal is working with allies across sub-Saharan Africa to define agendas that address health and human rights for all. A video of the panel discussion featuring Micheal and his fellow honorees can be viewed here, details of all the champions are available now; and a blog post from Micheal about his experiences as a refugee, activist and proud gay man is available on the White House website!

AVAC is proud to work with Micheal and salutes all of the champions recognized today.

Preparing for IAS 2015: Key satellites, prevention roadmap and more

Next month the IAS Conference on HIV Pathogenesis, Treatment and Prevention will take place from July 19 – 22 in Vancouver, Canada.

Held every two years, this year’s conference will cover the results from several important studies, including a special symposium on the START trial; final results from HPTN 052; and important findings from several PrEP studies and projects. The full conference schedule is available on the IAS 2015 website and AVAC has pulled together a HIV prevention roadmap, sortable by timing, intervention and session type (also available as a PDF). IAS also has a one-pager on biomedical prevention activities at IAS.

In addition, we wanted to be sure to draw your attention to several satellite sessions that AVAC and partners are leading at IAS 2015 that are of particular interest to prevention advocates:


  • Creating Rectal Microbicides People Desire: How do we get there?, 12:30–14:30, Room 121-122
    With the recent completion of enrollment into the first-ever Phase II safety and acceptability study of a rectal microbicide (RM) for HIV prevention, many questions remain about future directions for the RM research agenda. Indeed, the opportunities and challenges posed by conducting a Phase 3 RM study are multifaceted. This session will include a panel of scientists, advocates and research participants who will share the latest information on RM science and discuss next steps in the development of RMs to prevent new HIV infections associated with anal sex.
  • Injectable Options and Preventable Confusion: An updated and interactive discussion on the pipeline of antibodies, long-acting ARVs and vaccines, 14:45–16:45, Room 121-122
    As trials of varying “injectable prevention” options are moving ahead in similar populations, countries and trial sites, it is key for policy makers, researchers, regulators and advocates to understand the distinctions between the options. This interactive session will provide overview presentations on the major areas of work (preventive vaccines; long-acting injectable antiretrovirals; and passive immunization strategies with broadly neutralizing antibodies), followed by a panel discussion to explore issues related to trial design, community engagement and ethics. (Coffee and light snacks provided.)
  • What's Next for HIV Vaccines: From design to efficacy testing, 17:00–19:00, Room 121-122
    The HIV research field is rapidly evolving and includes several vaccine strategies for prevention or therapy. This session will explore the latest in vaccine design, development and testing. The goal of this session is to examine the diverse, cross-platform approaches that are currently being vetted for vaccination and other approaches to help end the HIV epidemic.


  • Minor Issues, Major Consequences: Ensuring Adolescents’ Access to Proven Prevention Methods, 18:30–20:30, Room 109
    If the dapivirine ring is found safe and effective in ASPIRE and The Ring Study and subsequently approved, it would be a triumph for women. Yet, women under 18, who are among those at highest risk, could be left out, absent safety data in adolescents. This session will review ethics, informed consent, law and regulations around adolescents in clinical research, and the urgent need for new HIV prevention options for adolescents.

For those not attending the conference in person, there are a number of ways to follow along at a distance. In addition to AVAC’s online commentary on Twitter and Facebook to can follow the official conference hashtag – #IAS2015.

Official online scientific coverage will be provided by Clinical Care Options and NAM. Sign up to receive email bulletins from NAM.

Stay tuned for additional updates as the conference draws nearer, and we welcome questions and comments at avac@avac.org.

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!”

Keeping an Eye on Phylogenetics

Heeyoung Sohn is an AVAC staff member.

Last week, the New York Academy of Sciences brought together researchers and public policy makers for a conference on phylogenetics. As someone who is not a biologist or researcher, I quickly learned that phylogenetics is using genetic sequences to tell a story about how groups or organisms evolved from a common ancestor and/or how they are related to one another. In fact, we hear about phylogenetics all the time when scientists talk about the evolution of humans or even when we draw a family tree. But it isn’t just human genetic material that gets run through phylogenetic analyses. Viruses have genomes, too. The purpose of this conference was to discuss the state of the art in the ongoing investigation of how phylogenetic analyses are being used in the context of HIV.

Phylogenetic analyses of HIV use sequenced viral genomes, along with a complex set of assumptions and statistics to develop “family trees” for groups of viruses. This approach has been used to pinpoint the strains of SIV—the simian form of HIV—that likely made the leap from non-human primates to humans, to begin the epidemic many decades ago. And it is being used now to understand the origins and geography of particular strains, study drug resistance and so much more.

HIV is highly genetically variable. It copies itself over and over again and makes countless small errors. This means that evolutionary trees don’t stretch over decades, but over weeks or months. Scientists can use phylogenetics to track clusters of new cases of HIV, even potentially identifying the individual who is the source of the virus that was then passed on to others in the community. It’s important to remember, though, that phylogenetic analysis isn’t fool proof. It generates viral “family trees” based on a set of assumptions and statistical analyses, and these can be wrong.

On one level, phylogenetics sounds like a powerful tool for fighting the virus. In geographic areas where HIV testing has identified high rates of new cases, researchers can pinpoint the specific locales and even individuals associated with these “hot spots.” (HIV testing gives you an idea of where a hot spot is, but because people can travel to testing centers and may even intentionally choose to go somewhere other than where they live, the sites that find many new cases may not always reveal where the new transmissions are happening.) Researchers propose that phylogenetics could be used to project incidence rates in a given area and even calculate the likelihood of an individual from that area acquiring HIV.

So far, most phylogenetic analyses are focused on understanding what has happened in a community—not predicting the future. For instance, one phylogenetic study presented at the conference focused on HIV transmission in the Netherlands, which has seen a resurgence in HIV despite the widespread use of antiretroviral therapy. The study mapped and tracked HIV transmission in gay men and men who have sex with men, and found that both well-established networks and the continual addition of new networks drive the HIV epidemic.

However, phylogenetics is a double-edged sword and advocates at the meeting pointed out that there are issues to track closely as the field develops. Joanne Csete of Columbia University highlighted the potential risks to and violations of human rights that could happen if phylogenetics was used to pinpoint specific areas and/or at-risk populations. Mark Harrington, from the Treatment Action Group, discussed the importance of language and how dangerous the phrase “who infected who” can be when talking about phylogenetics, as people or groups can become targets for abuse.

This erroneous linking of people is a real threat as the world recently saw Michael Johnson, a university student, accused of infecting others with HIV, without any evidence. Although phylogenetics was not used, Johnson’s case shows how quick people are to link HIV infections to specific individuals despite the lack of evidence. As the UNAIDS guidance on HIV criminalization writes, “HIV phylogenetic evidence alone is not sufficient to establish, to the required criminal law standard, that one person did infect another person with HIV.”

Phylogenetics also has the potential to drive funding to only certain areas or groups and cause others to fall through the cracks that also are in need of prevention, treatment and testing. The science behind phylogenetics is complex, leaving room for potential misinterpretation of results.

It is no doubt that phylogenetics will play an important role in the future of HIV/AIDS. Advocates and their allies need to track this evolving field to ensure that efforts to pinpoint genetically linked cases don’t end up putting targets on specific communities or even individuals. It’s essential, as always, to ensure that research and methods which can be used for improving the fight against HIV/AIDS do not violate human rights and are clearly explained, so that the overall response stays on track. To read a phylogenetic case study, click here.

Notice of Intent to Publish a Funding Opportunity Announcement for Adolescent Medicine Trials Network for HIV/AIDS Interventions(ATN) Research Program Grants(U19)

The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN), with the mission to reduce new HIV infections among at-risk youth and improve retention across the HIV care continuum among HIV-infected adolescents and young adults in the United States, released Notices of Intent to Publish a Funding Opportunity. The two notices are available at http://grants.nih.gov/grants/guide/notice-files/NOT-HD-15-017.html and http://grants.nih.gov/grants/guide/notice-files/NOT-HD-15-018.html.

Announcing the Call for 2016 AVAC Advocacy Fellows