PrEParing to Prevent HIV

Kenya strikes out as a leader in offering a recently proven HIV prevention method to men who have sex with men and others at risk of contracting the virus.

By Mary Rushton

In May, the Kenyan government launched a nationwide program making pre-exposure prophylaxis or PrEP—the use of daily antiretroviral drugs (ARVs) to prevent HIV infection—available to 500,000 individuals over five years to reduce their risk of acquiring the virus.

The 84-page PrEP implementation plan, developed with the help of over a dozen national and international partners, is the country’s latest weapon against an epidemic that while waning, is still stubbornly persistent. Oral PrEP will be available in 28 of Kenya’s 47 counties that account for 90 percent of the country’s HIV/AIDS cases.

The East African country has also taken the unusual step of combining PrEP rollout with an unprecedented effort to make HIV self-testing kits available through public and private health facilities and select pharmacies for around US$8 each. The aim of the so-called “Be Sure” campaign is to try and remove common impediments, including stigma, inconvenience, concerns over confidentiality, and lack of transportation that discourage men who have sex with men (MSM), female sex workers (FSWs), and other individuals at elevated risk of contracting HIV from getting tested.

Kenya hopes to reduce the number of HIV infections among adults by an astounding 75 percent within two years, but to do so will require heavy-duty outreach and implementation of PrEP to anyone at substantial risk of contracting the virus, including those whose behaviors run counter to sodomy laws that date back to the British colonial era.

PrEP efficacy

The use of the ARV Truvada—a single pill combination of the ARVs tenofovir and emtricitabine—was first proven 44 percent effective at reducing HIV infection rates in a randomized, double-blinded placebo-controlled trial of 2,500 MSM and transgender women who have sex with men from the US, Brazil, Ecuador, Peru, South Africa, and Thailand (N. Eng. J. Med. 363, 27, 2587, 2010). Two subsequent trials conducted in Europe, which were not placebo controlled, established Truvada’s efficacy at 96 percent in preventing HIV infection in MSM and transgender women. Together, these trials led to the approval of oral PrEP by US and European regulatory authorities.

PrEP is now part of an array of HIV prevention options available in Kenya. Others include condoms, adult male circumcision, risk reduction counseling and testing, and treatment as prevention—the early initiation of ARVs to not only treat the virus, but also reduce the rate of viral transmission (see Guidelines on Use of Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Kenya, NASCOP, 2016 edition).

Kenya is not the first country to put in motion efforts to increase PrEP use. In December 2015, South Africa approved Truvada for use as PrEP by MSM, transgender persons, heterosexual men and women, adolescents, and injection-drug users (IDUs; S. Afri. J. HIV Med. 17(1), Art. 455, 2016). Five months earlier, the US made Truvada part of its National AIDS Strategy for HIV prevention for MSM, transgender women, serodiscordant couples (those in which one partner is HIV infected and the other isn’t), and “others documented to be at elevated risk of acquiring HIV through sexual activity” (see The National HIV/AIDS Strategy: Updated to 2020, White House Office of National AIDS Policy, July 2015). France also began offering PrEP within its national health care system in January 2016.

What is surprising about Kenya’s PrEP program is the level of engagement within the MSM community. Like prostitution and injecting drugs, homosexuality is considered illegal under the Kenyan Penal Code, punishable by up to 14 years in prison. Yet Kenyan authorities are remarkably forward thinking when it comes to recognizing the drivers of the HIV epidemic in their country and in implementing programs to help halt its spread.

“Kenya is really showing leadership here and that is encouraging,” says Chris Beyrer, an epidemiology professor at Johns Hopkins University and former president of the International AIDS Society (IAS). “In 2013 we did a regional meeting on MSM in Africa that Kenya agreed to host. It was very striking that the national and local officials came. The physician who was heading the key populations program at the time for the Kenya Ministry of Health was very outspoken, saying that Kenya has a high burden of HIV and that they needed to do better and needed to consider PrEP. Most governments were not willing to say those kinds of things even if researchers were already saying that.”

Even more than a decade ago, while most countries in Africa were overlooking MSM in assessing the impact of the epidemic, the US-based Population Council in New York surveyed the sexually transmitted infections (STIs) and HIV risk of MSM in Kenya with the blessing of Kenyan hospitals and research institutions. Recognition of stigmatized communities grew from there. In 2010, the government in partnership with the Joint United Nations Programme on HIV/AIDS (UNAIDS) hosted the first national symposium for key populations in Mombasa at risk for HIV/AIDS, including MSM. That same year the country’s health secretary launched a website offering MSM sensitivity training for Kenyan health care workers.

This outreach with the MSM community has not always been well received, however. Researchers in Kenya have faced retribution. Seven years ago, angry mobs descended upon an HIV clinic in the coastal town of Mtwapa and attacked it for its involvement in MSM research. Then in 2014, police raided and arrested workers at a men’s health and HIV/AIDS advocacy organization in Kisumu for illegally “practicing sexual orientation information” (Nature 509, 274-275, May 15, 2014).

Still, Kenya stands apart from some of its neighbors. Uganda recently set in motion a Anti-Homosexuality Act that includes life sentences for adult consensual same-sex relationships (In Brief, IAVI Report, Vol. 18, No. 1, 2014), and last year Tanzania banned HIV/AIDS outreach projects aimed at gay men (Washington Post, Nov. 23, 2016). The many research partners working to implement Kenya’s Ministry of Health and National AIDS and STI Control Programme have recognized that MSM are a key population and have demonstrated their willingness to work with diverse groups (PloS One 10:e0137007, 2015). This level of engagement between healthcare workers and at-risk communities have carried over to the PrEP discussion.

An editorial published two years ago noted that in a continent decimated by AIDS, Kenya has been a leader in recognizing the health needs of stigmatized populations that feared legal authorities and had virtually no access to health services (AIDS 29, (Suppl. 3) S195-S193, 2015). One of the editorial’s authors is Eduard Sanders, a public health physician and epidemiologist who works with the Kenya Medical Research Institute-Wellcome Trust Research Programme (KWTRP). He says that although the country criminalizes homosexuality, its constitution entitles health care for all citizens. Sanders, who is a principal investigator of several observational studies involving mostly MSM and FSW in the Kilifi County, is receiving support from the Kenyan government to work with these at-risk communities. He established a long-running cohort of MSM and FSW in 2005 with support from IAVI and, to date, has tested more than 1,500 MSM, enrolling 950 in studies examining HIV incidence and disease progression.

Sanders’ work in HIV began in Ethiopia in 1999, where he and several of his fellow scientists from Amsterdam were invited to set up a research laboratory in Addis Ababa to assist in the development of an AIDS vaccine. But it wasn’t until he joined KWTRP in 2003, and helped to establish the District Hospital HIV Care and Research Programme in Kilifi, that he began working with the MSM community. Unlike in the US, where a vocal MSM community pushed to accelerate the development of ARVs at the dawn of the AIDS epidemic, the MSM population iHIV Greenn Kenya, like those in other sub-Saharan countries, were largely suffering in silence. Enrolling MSM into cohort studies investigating the feasibility of an HIV vaccine, which the clinical research facility was approved for in 2005, was unchartered territory.

Sanders says they began by dispatching individuals into areas where MSM engaged sex clients to do outreach. Gradually the cohort grew and today is arguably one of the best sources of information about MSM in all of sub-Saharan Africa. One of their initial studies, published just two years after the cohort started, showed HIV prevalence rates were 12.3 percent among men who have sex with men and women, and an astounding 43 percent among men who have sex with men exclusively, possibly due to an even higher rate of recent unprotected receptive anal intercourse (AIDS 21, 18, 2513, 2007). Later, they conducted studies of acute HIV infection in MSM, looked at prevention and treatment of STIs, investigated predictors of HIV infection and the behavioral patterns of male sex workers who sell sex to other men, and evaluated the implementation of PrEP among MSM. “It is quite remarkable to have these cohorts in Africa, especially as Tanzania and Uganda have been much more aggressive toward MSM,” says Sanders.

Robert Bailey, an epidemiologist at the University of Illinois School of Public Health who helped design Kenya’s adult circumcision efforts and is now part of an effort to scale up PrEP use to 700 homosexual and bisexual men in Western Kenya says the country’s PrEP policy really comes down to human rights. “The Kenyan Constitution protects human rights,” says Bailey. “And a lot of the efforts by the Ministry of Health around PrEP for vulnerable people go under the umbrella that all Kenyans have universal human rights and providing services and access to health care is an essential part of that.”

Indeed, Kenya’s stated goal is to get to zero new HIV infections and do its part to help the United Nations reach its ambitious goal of ending AIDS by 2030.

But to that end, the country has a ways to go. While the latest incidence estimates from UNAIDS show that new HIV infections in Kenya dropped by 22 percent between 2012 and 2015, and the average HIV prevalence (5.9 percent) is half of what it was 20 years ago, there were still 78,000 new cases reported in 2015 and double-digit prevalence rates of 18 percent among MSM and IDUs, and 29 percent in sex workers. With 1.6 million people living with HIV, Kenya is still battling the spread of the virus.

PrEP’s implementation challenges

Given these figures, Kenya seems a logical place to implement PrEP. But even in other countries where HIV rates are highest in specific populations, the uptake of PrEP is happening somewhat slowly. In the US, despite strong marketing in at-risk communities, only approximately 136,000 individuals have started PrEP since Truvada received approval for prevention in 2012, according to pharmaceutical company Gilead, which makes Truvada (An Estimated 136,000 People Are on PrEP in the U.S., POZ, Aug. 18, 2017). Estimates suggest there are around 200,000 PrEP users worldwide. Without insurance, the cost for a year’s supply of PrEP in the US is around $8,000-$12,000, so price may be one issue impeding PrEP use, but other factors are less clear and harder to characterize. A recent article in The New York Times by an African-American gay man who lost both of his parents to AIDS, illustrates how challenging it can be convincing individuals to take PrEP. In this case, skepticism of doctors, monogamy, and concerns that the PrEP pill might “weaken his body,” convinced the writer to abandon PrEP after just one month (My Struggle to Take Anti-HIV Medicine, NY Times, Sept. 21, 2017).

In many settings it may be hard to convince healthy, uninfected individuals to swallow a pill every day, especially when it is an ARV ordinarily used to treat HIV infection. Numerous international clinical trials conducted in MSM, IDUs, high-risk heterosexual women, and serodiscordant couples have all found adherence to be the primary, and perhaps sole determinant, of PrEP efficacy. Yet there is no universal set of proven standards on how to convince people to start and faithfully use PrEP.

To make PrEP work in Kenya, the country will be seeking guidance from about a dozen ongoing demonstration projects and off-label studies, including five in Kenya, that have been examining the feasibility, cost-effectiveness, and acceptability of doling out daily oral PrEP to MSM, FSWs, and young women and adolescent girls (Preparing for PrEP, IAVI Report, Vol. 17, No. 3, 2013). Most of these projects are in the early stages or not yet started, but a few are already providing useful information. LVCT Health (formerly Liverpool VCT), a Kenyan non-profit that develops integrated HIV and reproductive health services for vulnerable populations, including MSM and sex workers, is leading a demonstration project that offers PrEP to at-risk individuals as part of a comprehensive HIV prevention package. They have noticed that support groups are an important resource in helping PrEP users remain adherent (Support Groups a Driver to PrEP Rollout in Kenya, PrEP Watch, June 2017). Groups of 10-15 people meet regularly to share their experiences and challenges with using PrEP, and while it’s hardly a 12-step program, people do, apparently, prod one another to stick to their daily pill.

Another demonstration project is Partners PrEP, an open label study of just over a thousand serodiscordant couples in Uganda and Kenya that has been building on the findings from the Partners PrEP trial, a randomized double-blind Phase III study of 4,500 heterosexual men and women that found tenofovir reduced the risk of infection by 62 percent, and daily Truvada reduced HIV infection risk by 73 percent (NEJM 367, 5, 399-410, 2012). The demonstration project found that a combination of PrEP and ARV therapy almost completely eliminated viral transmission in serodiscordant heterosexual couples. That data, presented two years ago at the Conference on Retroviruses and Opportunistic Infections, validated the idea of giving the HIV-negative partner PrEP as a “bridge” until or even after the infected partner begins full-scale ARV therapy.

KWTRP is also doing intensive outreach within MSM and FSW communities at their study sites in Mtwapa, Kilifi, and Malindi. Evanson Gichuru, a community liaison officer for IAVI’s KWTRP HIV project, says the centers sponsor weekly engagement meetings with a dozen randomly selected HIV-uninfected participants from their cohort. The meetings cover a combination of prevention strategies. PrEP discussions typically begin with an animated video clip and end with an open discussion about its usefulness and its potential side effects and adherence barriers, as well as ways to deal with those barriers. Since the introduction of PrEP in July 2017, they have mobilized 169 MSM and 50 FSWs who are eligible for PrEP.

From this group, Kimani Makobu, a physician at KWTRP, will be taking the work a step further by creating a cohort of 40 MSM and 40 FSWs to more closely monitor PrEP uptake and adherence. The group will be broken down into sub-categories, including gay and bisexual men as well as transgender women, because behavioral surveys suggest there are differences in risk-taking behavior in these groups and therefore each group will likely need individualized PrEP adherence support. Makobu, who is doing his PhD research under Sanders, says one thing he has learned from these focus groups is that some MSM suspect they will use condoms less.

“Incidence is highest in MSM and FSW so they would potentially be the biggest beneficiaries of PrEP,” says Makobu. “The caveat is that PrEP success is dependent upon users actually using it. If we are not able to motivate MSM and FSW to adhere to medication then the anticipated success may not be achieved.”

Despite what researchers are learning from demonstration projects, it is still an open question whether large numbers of at-risk individuals in uncontrolled settings will embrace PrEP, or shun it for any of a variety of reasons. Mombo Ngua (a.k.a. Mantully), a sexual minority activist affiliated with the Sex Workers Outreach Programme (SWOP) in Nairobi, who likes to end his emails with “If you hate gay marriages, blame the straight folks; they are the ones who keep having gay babies,” points out that there is a lot of misinformation, some perhaps deliberate, being spread by MSM about PrEP.

“There are people who are saying that PrEP does not work and they should use it without a condom and if they turn positive they should sue the government,” says Ngua. “They are telling people that it finishes sexual feeling and adds a tummy. They are saying if PrEP works, what’s the use of condoms?” Ngua, who has been working with the MSM community for over a decade is trying to dispel these myths, and he has a very good argument. He has been taking PrEP for two years. “I think more education and sensitization around PrEP is needed in the MSM community,” he says.

Finding ways to monitor PrEP users cost-effectively is also going to be a challenge in the long term, says Bailey. His research group in Kisumu, a county on the shores of Lake Victoria, is currently introducing PrEP to about 160 individuals from a long-standing cohort of 700 bisexual and homosexual men who they have been monitoring for years. The site hosts social events to engage the men—Monday movie night, coffee Wednesdays, fashion shows, and spiritual meetings—and uses peer educators to encourage adherence. The clinic also plans to monitor drug levels of PrEP participants to determine if it is being used consistently. But Bailey says the $50 per blood test will not be practical or cost-effective in a large-scale rollout, so the organizations charged with tracking these individuals will need to revert to behavioral methods of assessing adherence (for example, self-reporting or daily texts). As a result, “it’s going to be necessary to have some demonstration projects measure what the sensitivity and specificity of the behavioral methods of adherence are,” Bailey says.

Jhpiego, a global health non-profit and affiliate of Johns Hopkins University dedicated to improving the health of women and families in developing countries, is setting its sights on developing a model to scale-up PrEP in resource-strained countries through its Bridge To Scale project known as Jilinde. The Bill & Melinda Gates Foundation awarded Jhpiego $22.3 million over four years to reach 20,000 Kenyans most vulnerable to HIV infection, including adolescent girls and young women, FSWs, and MSM.

Daniel Were, oral PrEP director at Jhpiego-Kenya, says Jilinde, as part of a large technical working group spearheaded by the National AIDS and STI Control Programme (NASCOP), helped develop the framework for implementing oral daily PrEP, created training manuals and toolkits for providers and PrEP users, and will be conducting mathematical modeling in the third year of implementation to determine how much PrEP coverage is required to reduce infections in each risk group.

Jilinde, which means protect yourself in Swahili, already enrolled around 2,600 individuals at 10 different sites, but is encountering retention problems, possibly because people did not fully understand that the pills needed to be taken every day in order to work. “Many people are enrolling in the program but then quickly dropping and we’re trying to understand why this is happening,” says Were.

He says some reasons include an unwillingness to take a pill every day, or a preference for other HIV prevention options such as condoms. “Others enroll and drop out because of social stigma from their peers and surrounding community that labels them to be HIV positive because the medicine used for PrEP is similar to what is used for HIV treatment,” Were says.

So is Kenya ready for PrEP? Beyrer says Kenya has made tremendous strides but there are still challenges ahead. “Remember, when you look across the landscape things often look better in the larger urban areas. When you get out into more rural areas with smaller populations, you encounter much more traditional values and things can get really tough.”

Mary Rushton is a freelance writer based in Cambridge, Massachusetts.