PrEP for Africa: What we have learnt and what is needed to move to program implementation

Health systems considerations

Public health policy guidance in Kenya, similar to other countries in Africa, often faces tensions between the vertical systems that have single-purpose machinery in facilities, human resources [11], management, information, logistics and supplies and horizontal systems that deliver integrated services. Implementation of PrEP should take cognizance and test both systems in order to provide guidance for practical application. The issue of cost is pertinent, as consideration is needed for additional resources in terms of personnel, procurement and supplies, and monitoring and evaluation, as well as how PrEP interfaces with other competing local health problems.

Delivery avenues

There are lessons to be learnt from the initiation of ART in Africa, where delivery started with private provider prescription, which built demand in public sector and wide scale access. Delivery venues should also reflect the needs of vulnerable populations, which may be vastly different for MSM, FSW, young women in high prevalence settings, fisher folk and other mobile populations. Avenues for delivery for young women, assisted with tools to identify those at substantial risk, should consider family planning and maternal child health facilities as options for delivery, as well as innovative approaches such as youth services and HIV testing venues. The adolescent population has less well-defined delivery avenues and few demonstration projects to inform delivery strategies. As often stated by civil society ‘nothing for us without us’ we should engage populations to inform strategies on effective delivery of HIV PrEP. Delivery to MSM populations in sub-Saharan Africa will require special considerations, given heavily stigmatized social and political environment. Outside of South Africa, there is only one MSM demonstration project in Kenya, perhaps due to these challenges. Yet, MSM contribute significantly to the epidemic in every country, including as a bridging group to other populations (for example, men who have sex with men and with women).

PrEP use is not life-long

Young women, MSM, sex workers and HIV serodiscordant couples are not at uniform risk throughout their lives, and thus PrEP need not be life-long. Vulnerability to HIV is usually time limited to a ‘season in life’ where economic dependency, self-determination and decision-making are limited by social-economic environment. [17–22] Some work has been done to evaluate HIV risk and predict incidence with development of an HIV ‘risk scores’ for HIV serodiscordant couples [23] that could implemented in clinical evaluation. PrEP programs need to develop tools to determine individuals’ ‘season of risk’ and provide PrEP alongside other appropriate interventions for a limited duration. Time limited use of PrEP, as a product to be used during the ‘seasons of high risk’ is an important message for both the health provider and end user and has a strong impact on acceptability of product, and separates use of PrEP from ART for treatment.

Addressing Providers, Policy Makers and End Users Concerns

Concerns that PrEP will increase risk of resistance to antiretroviral treatment medications, reduce condom use and compete with resources to expand access to HIV treatment have been raised, although open label studies and demonstration projects provide evidence to the contrary. Interviews with female sex workers in Kenya cited the blue color of the Truvada® pill being similar to local mood altering drug and a possible barrier to adherence (unpublished LVCT-Health). Communication strategies that target potential users providing current and correct information regarding PrEP benefits and risks should be part of implementation. Social marketing strategies need to work with policy makers and target population, influence perceptions that oppose PrEP as a potential inhibitor to expanding antiretroviral therapy for treatment and mobilize communities to encourage those at HIV risk to access HIV PrEP.

Safety and laboratory assessment

The frequency of creatinine testing and need for hepatitis B screening for programs may limit access to PrEP especially in areas in sub-Sahara Africa. Recently released WHO guidelines for ART and PrEP are permissive to limited or no testing, so as not to make testing a barrier to PrEP. [10] The PROUD study initiated PrEP without a screening visit and reviewed renal safety data with no safety breech after one month. [8] There is a high safety threshold for disease prevention drugs for use by healthy populations such as PrEP. Health care providers’ and communities’ concerns about safety can impede uptake. Across all studies, PrEP has demonstrated high tolerability and low toxicity profile. Questions of rare renal toxicity, reduction in bone mineral density, and safety in persons with chronic hepatitis B require research in parallel to delivery. [24–26] Similarly, additional research is needed to define a minimum safety package for PrEP, analogous to the scale back of treatment safety monitoring.

Adherence

A range of novel treatment adherence strategies have been employed globally and particularly in sub-Saharan Africa with varying degrees of success. [27] Although treatment offers lessons, it is different from PrEP, which is for a shorter duration but in a healthy population. The majority of countries in Africa have a strong community strategy for delivery of health services, including for HIV treatment, and community health workers have been an important partner in supporting adherence and retention. A similar strategy should be considered for supporting PrEP adherence and retention.

Learning from PrEP demonstration projects

Adherence has been high in demonstration projects, as reflected in >80% effectiveness [5,8]. Confirmation from clinical trials that PrEP works when taken has greatly influenced uptake and adherence. Clinic visits for participants in the majority of demonstration projects have been quarterly with less follow up for retention than in the randomized clinical trials.

In the South Africa, ADAPT study (HPTN 067) site has demonstrated an adherence of 79% among young women confirming that young women in Africa are able and willing to use PrEP. [28] Similar high adherence and effectiveness with almost near elimination of HIV among HIV serodiscordant couples was demonstrated in the Partners Demonstration Project (Kenya and Uganda) with an effectiveness of 96% (95% CI 81–99%). [5] Interestingly in both Partners Demonstration Project and the PROUD study [5,8], there was no breakthrough infection among participants using PrEP as confirmed by investigators. The majority of PrEP demonstration projects (Table 1) in Africa will have results on feasibility and acceptance by 2016. However, there are very few studies among MSM, which may be related to a hostile political and social environment that make it more difficult to provide health interventions to this community, and too few studies among young women at risk. Projects that bridge demonstration to true implementation are needed, and step-wise advancement needs to accelerate, in multiple populations and multiple countries.

Addressing individual barriers to PrEP uptake

Qualitative studies in Kenya and Nigeria have identified population level stigma as a key barrier to PrEP uptake [29]. Similarly, interviews with women enrolled in the VOICE and FEM-PrEP studies reported stigma to use of an antiretroviral treatment, lack of risk perception, uncertainty about efficacy and lack of partner support as barriers to product use. [30,31] Interviews with policy makers and community leaders reported lack of access to services, compounded by fears, lack of awareness and misinformation as barriers to PrEP uptake. Social marketing campaigns will be required to reduce community and individual level stigma.

Prioritizing Couples

In Nigeria stakeholders [29] proposed HIV serodiscordant couples as the appropriate population for initiating demonstration projects. The respondents cited that condoms are a barrier to conception and PrEP would bring hope, assist mutual adherence resolve the discordance dilemma. Data from the Partners PrEP Study and Partners Demonstration Project supported these findings, with high adherence when PrEP was provided as a bridge to ART. [5] HIV serodiscordant couples in Uganda felt that PrEP helped them resolve ‘discordance dilemma’ safeguard the health of the HIV-negative partner and allow them to retain the relationship. [32] Natural conception for HIV serodiscordant couples carries substantial risk of HIV transmission, however, in qualitative interviews of HIV-serodiscordant couples conception desires outstrip fear of HIV acquisition. [33] PrEP provides an option for couples to achieve fertility desires with reduced risk of HIV-transmission. We have substantial evidence to commence PrEP delivery to HIV-serodiscordant couples. Politically, this population may de-stigmatize PrEP and allow for informing PrEP delivery models for MSM and young women in Africa, where there may be greater reticence and fewer delivery models.

Targeting those at greatest risk for HIV infection

For PrEP implementation to be cost effective, it should be for a limited duration during the ‘period of risk’ and targeted to those at substantial risk for HIV infection. Among HIV serodiscordant couples, the number needed to treat (NNT) to avert one HIV infection was less than 30, when targeted to couples with an HIV incidence of ≥5/100 person years, similarly among MSM in the iPrEx study [34] [23,35]

The HIV epidemic in Africa is complex, and outside of ‘key populations’ fisher folk [21,36], and slum dwellers [21,22] are examples of populations at substantial risk HIV infection [19]. In addition young women [37,38], pregnant and post-partum women are at high risk for infection, more so those who live in high prevalence geographic locations [39,40]. In implementing PrEP, the approach of targeting can be stigmatizing and become a barrier to uptake. PrEP should not be branded only for ‘promiscuous’ individuals, which may limit access and backfire by limiting demand. We need practical strategies for reaching those who need PrEP, including but not limited to self-referrals. Defining a marketing approach, using epidemiologic data and offering an appropriate, convenient safe avenue for delivery may get to the people at greatest risk without introducing stigma.

PrEP uptake is highest among those at high risk for HIV infection

The majority of MSM PrEP studies have been done outside of Africa, however, they have shown substantial PrEP uptake among those with a history high risk sexual behaviour. [41] In the Partners PrEP study, tenofovir ≤40 ng/mL (indicating low adherence) was associated with periods when participants reported no sex with their HIV infected partner compared to periods of unprotected sex. [42] In a program setting risk assessment should be part of evaluation prior to initiation of PrEP. During follow up risk assessments should be done to identify periods of high risk when adherence is critical [27].

Risk compensation

Often voiced is the concern that PrEP would reduce condom use and increase risks for other STIs. PrEP clinical trial data do not suggest substantial risk compensation, and instead suggested reduced risk over time, perhaps reflecting synergies with counseling and periodic HIV testing. [43,44] What is most compelling is the evidence that PrEP uptake and adherence in demonstration projects seems to map those individuals with greatest risk-i.e., users respond to their own risk by initiating PrEP (rather than PrEP leading to risk).

Summary

Policy guidance is essential to PrEP Implementation through programs in Africa. To initiate the process of implementation, policymakers need to be convinced that HIV PrEP will be cost effective, affordable and deliverable through an integrated horizontal health system. Communities’ and PrEP users’ perceptions of PrEP will also determine uptake, and a strong advocacy strategy is needed to create awareness and safeguard against stigma towards users and PrEP itself. PrEP holds substantial potential for Africa – actions to deliver PrEP are needed now to assess whether we can realize that potential.