Following recommendations by the World Health Organization in 2015, and key clinical trials, countries in sub-Saharan Africa, the region with the highest burden of human immunodeficiency virus (HIV), ...developed policies that incorporate pre-exposure prophylaxis (PrEP) into national HIV-prevention strategies. By the end of 2019, more than one third of people receiving PrEP globally were in Africa. Crucial understandings gained from early rollout among at-risk populations, such as HIV-serodiscordant couples, adolescent girls and young women, female sex workers, and men who have sex with men, include the importance of strategies for maintaining persistent adherence to PrEP and novel approaches to making PrEP services accessible, simplified and efficient. This Perspective will discuss the current status of these programs and how to further widen their implementation.
Young women account for a disproportionate fraction of new HIV infections in Africa and are a priority population for HIV prevention, including implementation of preexposure prophylaxis (PrEP). The ...overarching goal of this project was to demonstrate the feasibility of integrating PrEP delivery within routine family planning (FP) clinics to serve as a platform to efficiently reach at-risk adolescent girls and young women (AGYW) for PrEP in HIV high-burden settings.
The PrEP Implementation in Young Women and Adolescents (PrIYA) program is a real-world implementation program to demonstrate integration of PrEP delivery for at-risk AGYW in FP clinics in Kisumu, Kenya. Between November 2017 and June 2018, women aged 15 to 45 from the general population seeking FP services at 8 public health clinics were universally screened for HIV behavioral risk factors and offered PrEP following national PrEP guidelines. We evaluated PrEP uptake and continuation, and robust Poisson regression methods were used to identify correlates of uptake and early continuation of PrEP, with age included as a one-knot linear spline. Overall, 1,271 HIV-uninfected women accessing routine FP clinics were screened for PrEP; the median age was 25 years (interquartile range IQR: 22-29), 627 (49%) were <24 years old, 1,026 (82%) were married, more than one-third (34%) had partners of unknown HIV status, and the vast majority (n = 1,200 94%) reported recent condom-less sex. Of 1,271 women screened, 278 (22%) initiated PrEP, and 114 (41%) returned for at least one refill visit after initiation. PrEP uptake was independently associated with reported male-partner HIV status (HIV-positive 94%, unknown 35%, HIV-negative 8%; p < 0.001) and marital status (28% unmarried versus married 21%; p = 0.04), and a higher proportion of women ≥24 years (26%; 191/740) initiated PrEP compared to 16% (87/531) of young women <24 years (p < 0.001). There was a moderate and statistically non-significant unadjusted increase in PrEP uptake among women using oral contraception pills (OCPs) compared to women using injectable or long-acting reversible contraception methods (OCP 28% versus injectable/implants/intrauterine devices IUDs 18%; p = 0.06). Among women with at least one post-PrEP initiation follow-up visit (n = 278), no HIV infection was documented during the project period. Overall, continuation of PrEP use at 1, 3, and 6 months post initiation was 41%, 24%, and 15%, respectively. The likelihood for early continuation of PrEP use (i.e., return for at least one PrEP refill within 45 days post initiation) was strongly associated with reported male-partner HIV status (HIV-positive 67%, -negative 39%, unknown 31%; overall effect p = 0.001), and a higher proportion of women ≥24 years old continued PrEP at 1 month compared with young women <24 years old (47% versus 29%; p = 0.002). For women ≥24 years old, the likelihood to continue PrEP use at 1 month post initiation increased by 3% for each additional year of a woman's age (adjusted prevalence ratio PR: 1.03; 95% confidence interval CI: 1.01-1.05; p = 0.01). In contrast, for women <24 years old, the likelihood of continuing PrEP for each additional year of a woman's age was high in magnitude (approximately 6%) but statistically non-significant (adjusted PR: 1.06; 95% CI: 0.97-1.16; p = 0.18). Frequently reported reasons for discontinuing PrEP were low perceived risk of HIV (25%), knowledge that partner was HIV negative (24%), experiencing side effects (20%), and pill burden (17%). Study limitations include lack of qualitative work to provide insights into women's decision-making on PrEP uptake and continuation, the small number of measured covariates imposed by the program data, and a nonrandomized design limiting definitive ascertainment of the robustness of a PrEP-dedicated nurse-led implementation strategy.
In this real-world PrEP implementation program in Kenya, integration of universal screening and counseling for PrEP in FP clinics was feasible, making this platform a potential "one-stop" location for FP and PrEP. There was a high drop-off in PrEP continuation, but a subset of women continued PrEP use at least through 1 month, possibly indicating further reflection or decision-making on PrEP use. Greater efforts to support PrEP normalization and persistence for African women are needed to help women navigate their decisions about HIV prevention preferences as their reproductive goals and HIV vulnerability evolve.
Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence ...support strategies for African AGYW were studied in an implementation study. HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV-negative women ages 16-25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP greater than or equal to700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio OR of 0.92; 95% confidence interval CI 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted. In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population.
Successful scale-up of PrEP for HIV prevention in African adolescent girls and young women (AGYW) requires integration of PrEP into young women's everyday lives. We conducted interviews and focus ...group discussions with 137 AGYW PrEP users aged 16-25 from South Africa and Kenya. Individual and relational enablers and disablers were explored at key moments during their PrEP-user journey from awareness, initiation and early use through persistence, including PrEP pauses, restarts, and discontinuation. PrEP uptake was facilitated when offered as part of an integrated sexual reproductive health service, but hampered by low awareness, stigma and misconceptions about PrEP in the community. Daily pill-taking was challenging for AGYW due to individual, relational and structural factors and PrEP interruptions (intended or unintended) were described as part of AGYW's PrEP-user journey. Disclosure, social support, adolescent-friendly health counseling, and convenient access to PrEP were reported as key enablers for PrEP persistence.
Summary Background High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We ...aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Methods Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per μL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants. Findings 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161–265) cells per μL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0·37 (95% CI 0·09–2·04) per 100 person-years in those who had initiated treatment and 2·24 (1·84–2·72) per 100 person-years in those who had not—a 92% reduction (adjusted incidence rate ratio 0·08, 95% CI 0·00–0·57, p=0·004). In participants not on ART, the highest HIV-1 transmission rate (8·79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per μL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per μL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. Interpretation Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission. Funding Bill & Melinda Gates Foundation; US National Institutes of Health.
BACKGROUND:Oral pre-exposure prophylaxis (PrEP) is effective for HIV prevention, and PrEP delivery studies are investigating ways to deliver PrEP with high adherence. However, in many settings with ...high HIV burden, intimate partner violence (IPV) is reported often and could be a barrier to the effective PrEP use. We examined the association between IPV and interruptions in PrEP use.
METHODS:We analyzed data from 1013 serodiscordant heterosexual couples enrolled in a large PrEP demonstration project in Kenya and Uganda, the Partners Demonstration Project. At quarterly study visits, HIV-negative participants receiving PrEP were asked about interruptions in their PrEP use and experiences with IPV. The association between IPV and PrEP interruptions was analyzed using multivariable generalized estimating equations.
RESULTS:At baseline and follow-up, there were 53 visits with reports of abuse by 49 HIV-negative partners, including physical, economic, and verbal IPV. Interruptions in PrEP use were reported at 328 visits (7.1% of all visits) by 249 people. The median length of PrEP interruption was 28 days (interquartile range7–45). The frequency of PrEP interruptions among those reporting IPV was 23.8% and those without IPV was 6.9%. PrEP interruption was significantly associated with IPV after adjustment for age and frequency of sexual intercourse (adjusted odds ratio = 2.6, 95% confidence interval1.2 to 6.0).
CONCLUSIONS:IPV was more likely to be reported at visits when PrEP interruptions were also reported, which may have implications for sustained adherence to PrEP. Within PrEP delivery programs, there may be opportunities to assess individual safety and well-being to bolster adherence.
Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce ...the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.
Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.
Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.
Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital ...tract of HIV-1-infected women. However, whether BV, which is present in up to half of African HIV-1-infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1-seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1-seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7-10 and 0-3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1-infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1-infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74-7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37-7.33).
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥ 250 cells/mm³ and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1-infected women could mitigate female-to-male HIV-1 transmission.
ClinicalTrials.com NCT00194519.
PURPOSE OF REVIEWTopical tenofovir gel and oral tenofovir and emtricitabine–tenofovir FTC/tenofovir disoproxyl fumarate (TDF) have been demonstrated to have efficacy in preventing HIV-1 in some ...populations. Preexposure prophylaxis (PrEP) trials and future directions are summarized.
RECENT FINDINGSPericoital use of 1% tenofovir gel in the CAPRISA 004 study reduced HIV-1 acquisition by 39% and herpes simplex virus-2 acquisition by 51%. Daily oral FTC/TDF demonstrated 44% reduction in HIV-1 acquisition among MSM in the iPrEx study (Pre-Exposure Prophylaxis Initiative). Both studies showed higher efficacy among those with higher adherence. Efficacy of daily oral TDF and FTC/TDF was 66 and 73%, respectively, among HIV-1-uninfected partners in an HIV-1 serodiscordant partnership in the Partners PrEP Study. Efficacy of daily oral FTC/TDF was 66% in young heterosexuals in Botswana in the TDF2 trial. The FEM-PrEP and VOICE (Vaginal and Oral Interventions to Control the Epidemic) studies in African women found no efficacy with oral FTC/TDF and TDF, respectively. Safety and tolerability were excellent and limited resistance was observed in seroconverters.
SUMMARYTopical tenofovir gel showed efficacy in African women and daily oral TDF and FTC/TDF were efficacious in MSM, and African HIV-1 serodiscordant couples and young heterosexuals. The reasons for lack of efficacy of oral FTC/TDF and TDF in two studies in African women are being investigated. Longer-acting formulations, invtravaginal rings, and new candidate antiretrovirals are being evaluated for pre-exposure prophylaxis (PrEP).
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