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.
Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely ...due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.
Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p<0.001). Median adherence was 99.1% (interquartile range IQR 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort.
The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.
BACKGROUND:A strategy of pre-exposure prophylaxis (PrEP) transitioning to treatment as prevention is highly efficacious and cost effective for prevention of HIV transmission within HIV serodiscordant ...couples. We assessed whether couples who adopted this strategy experienced changes in sexual behaviors after HIV-negative partners discontinued PrEP and transitioned to rely primarily on their partnerʼs adherence to antiretroviral therapy (ART) for prevention.
SETTING:Kenya and Uganda.
METHODS:Data are from the Partners Demonstration Project, a prospective, open-label evaluation of PrEP and ART use for HIV prevention. Using zero-inflated negative binomial models, we assessed changes in the level (ie, intercept) and trend over time (ie, slope) in total and condomless sex acts reported after PrEP discontinuation by HIV-negative partners. We conducted subgroup analyses based on HIV-negative partnersʼ age and sex.
RESULTS:We included 567 couples where the HIV-negative partner discontinued PrEP because of their partner with HIV using ART for ≥6 months. HIV-negative partners were women in 32.6% of couples and had a median age of 30 years. We observed no change in the level or trend over time in total sex acts level adjusted rate ratio (aRR) = 0.95, 95% confidence interval (CI)0.87 to 1.04; trend aRR = 1.00, 95% CI0.99 to 1.01 or condomless sex acts (level aRR = 0.97, 95% CI0.81 to 1.17; trend aRR = 1.00, 95% CI0.98 to 1.03) reported after PrEP discontinuation versus prediscontinuation. No significant changes in behaviors were observed in age and sex subgroups.
CONCLUSIONS:PrEP discontinuation seems to result in no significant changes in couplesʼ sexual behaviors. These data further support a strategy of time-limited PrEP use by serodiscordant couples.
Expedited partner treatment (EPT) is effective for preventing sexually transmitted infection recurrence, but concerns about intimate partner violence and missed opportunities for human immunology ...virus (HIV) testing have limited its use in African settings.
We conducted a pilot prospective evaluation of EPT among adolescent girls and young women (AGYW) accessing HIV preexposure prophylaxis in an implementation project in Kisumu, Kenya. Those with etiologic diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae were treated and given the option of delivering sexually transmitted infection medication and HIV self-test kits to their current sexual partner(s). At enrollment, we assessed their reasons for declining. Three months after they delivered medication and kits to the partner(s), we assessed their reasons for failing to deliver medication and kits to their partner and reported partner's reactions.
Between September 2018 and March 2020, 63 AGYW were enrolled. The majority (59/63 94%) accepted EPT, and 50 (79%) of 63 partner HIV self-testing (HIVST). Three quarters (46/59) of those accepting EPT returned for the assessment visit with 41 (89%) of 46 successfully delivering medication to 54 partners, of whom 49 (91%) used it. Seventy percent (35/50) who took partner HIVST kits returned for the assessment, with 80% (28/35) reporting providing kits to 40 partners, of whom 38 (95%) used it. Reported barriers to EPT and partner HIVST uptake among women who declined included anticipated fear that their partner could become angry or violent and loss of relationship.
Both EPT and partner HIVST were acceptable despite noted barriers among Kenyan AGYW with etiologic diagnosis of Chlamydia trachomatis/Neisseria gonorrhoeae and their partners.
PrEP use should be aligned with periods of risk for HIV acquisition. For HIV serodiscordant couples, PrEP can be used as a bridge until the partner living with HIV takes antiretroviral therapy (ART) ...long enough to achieve viral suppression (the "PrEP as a Bridge to ART" strategy). However, adherence to this strategy is unknown.
In a demonstration project in Kenya and Uganda, HIV-uninfected partners of serodiscordant couples were advised to take PrEP until the partner living with HIV took ART for ≥ 6 months. PrEP discontinuation was then recommended unless there were concerns about ART adherence, immediate fertility intentions, or outside partners with unknown HIV/ART status. Electronic adherence monitoring and socio-behavioral questionnaire data were used in logistic regression models to explore completion of this strategy and continuation of PrEP beyond recommendations to stop its use.
Among 833 serodiscordant couples, 436 (52%) HIV-uninfected partners completed ≥ 6 months of PrEP as a bridge to ART. Strategy completion was associated with older age (aOR per 5 years = 1.1; p = 0.008) and having fewer children (aOR = 0.9; p = 0.019). Of the 230 participants encouraged to stop PrEP according to strategy recommendations, 170 (74%) did so. PrEP continuation among the remaining 60 participants was associated with more education (aOR = 1.1; p = 0.029), a preference for PrEP over ART (aOR = 3.6; p = 0.026), comfort with managing their serodiscordant relationship (aOR = 0.6; p = 0.046), and believing PrEP makes sex safe (aOR = 0.5; p = 0.026).
Half of participants completed the PrEP as a bridge to ART strategy and the majority stopped PrEP as recommended. These findings suggest that targeting PrEP to periods of risk is a promising approach; however, tailoring counseling around aligning PrEP use and HIV risk will be important for optimal strategy implementation.
Summary Background Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to ...be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP. Methods We did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov , number NCT00557245. Findings 4410 (99·6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0·71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0·48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio HR 0·67, 95% CI 0·39–1·17; p=0·16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0·15, 95% CI 0·06–0·37; p<0·0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0·07, 0·02–0·23; p<0·0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups. Interpretation These results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women. Funding Bill & Melinda Gates Foundation and US National Institutes of Health.
Summary Background Most people infected with HIV-1 are dually infected with herpes simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it ...delays HIV-1 disease progression is unknown. We investigated the effect of aciclovir on HIV-1 progression. Methods In a trial with 14 sites in southern Africa and east Africa, 3381 heterosexual people who were dually infected with herpes simplex virus type 2 and HIV-1 were randomly assigned in a 1:1 ratio to aciclovir 400 mg orally twice daily or placebo, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per μL or higher and were not taking antiretroviral therapy. We used block randomisation, and patients and investigators were masked to treatment allocation. Effect of aciclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per μL, antiretroviral therapy initiation, or non-trauma related death. As an exploratory analysis, we assessed the endpoint of CD4 falling to <350 cells per μL. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov , number NCT00194519. Findings At enrolment, the median CD4 cell count was 462 cells per μL and median HIV-1 plasma RNA was 4·1 log10 copies per μL. Aciclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned aciclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio HR 0·84, 95% CI 0·71–0·98, p=0·03). In those with CD4 counts ≥350 cells per μL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per μL by 19% (0·81, 0·71–0·93, p=0·002) Interpretation The role of suppression of herpes simplex virus type 2 in reduction of HIV-1 disease progression before initiation of antiretroviral therapy warrants consideration. Funding Bill & Melinda Gates Foundation.
HIV risk perception may influence the use of HIV prevention interventions. Using data from HIV-negative adults enrolled in a study of pre-exposure prophylaxis (PrEP) and antiretroviral therapy for ...HIV-serodiscordant couples in Kenya and Uganda, we examined associations between: (1) condom use and risk perception and (2) risk perception and PrEP adherence. Two-thirds of HIV-negative partners reported condomless sex with their HIV-positive partner or another partner in the month prior to study enrollment. Compared to those who reported no condomless sex, participants who reported condomless sex during the month prior to study visit had fivefold higher odds of reporting “high risk” vs “no risk” perception (36.3 versus 10.9%: aOR 4.9, 95% CI 3.4–6.9). Reporting condomless sex in the most recent sex act was associated with increased odds of perceiving some HIV risk (aOR for high risk = 7.3, 95% CI 4.9–10.8; aOR for moderate risk = 4.8, 95% CI 3.5–6.7; aOR for low risk = 3.5, 95% CI 2.7–4.6). We found no significant association between risk perception and PrEP adherence. Sexual behavior aligned with perceived HIV risk, which can facilitate an HIV-negative individual’s decisions about PrEP use.
Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study ...is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.
HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.
From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners IQR (28-40) and (26-39) respectively. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0) and recent knowledge of their serodiscordant status median 0.4 years (IQR 0.1-2.0). During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10) copies/mL (IQR 3.31-4.53) and median CD4 count was 496 cells/µL (IQR 375-662); the majority (64%) had WHO stage 1 HIV-1 disease.
Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245).
: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk. Demonstration projects ...conducted in diverse settings worldwide illustrate practical examples of how PrEP can be delivered. This manuscript presents estimates of effectiveness and patterns of PrEP use within a two-year demonstration project of PrEP for HIV-negative members of heterosexual HIV serodiscordant couples in East Africa.
: The PrEP delivery model integrated PrEP into HIV treatment services, prioritizing PrEP use for HIV-negative partners within serodiscordant couples before and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART). We measured PrEP uptake through pharmacy records and adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial.
: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP. Ninety-seven percent of HIV-negative partners initiated PrEP. Objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected. Four incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.
: PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV. Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.
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