Ting Hong

Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples

In a prospective study, Craig Cohen and colleagues investigate the association between bacterial vaginosis and the risk of female-to-male HIV-1 transmission.

Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial.

IMPORTANCE Antiretroviral preexposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF) and combination emtricitabine/tenofovir disoproxil fumarate (FTC+TDF), is efficacious for prevention of human immunodeficiency virus (HIV) acquisition. PrEP could reduce periconception HIV risk, but the effect on pregnancy outcomes is not well defined. OBJECTIVE To assess pregnancy incidence and outcomes among women using PrEP during the periconception period. DESIGN, SETTING, AND PARTICIPANTS Randomized trial among 1785 HIV-serodiscordant heterosexual couples (the Partners PrEP Study) in which the female partner was HIV uninfected that demonstrated that PrEP was efficacious for HIV prevention, conducted between July 2008 and June 2013 at 9 sites in Kenya and Uganda. INTERVENTIONS Daily oral TDF (n = 598), combination FTC+TDF (n = 566), or placebo (n = 621) through July 2011, when PrEP demonstrated efficacy for HIV prevention. Thereafter, participants continued receiving active PrEP without placebo. Pregnancy testing occurred monthly and study medication was discontinued when pregnancy was detected. MAIN OUTCOMES AND MEASURES Pregnancy incidence, birth outcomes (live births, pregnancy loss, preterm birth, congenital anomalies), and infant growth. RESULTS A total of 431 pregnancies occurred. Pregnancy incidence was 10.0 per 100 person-years among women assigned placebo, 11.9 among those assigned TDF (incidence difference, 1.9; 95% CI, -1.1 to 4.9 [P = .22 vs placebo]), and 8.8 among those assigned FTC+TDF (incidence difference, -1.3; 95% CI, -4.1 to 1.5 [P = .39 vs placebo]). Before discontinuation of the placebo treatment group in July 2011, the occurrence of pregnancy loss (96 of 288 pregnancies) was 42.5% for women receiving FTC+TDF compared with 32.3% for those receiving placebo (difference for FTC+TDF vs placebo, 10.2%; 95% CI, -5.3% to 25.7%; P = .16) and was 27.7% for those receiving TDF alone (difference vs placebo, -4.6%; 95% CI, -18.1% to 8.9%; P = .46). After July 2011, the frequency of pregnancy loss (52 of 143 pregnancies) was 37.5% for FTC+TDF and 36.7% for TDF alone (difference, 0.8%; 95% CI, -16.8% to 18.5%; P = .92). Occurrence of preterm birth, congenital anomalies, and growth throughout the first year of life did not differ significantly for infants born to women who received PrEP vs placebo. CONCLUSIONS AND RELEVANCE Among HIV-serodiscordant heterosexual African couples, differences in pregnancy incidence, birth outcomes, and infant growth were not statistically different for women receiving PrEP with TDF alone or combination FTC+TDF compared with placebo at conception. Given that PrEP was discontinued when pregnancy was detected and that CIs for the birth outcomes were wide, definitive statements about the safety of PrEP in the periconception period cannot be made. These results should be discussed with HIV-uninfected women receiving PrEP who are considering becoming pregnant. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00557245.

Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial.

BACKGROUND Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC-TDF) reduces the risk for HIV-1 acquisition. Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2). OBJECTIVE To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition. DESIGN Subgroup analysis of data from a randomized, placebo-controlled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245). SETTING Multiple sites in Kenya and Uganda. PARTICIPANTS Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1-infected partner. INTERVENTION Once-daily oral tenofovir disoproxil fumarate (TDF), alone or combined with emtricitabine (FTC-TDF), compared with placebo. MEASUREMENTS HSV-2 seroconversion. RESULTS A total of 131 participants seroconverted to HSV-2 (79 of 1041 assigned to tenofovir or FTC-TDF PrEP [HSV-2 incidence, 5.6 per 100 person-years] and 52 of 481 assigned to placebo [HSV-2 incidence, 7.7 per 100 person-years]). The hazard ratio (HR) for HSV-2 acquisition with daily oral PrEP was 0.70 (95% CI, 0.49 to 0.99; P = 0.047) compared with placebo, and the absolute risk reduction was 2.1 per 100 person-years. Among the 1044 participants with HSV-2-infected partners, the HR for PrEP was 0.67 (CI, 0.46 to 0.98; P = 0.038) compared with placebo, and the absolute risk reduction was 3.1 per 100 person-years. LIMITATION Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available. CONCLUSION Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women. Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP. PRIMARY FUNDING SOURCE Bill & Melinda Gates Foundation.

Depression and Anxiety as Risk Factors for Delayed Care-Seeking Behavior in Human Immunodeficiency Virus–Infected Individuals in South Africa

Background Facility- and community-based efforts to improve human immunodeficiency virus (HIV) testing in sub-Saharan Africa may benefit from understanding how mental health influences HIV care-seeking behavior. Methods We conducted a study among adults presenting for HIV testing in the Umlazi township of South Africa. Prior to testing, we measured depression using the 9-item Patient Health Questionnaire and anxiety using the 7-item Generalized Anxiety Disorder scale. We categorized patients as delayed presenters (presenting to clinic >3 months after first HIV-positive test), late testers (presenting within 3 months of diagnosis with a CD4 count ≤200 cells per µL), or neither. We used multinomial logistic regression adjusting for sociodemographic and behavioral characteristics to determine the effects of depression and anxiety on HIV care-seeking behavior. Results Among 1482 HIV-infected adults, 59% were female and mean age was 33 years. The prevalence of depression in the cohort was 33% and anxiety was 9%. In adjusted models, mild to moderate depression was not associated with delayed presentation or late testing. HIV-infected adults with severe depression had 3.6 greater odds (95% confidence interval [CI], 1.2-10.2) of delayed presentation and 2.2 greater odds (95% CI, 1.01-4.8) of late testing compared with those without depression. Individuals with generalized anxiety had 2.3 greater odds (95% CI, 1.3-4.2) of delayed presentation compared with those without anxiety. Conclusions Severe depression was associated with delayed presentation and late testing, while anxiety was associated only with delayed presentation. Screening for mental health services may improve antiretroviral therapy initiation and linkage to care following HIV testing.

Herpes simplex virus type 2 acquisition among HIV-1-infected adults treated with Tenofovir disoproxyl fumarate as part of combination antiretroviral therapy: Results from the ACTG A5175 PEARLS study

Objective Tenofovir disoproxyl fumarate (TDF) disoproxyl fumarate (TDF) has in vitro activity against herpes simplex virus type 2 (HSV-2) and reduced HSV-2 acquisition as preexposure prophylaxis. Whether TDF-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Design Secondary analysis of AIDS Clinical Trials Group A5175, a randomized, open-label study of 3 ART regimens among 1571 participants. Methods HSV-2 serostatus was assessed at baseline, at study exit, and before a change in ART regimen. Results Of 365 HSV-2-seronegative persons, 68 acquired HSV-2, with 24 receiving TDF-containing ART and 44 receiving ART without TDF (HSV-2 seroconversion incidence, 6.42 and 6.63 cases/100 person-years, respectively; hazard ratio, 0.89; 95% confidence interval, .55-1.44). Conclusions HSV-2 acquisition was not reduced in HIV-infected, HSV-2-uninfected persons during TDF-containing ART.Objective Tenofovir has in vitro activity against HSV-2 and reduced HSV-2 acquisition as pre-exposure prophylaxis. Whether tenofovir-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Design Secondary analysis of ACTG A5175, a randomized, open-label study of three ART regimens among 1,571 participants. Methods HSV-2 serostatus was assessed at baseline, exit and prior to ART change. Results Of 365 HSV-2 seronegative persons, 68 acquired HSV-2 with 24 on tenofovir-containing ART and 44 on ART without tenofovir (HSV-2 incidence 6.42 and 6.63/100 person-years, respectively; Hazard Ratio 0.89; 95% Confidence Interval 0.55-1.44). Conclusions HSV-2 acquisition was not reduced in HIV-infected, HSV-2 uninfected persons on tenofovir-containing ART.

Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

P3.226 Pre-Exposure Prophylaxis (PrEP) is Estimated to Be a Cost-Effective Addition to Antiretroviral Therapy (ART) For HIV Prevention in a Generalised Epidemic Setting

Background In KwaZulu-Natal, South Africa, young women face an extraordinarily high risk for HIV acquisition, with annual incidence estimates of 6%. ART-based strategies for HIV prevention have the potential to significantly decrease HIV incidence, but the impact of PrEP in addition to ART scale-up is undefined. Modeling studies suggest that PrEP targeted to highest-risk groups could maximise benefits and contain costs. Methods We developed a deterministic transmission model of HIV that stratifies the population by age, sexual activity, and includes HIV infection stage. The model was parameterized using data from community-based HIV counselling and testing studies in KwaZulu-Natal and validated using independent HIV prevalence and incidence estimates. We estimated the effectiveness and cost-effectiveness of a ‘test and treat’ scenario, targeted PrEP by age and sexual activity, and general PrEP provision. Each scenario was in addition to anticipated baseline ART scale-up for CD4≤ 350 from 35% in 2013, as observed in KwaZulu-Natal, to 60% in 2018 (following national guidelines). We assumed PrEP efficacy of 70%. Results ‘Test and treat’ (ART for 80% of all HIV-positive persons) reduced HIV incidence by 58% and averted 25% of cumulative infections by 2025, at an additional

Correlation Between Pill Counts and Biologic Effects in an HIV-1 Prevention Clinical Trial: Implications for Measuring Adherence

39,900 per infection averted compared to baseline ART scale-up. PrEP targeted to 60% of 20–29-year-olds, in addition to baseline ART scale-up, reduced incidence by 42% and averted 22% of infections at an additional

C-reactive protein as a screening test for HIV-associated pulmonary tuberculosis prior to antiretroviral therapy in South Africa

22,500 per infection averted, whereas PrEP targeted to 80% of high-risk individuals reduced incidence by 33% and averted 13% of infections at an additional

Pregnancy outcomes and infant growth among babies with in-utero exposure to tenofovir-based preexposure prophylaxis for HIV prevention

7,400 per infection averted. PrEP coverage of 20% of the general population reduced incidence by 37% and incident infections by 18%, at an additional