Introduction Antiretroviral pre-exposure prophylaxis (PrEP) reduces the incidence of acquisition of human immunodeficiency virus type 1 (HIV-1) in men who have sex with men and is a promising approach for preventing HIV-1 in heterosexual populations. Methods We conducted a randomized, three-arm trial of oral antiretroviral PrEP among heterosexual couples from Kenya and Uganda in which one member was HIV-1 seronegative and the other HIV-1 seropositive. Seronegative partners were randomly assigned to once-daily tenofovir (TDF), combination emtricitabine/tenofovir (FTC/TDF), or matching placebo and followed monthly for up to 36 months. At enrollment, HIV-1 seropositive partners were not eligible for antiretroviral therapy under national guidelines. All couples received standard HIV-1 treatment and prevention services, including individual and couples risk-reduction counseling and condoms. Results 4758 couples were enrolled; for 62%, the HIV-1 seronegative partner was male. For HIV-1 seropositive participants, the median CD4 count was 495 cells/μL (interquartile range 375–662). Of 82 post-randomization HIV-1 infections, 17 were among those assigned TDF (incidence 0.65 per 100 person-years), 13 among those assigned FTC/TDF (incidence 0.50 per 100 person-years), and 52 among those assigned placebo (incidence 1.99 per 100 person-years), indicating a 67% relative reduction in HIV-1 incidence for TDF (95% CI 44 to 81, p<0.001) and 75% for FTC/TDF (95% CI 55 to 87, p<0.001). HIV-1 protective effects of FTC/TDF and TDF were not significantly different (p=0.23), and both study medications significantly reduced HIV-1 incidence in both men and women. The rate of serious medical events was similar across the study arms. Conclusions Oral TDF and FTC/TDF provided substantial protection against HIV-1 acquisition in heterosexual men and women, with comparable efficacy of TDF and FTC/TDF. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number NCT00557245)

Jessica Haberer and colleagues investigate the association between high adherence to antiretroviral pre-exposure prophylaxis and HIV transmission in a substudy of serodiscordant couples participating in a clinical trial. Please see later in the article for the Editors' Summary

No abstract

Objective Antiretroviral therapy (ART) significantly decreases HIV-associated morbidity, mortality, and HIV transmission through HIV viral load suppression. In high HIV prevalence settings, outreach strategies are needed to find asymptomatic HIV positive persons, link them to HIV care and ART, and achieve viral suppression. Methods We conducted a prospective intervention study in two rural communities in KwaZulu-Natal, South Africa, and Mbabara district, Uganda. The intervention included home HIV testing and counseling (HTC), point-of-care CD4 count testing for HIV positive persons, referral to care, and one month then quarterly lay counselor follow-up visits. The outcomes at 12 months were linkage to care, and ART initiation and viral suppression among HIV positive persons eligible for ART (CD4≤350 cells/μL). Findings 3,393 adults were tested for HIV (96% coverage), of whom 635 (19%) were HIV positive. At baseline, 36% of HIV positive persons were newly identified (64% were previously known to be HIV positive) and 40% were taking ART. By month 12, 619 (97%) of HIV positive persons visited an HIV clinic, and of 123 ART eligible participants, 94 (76%) initiated ART by 12 months. Of the 77 participants on ART by month 9, 59 (77%) achieved viral suppression by month 12. Among all HIV positive persons, the proportion with viral suppression (<1,000 copies/mL) increased from 50% to 65% (p=<0.001) at 12 months. Interpretation Community-based HTC in rural South Africa and Uganda achieved high testing coverage and linkage to care. Among those eligible for ART, a high proportion initiated ART and achieved viral suppression, indicating high adherence. Implementation of this HTC approach by existing community health workers in Africa should be evaluated to determine effectiveness and costs.

Background Community-based delivery of antiretroviral therapy (ART) for HIV, including ART initiation, clinical and laboratory monitoring, and refills, could reduce barriers to treatment and improve viral suppression, reducing the gap in access to care for individuals who have detectable HIV viral load, including men who are less likely than women to be virally suppressed. We aimed to test the effect of community-based ART delivery on viral suppression among people living with HIV not on ART. Methods We did a household-randomised, unblinded trial (DO ART) of delivery of ART in the community compared with the clinic in rural and peri-urban settings in KwaZulu-Natal, South Africa and the Sheema District, Uganda. After community-based HIV testing, people living with HIV were randomly assigned (1:1:1) with mobile phone software to community-based ART initiation with quarterly monitoring and ART refills through mobile vans; ART initiation at the clinic followed by mobile van monitoring and refills (hybrid approach); or standard clinic ART initiation and refills. The primary outcome was HIV viral suppression at 12 months. If the difference in viral suppression was not superior between study groups, an a-priori test for non-inferiority was done to test for a relative risk (RR) of more than 0•95. The cost per person virally suppressed was a co-primary outcome of the study. This study is registered with ClinicalTrials.gov, NCT02929992.

High-risk sexual or iatrogenic exposures may be important contemporary risk factors for HCV infection. The spontaneous viral clearance rate (18%) in this contemporary study was similar to that reported for past studies of transfusion-associated HCV infection. Women were more likely to clear acute HCV infection than men.

Clinical trials have ruled out a role of hydroxychloroquine in the treatment of COVID-19, but it has been hypothesized that hydroxychloroquine's activity against SARS-CoV-2 in the laboratory suggests a role in prevention. This randomized controlled trial tests hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.

Background We hypothesized that community-based HIV testing with counselor support and point-of-care CD4 count testing would increase uptake of antiretroviral therapy (ART) and male circumcision. Methods We conducted a randomized study of linkage strategies following community-based HIV testing in rural South Africa and Uganda. HIV-positive persons were randomized to 1) lay counselor follow-up home visits, lay counselor clinic linkage facilitation, or standard clinic referral; and then to either 2) point-of-care CD4 testing, or referral for CD4. HIV-negative uncircumcised men who could receive secure text messages were randomized to text message reminders, lay counselor visits, or referral. The primary outcomes were viral suppression at 9 months in HIV-positive persons and uptake of male circumcision by HIV-negative, uncircumcised men at 3 months. The study was registered at ClinicalTrials.gov (NCT02038582). Findings Between June 2013 and February 2015, 15,332 participants were tested; 1,325 HIV-positive persons and 750 HIV-negative uncircumcised men were randomized to linkage strategies. Among HIV-positive persons, overall clinic linkage was 93% (1,218/1,303) but ART initiation was only 37% (488/1,303). The proportion of persons who were virally suppressed ranged from 47%-52% (214/422 in the clinic referral arm, 219/419 in the clinic facilitation arm, and 202/431 in the lay counselor follow-up arm; p=0.668 and p=0.273, for the clinic facilitation and lay counselor follow-up arms, respectively, compared with clinic referral). There was no difference in viral suppression at 9 months by study arm. In the male circumcision clinic referral (standard of care) arm, 62/224 men (28%) were circumcised, compared to 137/284 (48%) in the text message reminder arm (RR=1.72, 95% CI 1.36-2.17) and 106/226 (47%) in the lay counselor follow-up arm (RR=1.67, 95% CI 1.29-2.14). Interpretation All the community-based strategies achieved very high rates of linkage of HIV positive persons to HIV clinics, approximately one-third of whom initiated ART, and approximately half were virally suppressed by 9 months. Clinic barriers to ART initiation must be addressed in future strategies to increase knowledge of HIV serostatus and linkage to HIV care. Uptake of male circumcision was almost two-fold higher among men who received text message reminders or lay counselor visits.