SummaryBackgroundThe interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes.MethodsWe did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I2 statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546).FindingsWe identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70–0·99; I2=51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40–1·06; I2=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40–0·87; I2=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54–0·75; I2=18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30–1·82; I2=0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18–0·87, I2=33%).InterpretationEarly ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect.FundingUK Medical Research Council.

Background Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression. Methods Between January 2004 to August 2008, 1,142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA PCR at 4-6 weeks) were assessed with multivariate logistic regression. Results Mean age was 30.2 years (SD=5.0) and median baseline CD4 count was 161 cells/mm3 (SD=84.3). HAART duration at time of delivery was a mean 10.7 weeks (SD=7.4) for the 85% of women who initiated treatment during pregnancy and 93.4 weeks (SD=37.7) for those who became pregnant on HAART. Overall MTCT rate was 4.9% (43/874), with no differences detected between HAART regimens. MTCT rates were lower in women who became pregnant on HAART than those initiating HAART during pregnancy (0.7% versus 5.7%; p=0.01). In the latter group, each additional week of treatment reduced odds of transmission by 8% (95% CI: 0.87-0.99, p=0.02). Conclusion Late initiation of HAART is associated with increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV-infected women.

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 HIV self-testing increases testing uptake in sub-Saharan Africa but scale-up is challenging because of resource constraints. We evaluated an HIV self-testing intervention integrated into high-burden outpatient departments in Malawi.Methods In this cluster-randomised trial, we recruited participants aged 15 years or older from 15 outpatient departments at high-burden health facilities (including health centres, mission hospitals, and district hospitals) in central and southern Malawi. The trial was clustered at the health facility level. We used constrained randomisation to allocate each cluster (1:1:1) to one of the following groups: standard provider-initiated testing and counselling with no intervention (provider offered during consultations), optimised provider-initiated testing and counselling (with additional provider training and morning HIV testing), and facility-based HIV self-testing (Oraquick HIV self-test, group demonstration and distribution, and private spaces for interpretation and counselling). The primary outcome was the proportion of outpatients tested for HIV on the day of enrolment, measured through exit surveys with a sample of outpatients. Analyses were on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03271307, and Pan African Clinical Trials, PACTR201711002697316.

BackgroundUse of highly active antiretroviral therapy (HAART), a triple-drug combination, in HIV-infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development.MethodsOur objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5 kg) and preterm birth rates (<37 weeks) were compared between those exposed and unexposed to HAART during pregnancy. Effects of different HAART regimen and duration were assessed.ResultsAmong HAART-unexposed infants, 27% (60/224) were low birth weight compared with 23% (90/388) of early HAART-exposed (exposed <28 weeks gestation) and 19% (76/407) of late HAART-exposed (exposed ≥28 weeks) infants (p = 0.05). In the early HAART group, a higher CD4 cell count was protective against low birth weight (AOR 0.57 per 50 cells/mm3 increase, 95% CI 0.45-0.71, p < 0.001) and preterm birth (AOR 0.68 per 50 cells/mm3 increase, 95% CI 0.55-0.85, p = 0.001). HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001), with early nevirapine and efavirenz-based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1-13.7, p < 0.001, and AOR 5.6, 95% CI 2.1-15.2, p = 0.001, respectively).ConclusionsIn this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI-based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.

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Introduction: Multimonth dispensing (MMD) of antiretroviral treatment (ART) aims to reduce patient-related barriers to access long-term treatment and improve health system efficiency. However, randomized evidence of its clinical effectiveness is lacking. We compared MMD within community ART refill groups (CARGs) vs. standard-of-care facility-based ART delivery in Zimbabwe. Methods: A three-arm, cluster-randomized, pragmatic noninferiority trial was performed. Thirty health care facilities and associated CARGs were allocated to either ART collected three-monthly at facility (3MF, control); ART delivered three-monthly in CARGs (3MC); or ART delivered six-monthly in CARGs (6MC). Stable adults receiving ART $six months with baseline viral load (VL) ,1000 copies/ml were eligible. Retention in ART care (primary outcome) and viral suppression (VS) 12 months after enrollment were compared, using regression models specified for clustering (ClinicalTrials.gov: NCT03238846). Results: 4800 participants were recruited, 1919, 1335, and 1546 in arms 3MF, 3MC, and 6MC, respectively. For retention, the prespecified noninferiority limit (-3.25%, risk difference [RD]) was met for comparisons between all arms, 3MC (94.8%) vs. 3MF (93.0%), adjusted RD = 1.1% (95% CI:-0.5% to 2.8%); 6MC (95.5%) vs. 3MF: aRD = 1.2% (95% CI:-1.0% to 3.6%); and 6MC vs. 3MC: aRD = 0.1% (95% CI:-2.4% to 2.6%). VL completion at 12 months was 49%, 45%, and 8% in 3MF, 3MC, and 6MC, respectively. VS in 3MC (99.7%) was high and not different to 3MF (99.1%), relative risk = 1.0 (95% CI: 1.0-1.0). VS was marginally reduced in 6MC (92.9%) vs. 3MF, relative risk = 0.9 (95% CI: 0.9-1.0). Conclusion: Retention in CARGs receiving three-and six-monthly MMD was noninferior versus standard-of-care facility-based ART delivery. VS in 3MC was high. VS in six-monthly CARGs requires further evaluation.

Improved health outcomes have resulted in people with HIV facing decisions about childbearing. We sought to understand factors associated with desire for a child among men and women in Malawi. HIV-infected men and women ages 18-40 were invited to participate in a brief interview about fertility desires. Single variable logistic regression was used to evaluate factors associated with the outcome of fertility desire. Additionally, multiple logistic regression was used to assess the relationship of all the factors together on the outcome of fertility desire. In-depth interviews with women were performed to understand experiences with reproductive healthcare. A total of 202 brief interviews were completed with 75 men (37.1%) and 127 women (62.9%), with 103 (51.0%) of respondents desiring a child. Being in a relationship (OR 3.48, 95% CI: 1.58 to 7.65, p = 0.002) and duration of HIV more than two years (OR 2.00, 95% CI: 1.08 to 3.67, p=0.03) were associated with increased odds of desire for a child. Age 36-40 years (OR 0.64, 95% CI: 0.46 to 0.90, p = 0.009) and having a living child (OR 0.24, 95% CI: 0.07 to 0.84, p=0.03) were associated with decreased odds of desire for a child. Seventy percent of women (n=19 of 27 respondents) completing semi-structured interviews who responded to the question about decision-making reported that their male partners made decisions about children, while the remainder reported the decision was collaborative (n=8, 30%). Eighty-six percent of women (n=36 of 42 respondents) reported no discussion or a discouraging discussion with a provider about having children. HIV-infected women and men in Malawi maintain a desire to have children. Interventions are needed to integrate safer conception into HIV care, to improve male participation in safer conception counseling, and to empower providers to help patients make decisions about reproduction free of discrimination and coercion.