Weight Changes and Adverse Pregnancy Outcomes With Dolutegravir- and Tenofovir Alafenamide Fumarate-Containing Antiretroviral Treatment Regimens During Pregnancy and Postpartum.

BACKGROUND: We evaluated associations between antepartum weight change and adverse pregnancy outcomes and between antiretroviral therapy (ART) regimens and week 50 postpartum body mass index in IMPAACT 2010. METHODS: Women with human immunodeficiency virus (HIV)-1 in 9 countries were randomized 1:1:1 at 14-28 weeks' gestational age (GA) to start dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) versus DTG + FTC/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF. Insufficient antepartum weight gain was defined using Institute of Medicine guidelines. Cox-proportional hazards regression models were used to evaluate the association between antepartum weight change and adverse pregnancy outcomes: stillbirth (≥20 weeks' GA), preterm delivery (<37 weeks' GA), small size for GA (<10th percentile), and a composite of these endpoints. RESULTS: A total of 643 participants were randomized: 217 to the DTG + FTC/TAF, 215 to the DTG + FTC/TDF, and 211 to the EFV/FTC/TDF arm. Baseline medians were as follows: GA, 21.9 weeks; HIV RNA, 903 copies/mL; and CD4 cell count, 466/µL. Insufficient weight gain was least frequent with DTG + FTC/TAF (15.0%) versus DTG + FTC/TDF (23.6%) and EFV/FTC/TDF (30.4%). Women in the DTG + FTC/TAF arm had the lowest rate of composite adverse pregnancy outcome. Low antepartum weight gain was associated with higher hazard of composite adverse pregnancy outcome (hazard ratio, 1.44 [95% confidence interval, 1.04-2.00]) and small size for GA (1.48 [.99-2.22]). More women in the DTG + FTC/TAF arm had a body mass index ≥25 (calculated as weight in kilograms divided by height in meters squared) at 50 weeks postpartum (54.7%) versus the DTG + FTC/TDF (45.2%) and EFV/FTC/TDF (34.2%) arms. CONCLUSIONS: Antepartum weight gain on DTG regimens was protective against adverse pregnancy outcomes typically associated with insufficient weight gain, supportive of guidelines recommending DTG-based ART for women starting ART during pregnancy. Interventions to mitigate postpartum weight gain are needed.

Cost-effectiveness of approaches to cervical cancer screening in Malawi: comparison of frequencies, lesion treatment techniques, and risk-stratified approaches.

BACKGROUND: Recently-updated global guidelines for cervical cancer screening incorporated new technologies-most significantly, the inclusion of HPV DNA detection as a primary screening test-but leave many implementation decisions at countries' discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening. METHODS: Using a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing "triage" approaches-i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software. RESULTS: Thermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach. CONCLUSIONS: These results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.

Effect of index HIV self-testing for sexual partners of clients enrolled in antiretroviral therapy (ART) programs in Malawi: A randomized controlled trial.

BACKGROUND: HIV testing among the sexual partners of HIV-positive clients is critical for case identification and reduced transmission in southern and eastern Africa. HIV self-testing (HIVST) may improve uptake of HIV services among sexual partners of antiretroviral therapy (ART) clients, but the impact of HIVST on partner testing and subsequent ART initiation remains unclear. METHODS AND FINDINGS: We conducted an individually randomized, unblinded trial to assess if an index HIVST intervention targeting the partners of ART clients improves uptake of testing and treatment services in Malawi. The trial was conducted at 3 high-burden facilities in central and southern Malawi. ART clients attending HIV treatment clinics were randomized using simple randomization 1:2·5 to: (1) standard partner referral slip (PRS) whereby ART clients were given facility referral slips to distribute to their primary sexual partners; or (2) index HIVST whereby ART clients were given HIVST kits + HIVST instructions and facility referral slips to distribute to their primary sexual partners. Inclusion criteria for ART clients were: ≥15 years of age, primary partner with unknown HIV status, no history of interpersonal violence (IPV) with partner, and partner lives in facility catchment area. The primary outcome was partner testing 4-weeks after enrollment, reported by ART clients using endline surveys. Medical chart reviews and tracing activities with partners with a reactive HIV test measured ART initiation at 12 months. Analyses were conducted based on modified intention-to-treat principles, whereby we excluded individuals who did not have complete endline data (i.e., were loss to follow up from the study). Adjusted models controlled for the effects of age and marital status. A total of 4,237 ART clients were screened and 484 were eligible and enrolled (77% female) between March 28, 2018 and January 5, 2020. A total of 365 participants completed an endline survey (257/34 index HIVST arm; 107/13 PRS arm) and were included in the final analysis (78% female). Testing coverage among sexual partners was 71% (183/257) in the index HIVST arm and 25% (27/107) in the PRS arm (aRR: 2·77, 95% CI [2·56 to 3·00], p ≤ 0.001). Reported HIV positivity rates did not significantly differ by arm (16% (30/183) in HIVST versus 15% (4/27) in PRS; p = 0.99). ART initiation at 12 months was 47% (14/30) in HIVST versus 75% (3/4) in PRS arms; however, index HIVST still resulted in a 94% increase in the proportion of all partners initiating ART due to higher HIV testing rates in the HIVST arm (5% partners initiated ART in HVIST versus 3% in PRS). Adverse events including IPV and termination of the relationship did not vary by arm (IPV: 3/257 index HIVST versus 4/10 PRS; p = 0.57). Limitations include reliance on secondary report by ART clients, potential social desirability bias, and not powered for sex disaggregated analyses. CONCLUSIONS: Index HIVST significantly increased HIV testing and the absolute number of partners initiating ART in Malawi, without increased risk of adverse events. Additional research is needed to improve linkage to HIV treatment services after HIVST use. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03271307, and Pan African Clinical Trials, PACTR201711002697316.

Strategies to improve antiretroviral therapy (ART) initiation and early engagement among men in sub-Saharan Africa: A scoping review of interventions in the era of universal treatment.

OBJECTIVES: Men in sub-Saharan Africa (SSA) have lower rates of antiretroviral therapy (ART) initiation and higher rates of early default than women. Little is known about effective interventions to improve men's outcomes. We conducted a scoping review of interventions aimed to increase ART initiation and/or early retention among men in SSA since universal treatment policies were implemented. METHODS: Three databases, HIV conference databases and grey literature were searched for studies published between January 2016 to May 2021 that reported on initiation and/or early retention among men. Eligibility criteria included: participants in SSA, data collected after universal treatment policies were implemented (2016-2021), quantitative data on ART initiation and/or early retention for males, general male population (not exclusively focused on key populations), intervention study (report outcomes for at least one non-standard service delivery strategy), and written in English. RESULTS: Of the 4351 sources retrieved, 15 (reporting on 16 interventions) met inclusion criteria. Of the 16 interventions, only two (2/16, 13%) exclusively focused on men. Five (5/16, 31%) were randomised control trials (RCT), one (1/16, 6%) was a retrospective cohort study, and 10 (10/16, 63%) did not have comparison groups. Thirteen (13/16, 81%) interventions measured ART initiation and six (6/16, 37%) measured early retention. Outcome definitions and time frames varied greatly, with seven (7/16, 44%) not specifying time frames at all. Five types of interventions were represented: optimising ART services at health facilities, community-based ART services, outreach support (such as reminders and facility escort), counselling and/or peer support, and conditional incentives. Across all intervention types, ART initiation rates ranged from 27% to 97% and early retention from 47% to 95%. CONCLUSIONS: Despite years of data of men's suboptimal ART outcomes, there is little high-quality evidence on interventions to increase men's ART initiation or early retention in SSA. Additional randomised or quasi-experimental studies are urgently needed.

Understanding the Unique Barriers and Facilitators that Affect Men's Initiation and Retention in HIV Care: A Qualitative Study to Inform Interventions for Men Across the Treatment Cascade in Malawi.

Men in sub-Saharan Africa are underrepresented in antiretroviral therapy (ART) programs. Our secondary analysis of 40 in-depth interviews with Malawian men living with HIV examined barriers and facilitators for ART initiation versus retention. Interviewees included men who never initiated or initiated ART late (initiation respondents, n = 19); and men who initiated ART but were late for an appointment (retention respondents, n = 21). Transcribed interviews were coded using deductive and inductive coding techniques and analyzed using constant comparison methods. Long wait times, frequent facility visits, and insufficient in-clinic privacy were barriers for initiation and retention. Poor knowledge of ART was primarily a barrier for initiation; unexpected travel was a barrier for retention. Key facilitators for initiation and retention included previous positive experiences with health facilities. Having examples of successful men using ART primarily facilitated initiation; support from spouses and male peers facilitated retention. Results may inform interventions to increase men's engagement in ART services.

Experiences with telemedicine for HIV care in two federally qualified health centers in Los Angeles: a qualitative study.

BACKGROUND: The SARS-CoV-2 pandemic has resulted in an increase in telemedicine utilization for routine HIV care. However, there is limited information on perceptions of and experiences with telemedicine from United States (U.S.) federally qualified health centers (FQHCs) offering HIV care. We sought to understand telemedicine experiences of stakeholders with various roles: people living with HIV (PLHIV), clinical (clinicians and case managers), programmatic (clinic administrators), and policy (policymakers). METHODS: Qualitative interviews about benefits and challenges of telemedicine (telephone and video) for HIV care were conducted with 31 PLHIV and 23 other stakeholders (clinicians, case managers, clinic administrators, and policymakers). Interviews were transcribed, translated to English if conducted in Spanish, coded, and analyzed for major themes. RESULTS: Almost all PLHIV felt capable of engaging in telephone visits, with some expressing interest in learning how to use video visits as well. Nearly all PLHIV wanted to continue telemedicine as part of their routine HIV care, and this was also endorsed by clinical, programmatic and policy stakeholders. Interviewees agreed that telemedicine for HIV care has benefits for PLHIV, especially savings of time and transportation costs, which also reduced stress. Clinical, programmatic, and policy stakeholders expressed concerns around patients' technological literacy and resources, as well as their access to privacy, and some felt that PLHIV strongly preferred in-person visits. These stakeholders also commonly reported clinic-level implementation challenges, including integrating telephone and video telemedicine into workflows and difficulty with video visit platforms. CONCLUSIONS: Telemedicine for HIV care, largely delivered via telephone (audio-only), was highly acceptable and feasible for both PLHIV, clinicians, and other stakeholders. Addressing barriers for stakeholders in incorporating video visits will be important for the successful implementation of telemedicine with video as part of routine HIV care at FQHCs.

Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA-Positive Samples.

While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.

Self-Assessed Severity as a Determinant of Coronavirus Disease 2019 Symptom Specificity: A Longitudinal Cohort Study.

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%- 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%).

Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Antiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate. METHODS: This multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422. FINDINGS: Between Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of <200 copies per mL), and the median CD4 count was 466 cells per µL (308-624). HIV-1 RNA concentrations at delivery were available for 605 (94%) participants. Of these, 395 (98%) of 405 participants in the combined dolutegravir-containing groups had viral suppression at delivery compared with 182 (91%) of 200 participants in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (estimated difference 6·5% [95% CI 2·0 to 10·7], p=0·0052; excluding the non-inferiority margin of -10%). Significantly fewer participants in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (52 [24%] of 216) had a composite adverse pregnancy outcome than those in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (70 [33%] of 213; estimated difference -8·8% [95% CI -17·3 to -0·3], p=0·043) or the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (69 [33%] of 211; -8·6% [-17·1 to -0·1], p=0·047). The proportion of participants or infants with grade 3 or higher adverse events did not differ among the three groups. The proportion of participants who had a preterm delivery was significantly lower in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (12 [6%] of 208) than in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (25 [12%] of 207; -6·3% [-11·8 to -0·9], p=0·023). Neonatal mortality was significantly higher in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (ten [5%] of 207 infants) than in the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group (two [1%] of 208; p=0·019) or the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (three [2%] of 202; p=0·050). INTERPRETATION: When started in pregnancy, dolutegravir-containing regimens had superior virological efficacy at delivery compared with the efavirenz, emtricitabine, and tenofovir disoproxil fumarate regimen. The dolutegravir, emtricitabine, and tenofovir alafenamide fumarate regimen had the lowest frequency of composite adverse pregnancy outcomes and of neonatal deaths. FUNDING: National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Screening Adults for HIV Testing in the Outpatient Department: An Assessment of Tool Performance in Malawi.

Little is known about screening tools for adults in high HIV burden contexts. We use exit survey data collected at outpatient departments in Malawi (n = 1038) to estimate the sensitivity, specificity, negative and positive predictive values of screening tools that include questions about sexual behavior and use of health services. We compare a full tool (seven relevant questions) to a reduced tool (five questions, excluding sexual behavior measures) and to standard of care (two questions, never tested for HIV or tested > 12 months ago, or seeking care for suspected STI). Suspect STI and ≥ 3 sexual partners were associated with HIV positivity, but had weak sensitivity and specificity. The full tool (using the optimal cutoff score of ≥ 3) would achieve 55.6% sensitivity and 84.9% specificity for HIV positivity; the reduced tool (optimal cutoff score ≥ 2) would achieve 59.3% sensitivity and 68.5% specificity; and standard of care 77.8% sensitivity and 47.8% specificity. Screening tools for HIV testing in outpatient departments do not offer clear advantages over standard of care.

Mediators and moderators of ART adherence effects of supporting treatment adherence readiness through training (START): evidence that START helps vulnerable clients achieve better adherence.

Supporting Treatment Adherence Readiness through Training (START) is an HIV antiretroviral adherence intervention, based on the Information Motivation and Behavioral skills (IMB) model, that significantly improved adherence in our randomized controlled trial. To understand how and for whom START had its effects on adherence, we examined mediators and moderators. Ninety-nine HIV-patients (53 control, 46 intervention) who enrolled in the trial and provided month 6 electronic monitored adherence data. The intervention was associated with increased adherence-related knowledge and lower impulsive/careless problem solving, but had no effects on other IMB-related constructs. Neither of these variables mediated the adherence effects of the intervention (based on linear regression models with bootstraping for unbiased standard errors). Four variables interacted with the intervention to moderate its effects: the intervention group had consistent high adherence across the range of depression and time since HIV diagnosis, compared to lower adherence with higher values in the usual care control; those with unstable housing or frequent drug use had higher adherence if in the intervention group compared to the control group. These findings suggest that START provides support that enables its recipients to cope with and overcome challenges (e.g., depression, unstable housing, drug use) that would typically impede adherence.Trial registration: ClinicalTrials.gov identifier: NCT02329782.

Gendered differences in perceptions and reports of wellbeing: A cross-sectional survey of adults on ART in Malawi.

Few studies have examined gender differences in reported quality of life among persons living with HIV (PLWH) in low-income countries. We conducted a cross-sectional survey of adults on antiretroviral therapy in Malawi, including questions focused on wellbeing, and collected clinical data on these respondents. We compared men's and women's self-reported health and wellbeing using Poisson models that included socio-demographic covariates. Approximately 20% of respondents reported at least one physical functioning problem. In multiple variable models, men were significantly more likely to have a high viral load (≥200 copies/mL; aIRR 2.57), consume alcohol (aIRR 12.58), receive no help from family or friends (aIRR 2.18), and to feel worthless due to their HIV status (aIRR 2.40). Men were significantly less likely to be overweight or obese (aIRR 0.31), or report poor health (health today is not "very good;" aIRR 0.41). Taken together, despite higher prevalence of poor self-rated health, women were healthier across a range of objective dimensions, with better viral suppression, less alcohol use, and less social isolation (although they were more likely to have an unhealthy BMI). Research that includes multi-dimensional and gender-specific measurement of physical, mental and social health is important for improving our understanding of well-being of PLWH.

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.

BACKGROUND: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING: National U.S. multicenter study. PARTICIPANTS: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026). LIMITATION: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.

"When You Have Gotten Help, That Means You Were Strong": A Qualitative Study of Experiences in a "Screen and Treat" Program for Cervical Cancer Prevention in Malawi.

Disproportionate cervical cancer burden falls on women in low-income countries, and there are new efforts to scale up prevention worldwide, including via "screen and treat" for detection and removal of abnormal cervical lesions. This study examines Malawian women's experiences with "screen and treat"; this is an under-explored topic in the literature, which has focused largely on knowledge about and attitudes toward screening, but not on experiences with screening. We interviewed 47 women who have been screened at least once for cervical cancer. The interview guide and analysis approach were informed by the Multi-Level Health Outcomes Framework. Women were recruited at facilities that offer "screen and treat" and asked about their experiences with screening. The average age of respondents was 40 years, and approximately half were HIV-negative. Although women were knowledgeable about the benefits of screening, they articulated many barriers including being turned away because of stock-outs of equipment, far distances to services, discomfort with male providers, and poor communication with providers. Alongside the many health education campaigns to increase awareness and demand for "screen and treat" services, the global public health community must also address implementation barriers in the resource-constrained health systems where burden is greatest. Particular attention should be paid to quality and person-centeredness of "screen and treat" services to optimize uptake and engagement in care.

Pregnancy Outcomes of Women Conceiving on Antiretroviral Therapy (ART) Compared to Those Commenced on ART During Pregnancy.

BACKGROUND: Globally, the number of infected women of childbearing age living with human immunodeficiency virus (HIV) and conceiving on antiretroviral therapy (ART) is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The Promoting Maternal and Infant Survival Everywhere (PROMISE) 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. METHODS: The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of nonbreastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who restarted ART after pregnancy was diagnosed. RESULTS: Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (<2500 g) for women who conceived while on ART (relative risk, 2.65 [95% confidence interval {CI}, 1.20-5.81]), and also a higher risk of spontaneous abortion, stillbirth, or neonatal death (hazard ratio, 1.40 [95% CI, .99-1.98]) compared to women who restarted ART after they were found to be pregnant during trial follow-up. CONCLUSIONS: We found an increased risk for adverse pregnancy outcomes in women conceiving on ART, emphasizing the need for improved obstetric and neonatal care for this group. CLINICAL TRIALS REGISTRATION: NCT01061151.

Birth Outcomes for Pregnant Women with HIV Using Tenofovir-Emtricitabine.

BACKGROUND: In a previous trial of antiretroviral therapy (ART) involving pregnant women with human immunodeficiency virus (HIV) infection, those randomly assigned to receive tenofovir, emtricitabine, and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) had infants at greater risk for very premature birth and death within 14 days after delivery than those assigned to receive zidovudine, lamivudine, and ritonavir-boosted lopinavir (ZDV-3TC-LPV/r). METHODS: Using data from two U.S.-based cohort studies, we compared the risk of adverse birth outcomes among infants with in utero exposure to ZDV-3TC-LPV/r, TDF-FTC-LPV/r, or TDF-FTC with ritonavir-boosted atazanavir (ATV/r). We evaluated the risk of preterm birth (<37 completed weeks of gestation), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and very low birth weight (<1500 g). Risk ratios with 95% confidence intervals were estimated with the use of modified Poisson models to adjust for confounding. RESULTS: There were 4646 birth outcomes. Few infants or fetuses were exposed to TDF-FTC-LPV/r (128 [2.8%]) as the initial ART regimen during gestation, in contrast with TDF-FTC-ATV/r (539 [11.6%]) and ZDV-3TC-LPV/r (954 [20.5%]). As compared with women receiving ZDV-3TC-LPV/r, women receiving TDF-FTC-LPV/r had a similar risk of preterm birth (risk ratio, 0.90; 95% confidence interval [CI], 0.60 to 1.33) and low birth weight (risk ratio, 1.13; 95% CI, 0.78 to 1.64). As compared to women receiving TDF-FTC-ATV/r, women receiving TDF-FTC-LPV/r had a similar or slightly higher risk of preterm birth (risk ratio, 1.14; 95% CI, 0.75 to 1.72) and low birth weight (risk ratio, 1.45; 95% CI, 0.96 to 2.17). There were no significant differences between regimens in the risk of very preterm birth or very low birth weight. CONCLUSIONS: The risk of adverse birth outcomes was not higher with TDF-FTC-LPV/r than with ZDV-3TC-LPV/r or TDF-FTC-ATV/r among HIV-infected women and their infants in the United States, although power was limited for some comparisons. (Funded by the National Institutes of Health and others.).

Non-communicable Diseases in Pregnant and Postpartum Women Living with HIV: Implications for Health Throughout the Life Course.

PURPOSE OF REVIEW: The development of non-communicable diseases (NCDs) in pregnant women living with HIV can be a harbinger of future NCD-related morbidity and mortality. This review focuses on the NCDs that complicate pregnancy and the postpartum period, including hypertensive complications, hyperglycemic disorders, excessive gestational weight gain, and bone mineral density losses. For each disease process, we explore the role of HIV as a possible driver of excess risk, the immediate consequences of these complications on pregnancy outcomes and maternal and infant health, and possible implications for long-term women's health. RECENT FINDINGS: Countries with the highest burden of HIV also shoulder a high burden of NCDs that complicate pregnancy, including hypertensive disorders, hyperglycemic disorders, weight gain, and osteopenia. This double burden of disease is a significant public health threat for reproductive-age women, with the potential for serious short- and long-term consequences for both women and their infants. Additionally, as the global first-line antiretroviral therapy regimens increasingly include integrase inhibitors, unhealthy weight gain associated with this drug class poses additional risk for NCD-related pregnancy complications and their persistence postpartum. Further research is needed to better define prevalence of NCD complications in pregnancy, elucidate HIV-specific and traditional factors associated with poor outcomes, and to develop interventions to reduce risk and avoid downstream complications in those at highest risk.

Examining Correlates of Pre-ART and Early ART Adherence to Identify Key Factors Influencing Adherence Readiness.

Although current standard of care for HIV typically involves immediate initiation of antiretroviral therapy (ART), most patients can benefit from first assessing adherence readiness and addressing any barriers to optimal adherence. A sample of 176 HIV patients planning to start ART enrolled in a controlled trial of an adherence intervention that was based on the Information Motivation and Behavioral skills (IMB) model of health behavior. We examined correlates of multiple adherence readiness measures, as well as electronically measured early ART adherence, to identify variables most important for readiness to adhere well at the start of treatment. Education level, recency of HIV diagnosis and knowledge and commitment to adherence were found to be associated with both ART readiness and early ART adherence. These findings suggest that resources to support adherence readiness should target more experienced HIV patients, and strive to bolster knowledge and attitudes that reinforce commitment to adherence.

A Multi-Dimensional Characterization of Aging and Wellbeing Among HIV-Positive Adults in Malawi.

There is relatively little research on aging with HIV and wellbeing in sub-Saharan Africa. A cross-sectional survey was implemented in Malawi; eligible respondents were ≥ 30 years old and on ART for ≥ 2 years. Univariate and multiple regression analyses were stratified by age (younger adults: aged 30-49; older adults: aged ≥ 50) and gender. The median age was 51 years (total sample n = 134). Viral suppression was less common among older respondents (83.7% versus 93.0% among younger respondents) although not significant in adjusted models. Despite exhibiting worse physical and cognitive functioning (any physical functioning challenge: aOR 5.35, p = 0.02; cognitive functioning score difference: - 0.89 points, p = 0.04), older adults reported less interpersonal violence and fewer depressive symptoms (mild depression: aOR 0.23 p = 0.002; major depression: aOR 0.16, p = 0.004); in gender-stratified models, these relationships were significant only for females. More research is needed to disentangle the interplay between aging, gender and HIV in high-burden contexts and develop interventions to support comprehensive wellbeing in this population.

START (Supporting Treatment Adherence Readiness through Training) Improves Both HIV Antiretroviral Adherence and Viral Reduction, and is Cost Effective: Results of a Multi-site Randomized Controlled Trial.

The START (Supporting Treatment Adherence Readiness through Training) intervention was examined for its effects on ART adherence and virologic suppression relative to usual care. A sample of 176 clients about to start or restart ART were randomized (83 to START, 93 to usual care) at HIV clinics in the Los Angeles area. Primary outcomes included electronically monitored dose-taking adherence and HIV viral load; primary end points were months 6 and 24, with group differences examined using nonresponse-weighted means or proportions, effect sizes, and significance testing. Item nonresponse was addressed using multiple imputation. 166 (94.3%) participants started ART, of whom 124 (74.7%) were still in care at month 6, and 90 (54.2%) at month 24. In comparison to the usual care control group, the START group had higher dose-taking adherence at month 6 (86.2% vs. 71.6%, d = 0.56, p = 0.01), which was sustained through month 24 (86.0% vs. 61.1%, d =1.01, p < 0.0001). While rates of undetectable viral load did not differ between groups at month 6 or 24, the mean reduction in viral load (log10 copies/mm3) at month 24 was significantly greater in the intervention arm (3.0 vs. 2.7; d = 0.40, p = 0.047). An estimated cost of $132 per person was needed to obtain a 10% increase in dose-taking adherence over 24 months from the intervention. These findings suggest that START is cost effective in producing a medium to large effect on dose-taking adherence that is durable over 24 months, and a modest long-term effect on viral reduction.Trial registration Clinicaltrials.gov NCT02329782 (registered December 22, 2014).