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.

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.

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.

"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.

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.

Provider experiences with three- and six-month antiretroviral therapy dispensing for stable clients in Zambia.

Multi-month dispensing of antiretroviral therapy (ART) has been taken to scale in many settings in sub-Saharan Africa with the benefits of improved client satisfaction and decreased client costs. Six-month ART dispensing may further increase these benefits; however, data are lacking. Within a cluster-randomized trial of three- versus six-month dispensing in Malawi and Zambia, we performed a sub-study to explore Zambian provider experiences with multi-month dispensing. We conducted 18 in-depth interviews with clinical officers and nurses dispensing ART as part of INTERVAL in Zambia. Interview questions focused on provider perceptions of client acceptability, views on client sharing and selling of ART, and perceptions on provider workload and clinic efficiency, with a focus on differences between three- and six-month dispensing. Interviews were analyzed using inductive thematic analysis to identify key themes and patterns within the data. Providers perceived significant benefits of multi-month dispensing, with advantages of six-month over three-month dispensing related to a reduced burden on clients, and for reductions in their own workload and clinic congestion. Among nearly all providers, the six-month dispensing strategy was perceived as ideal. Further research is needed to quantify clinical outcomes of six-month dispensing and feasibility of scaling-up this intervention in resource-limited settings.Clinical Trial Number: NCT03101592.

Barriers and facilitators to facility HIV self-testing in outpatient settings in Malawi: a qualitative study.

BACKGROUND: Facility HIV self-testing (HIVST) within outpatient departments can increase HIV testing coverage by facilitating HIVST use in outpatient waiting spaces while clients wait for routine care. Facility HIVST allows for the majority of outpatients to test with minimal health care worker time requirements. However, barriers and facilitators to outpatients' use of facility HIVST are still unknown. METHODS: As part of a cluster randomized trial on facility HIVST in Malawi, we conducted in-depth interviews with 57 adult outpatients (> 15 years) who were exposed to the HIVST intervention and collected observational journals that documented study staff observations from facility waiting spaces where HIVST was implemented. Translated and transcribed data were analyzed using constant comparison analysis in Atlas.ti. RESULTS: Facility HIVST was convenient, fast, and provided autonomy to outpatients. The strategy also had novel facilitators for testing, such as increased motivation to test due to seeing others test, immediate support for HIVST use, and easy access to additional HIV services in the health facility. Barriers to facility HIVST included fear of judgment from others and unwanted status disclosure due to lack of privacy. Desired changes to the intervention included private, separate spaces for kit use and interpretation and increased opportunity for disclosure and post-test counseling. CONCLUSIONS: Facility HIVST was largely acceptable to outpatients in Malawi with novel facilitators that are unique to facility HIVST in OPD waiting spaces. TRIAL REGISTRATION: The parent trial is registered with ClinicalTrials.gov , NCT03271307 , and Pan African Clinical Trials, PACTR201711002697316.

"A loving man has a very huge responsibility": A mixed methods study of Malawian men's knowledge and beliefs about cervical cancer.

BACKGROUND: In Malawi, numerous barriers may prevent women from accessing cervical cancer screening services - including social factors such as male partner involvement. We conducted surveys that included open- and closed-ended questions with married Malawian men to evaluate their knowledge and beliefs about cervical cancer. METHODS: HIV-positive adult (≥18 years) men (married or in a stable relationship) were recruited from an antiretroviral therapy clinic in Lilongwe, Malawi. Men were asked a series of survey questions to assess their knowledge about cervical cancer, experience with cervical cancer, their female partner's screening history, and their beliefs about gender norms and household decision-making. Following the survey, participants responded to a set of open-ended interview questions about cervical cancer screening, and men's role in prevention. RESULTS: One hundred-twenty men were enrolled with average age 44 years and 55% having completed secondary school or higher education. Despite only moderate knowledge about cervical cancer and screening (average assessment score of 62% correct), all men expressed support of cervical cancer screening, and most (86%) believed they should be involved in their female partner's decision to be screened. Over half (61%) of men said their female partner had previously been screened for cervical cancer, and this was positively correlated with the male respondent having more progressive gender norms around sexual practices. Some men expressed concerns about the screening process, namely the propriety of vaginal exams when performed by male clinicians, and whether the procedure was painful. CONCLUSIONS: Male partners in Malawi want to be involved in decisions about cervical cancer screening, but have limited knowledge about screening, and hold rigid beliefs about gender norms that may affect their support for screening. Messaging campaigns addressing men's concerns may be instrumental in improving women's adoption of cervical cancer screening services in Malawi and similar settings.

Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy.

Background: Adverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting. Methods: Human immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts ≥400 cells/µL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm. Results: Subsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/µL (IQR, 492-833 cells/µL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4]). Conclusions: Women randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens.

ART Adherence Among Malawian Youth Enrolled in Teen Clubs: A Retrospective Chart Review.

To improve outcomes among HIV-positive adolescents, the Malawi Ministry of Health is supporting scale-up of "Teen Clubs," a facility-based antiretroviral treatment (ART) delivery model. Teen Clubs are monthly ART clinics for adolescents (10-19 years old) that provide clinical services and peer psychosocial support. This paper assesses ART adherence among Teen Club attendees in Malawi. We performed a retrospective analysis of medical records and Teen Club attendance data on 589 HIV-positive adolescents at 16 Partners in Hope (PIH)-Extending Quality Improvement for HIV/AIDS in Malawi (EQUIP) supported facilities across Malawi, from January to June of 2017, who attended at least two Teen Club sessions. Multi-level logistic regression models were used to examine the role of gender and age on optimal ART adherence (≥ 95% based on pill count) among HIV-positive adolescents enrolled in Teen Clubs. The median age of adolescents in this sample was 14 years, and 47% were male. Older adolescent males (15-19 years) were 64% more likely to achieve ≥ 95% ART adherence (aOR 1.64, 95% CI 1.16-2.31, p < 0.01) compared to younger (10-14 years) males. The effect of age on adherence was smaller and not significant among females (aOR 1.36, 95% CI 0.96-1.94, p = 0.08). In the full model including males and females, older adolescence was associated with higher odds of optimal adherence (aOR 1.48, 95% CI 1.16-1.90, p < 0.01). These results reinforce the need for age-specialized programming for adolescents, and future research should evaluate this in achieving optimal ART adherence.

Benefits of PrEP as an Adjunctive Method of HIV Prevention During Attempted Conception Between HIV-uninfected Women and HIV-infected Male Partners.

BACKGROUND: Data on effectiveness of preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV)-uninfected women attempting conception with HIV-infected male partners are limited to observational studies. METHODS: To explore the benefits of PrEP for conception, we developed a model to estimate the average annual probability of a woman remaining HIV-uninfected and having a child ("successful" outcome) via condomless sex with an HIV-infected male. The outcome likelihood is dependent upon parameters defining HIV-1 infectivity. We simulated 2 scenarios: optimal (condomless sex acts limited to the ovulation window), and suboptimal (acts not limited to ovulation). RESULTS: In the optimal scenario when the male is on antiretroviral therapy (ART), the average annual probability of the successful outcome is 29.1%, increasing to 29.2% with the addition of PrEP (P = .45). In the suboptimal scenario, the probability is 26.8% with ART alone versus 27.3% with ART/PrEP (P < .0001). Older maternal age reduces the probability of success in both scenarios, particularly after age 30. CONCLUSIONS: In our model, PrEP provides little added benefit when the HIV-infected male partner is on ART, condomless sex is limited to the ovulation window, and other modifiable transmission risks are optimized. Older female age decreases the probability of success by increasing the number of condomless sex acts required for conception.

Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy.

BACKGROUND: HIV infection and antiretroviral therapy (ART) may create unique risk factors for vitamin D insufficiency, including alterations of vitamin D metabolism by ART. We prospectively compared demographic and clinical parameters between vitamin D sufficient and insufficient HIV-infected (HIV+) adults, and assessed changes in these parameters among insufficient participants following standardized vitamin D supplementation. METHODS: HIV+ adults (≥ 18 years old) with HIV-1 RNA <50 copies/mL on ART were enrolled. Vitamin D sufficiency and insufficiency were defined as 25-hydroxyvitamin D (25(OH)D) ≥ 30 or <30 ng/mL, respectively. Insufficient participants received open-label vitamin D3 50,000 IU twice weekly for 5 weeks, then 8000 IU twice weekly to complete 24 weeks. The primary endpoint was success or failure to achieve 25(OH)D ≥ 30 ng/mL at week 24. RESULTS: Ninety-seven participants enrolled (34 vitamin D sufficient, 63 insufficient); 32% female, 47% non-White, median age 46 years, ART duration 5 years, CD4+ T lymphocyte count (CD4) 673 cells/mm(3). 25(OH)D repletion was 83% (95% CI 71%-90%) successful. 25(OH)D levels correlated with both CD4 (r = 0.44, p = 0.01) and time on protease inhibitor (r = -0.35, p = 0.01). After adjusting for age, sex, race, nadir CD4 and baseline 25(OH)D: 1) current use of efavirenz exposure was associated with a 21.1 ng/mL higher week 24 25(OH)D level (p = 0.007), 2) per year use of zidovudine was associated with 7.1 ng/mL reduction in week 24 serum 25(OH)D (p = 0.05) and 3) every 1 ng/mL 25(OH)D increase was associated with a 3.3 cell/mm(3) CD4 increase (p = 0.06). CONCLUSION: Vitamin D3 supplementation was effective in repleting 25(OH)D levels after 24 weeks. Current efavirenz use was positively associated with post-repletion 25(OH)D levels, while greater time on zidovudine was associated with lower post-repletion 25(OH)D levels. The association between improved CD4 recovery and vitamin D repletion suggests a potential benefit of vitamin D supplementation on immunologic recovery during HIV treatment. TRIAL REGISTRATION: This trial is registered at The Brazilian Clinical Trials Registry (U1111-1165-2537).