Assessing Per-Sex-Act HIV-1 Risk Reduction Among Women Using the Dapivirine Vaginal Ring.

BACKGROUND: Confounding introduced by individuals' sexual risk behavior is potentially a significant source of bias in HIV-1 prevention intervention studies. To more completely account for sexual behaviors when assessing the efficacy of the monthly dapivirine ring, a new longer-acting HIV-1 prevention option for women, we estimated per-sex-act risk reduction associated with product use. METHODS: We conducted a secondary analysis of data from MTN-020/ASPIRE, a phase 3, randomized, placebo-controlled efficacy trial of the dapivirine ring that recruited HIV-uninfected, African women aged 18-45 years. With cumulative sex acts as the time scale, we used multivariable Cox regression with inverse probability of censoring weights to estimate HIV-1 risk reduction associated with a rate of dapivirine release indicative of consistent product use. RESULTS: Women in the dapivirine ring group (n = 1187) had an estimated incidence rate of 2.3 (95% confidence interval [CI], 1.8-3.1) HIV-1 acquisition events per 10 000 sex acts versus 3.6 (95% CI, 2.9-4.4) per 10 000 acts in the placebo group (n = 1187). Dapivirine release indicative of consistent ring use was associated with a 63% (95% CI, 33%-80%) per-sex-act HIV-1 risk reduction. CONCLUSIONS: These results support the efficacy of the dapivirine vaginal ring for HIV-1 prevention and help to inform decision-making for women, providers, and policymakers regarding product use. CLINICAL TRIALS REGISTRATION: NCT01617096.

Lessons Learned from Public Health and State Prison Collaborations during COVID-19 Pandemic and Multifacility Tuberculosis Outbreak, Washington, USA.

The large COVID-19 outbreaks in prisons in the Washington (USA) State Department of Corrections (WADOC) system during 2020 highlighted the need for a new public health approach to prevent and control COVID-19 transmission in the system's 12 facilities. WADOC and the Washington State Department of Health (WADOH) responded by strengthening partnerships through dedicated corrections-focused public health staff, improving cross-agency outbreak response coordination, implementing and developing corrections-specific public health guidance, and establishing collaborative data systems. The preexisting partnerships and trust between WADOC and WADOH, strengthened during the COVID-19 response, laid the foundation for a collaborative response during late 2021 to the largest tuberculosis outbreak in Washington State in the past 20 years. We describe challenges of a multiagency collaboration during 2 outbreak responses, as well as approaches to address those challenges, and share lessons learned for future communicable disease outbreak responses in correctional settings.

Tuberculosis Outbreak in a State Prison System - Washington, 2021-2022.

During 2014-2020, no tuberculosis (TB) cases were reported within the Washington state prison system. However, during July 2021-June 2022, 25 TB cases were reported among persons incarcerated or formerly incarcerated in two Washington state prisons. Phylogenetic analyses of whole genome sequencing data indicated that Mycobacterium tuberculosis isolates from all 11 patients with culture-confirmed TB were closely related, suggesting that these cases represented a single outbreak. The median infectious period for 12 patients who were considered likely contagious was 170 days. As of November 15, 2022, the Washington State Department of Corrections (WADOC) and Washington State Department of Health (WADOH), with technical assistance from CDC, had identified 3,075 contacts among incarcerated residents and staff members at five state prisons, and 244 contacts without a known TB history received a diagnosis of latent TB infection (LTBI). Persons who were evaluated for TB disease were isolated; those receiving a diagnosis of TB then initiated antituberculosis therapy. Persons with LTBI were offered treatment to prevent progression to TB disease. This ongoing TB outbreak is the largest in Washington in 20 years. Suspension of annual TB screening while limited resources were redirected toward the COVID-19 response resulted in delayed case detection that facilitated TB transmission. In addition, fear of isolation might discourage residents and staff members from reporting symptoms, which likely also leads to delayed TB diagnoses. Continued close collaboration between WADOC and WADOH is needed to end this outbreak and prevent future outbreaks.

A novel "HIV salience and Perception" scale is associated with PrEP dispensing and adherence among adolescent girls and young women in Kampala, Uganda.

Low perceived HIV risk is a barrier to effective pre-exposure prophylaxis (PrEP) use among African adolescent girls and young women (AGYW). Single-item risk perception measures are stigmatizing and alienating to AGYW and may not predict PrEP use. There is a need for a tool capturing domains of perceived HIV risk and salience that align with PrEP use among AGYW. This HIV PrEP study was conducted in Kampala, Uganda. We developed and piloted the 9-item "HIV Salience and Perception" (HPS) scale (range: 9-36); higher scores indicate beliefs of higher vulnerability to HIV. We administered the scale to Ugandan AGYW participating in an ongoing cohort study at enrollment, one, three and six months. PrEP dispensing was measured quarterly and adherence was measured daily via Wisepill (high adherence: ≥80% of expected pill bottle openings). We assessed scale performance and used generalized estimating equations to determine associations between scale score and PrEP use. Among 499 AGYW, 54.1% of our sample was ≥ 20 years (range:16-25). The median HPS score was 18 (range:8-33; α = 0.77). Higher score was associated with PrEP dispensing (aRR = 1.07 per point increase; 95% CI = 1.01-1.13; p-value = 0.02) in the overall cohort and among only those ≥ 20 years (aRR = 1.10; 95% CI = 1.03-1.19; p-value = 0.01). We did not observe an association between scale score and PrEP adherence. AGYW scoring higher on a novel HPS scale were more likely to initiate and obtain PrEP refills through 6 months. This scale may capture drivers of PrEP dispensing and could inform PrEP delivery and counseling for AGYW.

Depression and PrEP uptake, interruption, and adherence among young women in Uganda.

Depression is a common cause of morbidity globally and can impact adherence to medications, posing challenges to medication-based HIV prevention. The objectives of this work are to describe the frequency of depression symptoms in a cohort of 499 young women in Kampala, Uganda and to determine the association of depression symptoms with use of HIV pre-exposure prophylaxis (PrEP). Mild or greater depression, assessed by the patient health questionnaire (PHQ-9), was experienced by 34% of participants at enrollment. Participants with mild depression symptoms tended to uptake PrEP, request PrEP refills, and adhere to PrEP with similar frequency to women with no/minimal signs of depression. These findings highlight opportunities to leverage existing HIV prevention programs to identify women who may benefit from mental health services and may not otherwise be screened.Trial registration: ClinicalTrials.gov identifier: NCT03464266..

Incidence of Herpes Simplex Virus Type 2 Infection Among African Women Using Depot Medroxyprogesterone Acetate, a Copper Intrauterine Device, or a Levonorgestrel Implant for Contraception: A Nested Randomized Trial.

BACKGROUND: Globally, women have higher herpes simplex virus type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM). METHODS: Within a randomized trial of the effect of 3 contraceptive methods-DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant-on human immunodeficiency virus (HIV) acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015 to 2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method. RESULTS: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI], .65-.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI, .71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI, .89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55; 95% CI, 2.78-4.48). CONCLUSIONS: In a randomized trial, we found no association between HSV-2 acquisition and use of 3 contraceptive methods. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02550067.

Patient characteristics associated with conversion from negative to positive severe acute respiratory syndrome coronavirus-2 polymerase chain reaction test results: Implications for clinical false-negativity from a single-center: A case-control study.

BACKGROUND: Accurate diagnosis of coronavirus disease 2019 is essential to limiting transmission within healthcare settings. The aim of this study was to identify patient demographic and clinical characteristics that could impact the clinical sensitivity of the nasopharyngeal severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) reverse transcription polymerase chain reaction (RT-PCR) test. METHODS: We conducted a retrospective, matched case-control study of patients who underwent repeated nasopharyngeal SARS-CoV2 RT-PCR testing at a tertiary care academic medical center between March 1 and July 23, 2020. The primary endpoint was conversion from negative to positive PCR status within 14 days. We conducted conditional logistic regression modeling to assess the associations between demographic and clinical features and conversion to test positivity. RESULTS: Of 51,116 patients with conclusive SARS-CoV2 nasopharyngeal RT-PCR results, 97 patients converted from negative to positive within 14 days. We matched those patients 1:2 to 194 controls by initial test date. In multivariate analysis, clinical suspicion for a respiratory infection (adjusted odds ratio [aOR] 20.9, 95% confidence interval [CI]: 3.1-141.2) and lack of pulmonary imaging (aOR 4.7, 95% CI: 1.03-21.8) were associated with conversion, while a lower burden of comorbidities trended toward an increased odds of conversion (aOR 2.2, 95% CI: 0.9-5.3). CONCLUSIONS: Symptoms consistent with a respiratory infection, especially in relatively healthy individuals, should raise concerns about a clinical false-negative result. We have identified several characteristics that should be considered when creating institutional infection prevention guidelines in the absence of more definitive data and should be included in future studies.

Urine Tenofovir Levels Measured Using a Novel Immunoassay Predict Human Immunodeficiency Virus Protection.

New tools are needed to support pre-exposure prophylaxis (PrEP) adherence for human immunodeficiency virus (HIV) prevention, including those that enable real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured using a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.

No Evidence of Sexual Risk Compensation Following PrEP Initiation Among Heterosexual HIV Serodiscordant Couples in Kenya and Uganda.

Recent studies among men who have sex with men suggest that sexual behaviors associated with risk of sexually transmitted infections increase following initiation of pre-exposure prophylaxis (PrEP) for HIV prevention. We used longitudinal data from HIV-uninfected participants (n = 1013) enrolled in an open-label study of PrEP delivered to Ugandan and Kenyan heterosexual HIV serodiscordant couples to understand the association between PrEP initiation and HIV risk-related sexual behaviors among these couples. In the month following PrEP initiation, the mean number of monthly sex acts within couples decreased from 7.9 to 6.9 (mean difference: - 1.1; 95% CI - 1.5, - 0.7) and the proportion of couples having condomless sex decreased from 65% to 32% (percentage point change: - 33%; 95% CI - 37%, - 30%); these behaviors then remained relatively constant over 2 years. We found no evidence of sexual risk compensation following PrEP initiation within African serodiscordant couples. However, roughly a third of couples continued to engage in condomless sex during follow up, emphasizing the importance of continued PrEP use to sustain HIV protection.

Factors Related to Incomplete Adherence to Antiretroviral Therapy among Adolescents Attending Three HIV Clinics in the Copperbelt, Zambia.

Little is known about adherence to antiretroviral therapy (ART) among adolescents in sub-Saharan Africa, where the majority of the world's HIV-positive adolescents reside. We assessed individual, household, and HIV self-management characteristics associated with a 48-hour treatment gap in the preceding 3 months, and a pharmacy medication possession ratio (MPR) that assessed the number of ART pills dispensed divided by the number of ART pills required in the past 6 months, among 285 Zambians, ages 15-19 years. Factors significantly associated with a 48-hour treatment gap were being male, not everyone at home being aware of the adolescent's HIV status, and alcohol use in the past month. Factors associated with an MPR < 90% included attending the clinic alone, alcohol use in the past month, and currently not being in school. Findings support programs to strengthen adolescents' HIV management skills with attention to alcohol use, family engagement, and the challenges adolescents face transitioning into adulthood, especially when they are no longer in school.

Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.

BACKGROUND: Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. METHODS AND FINDINGS: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship. CONCLUSIONS: This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.

Elucidating Pathways Mediating the Relationship Between Male Sex and COVID-19 Severity.

PURPOSE: To examine associations between male sex and SARS-CoV-2 test positivity, severe COVID-19 disease, and death in a single-site cohort, and assess whether male sex impacts risk for severe COVID-19 disease through socioeconomic status (SES), comorbidities, or inflammation. MATERIALS AND METHODS: We conducted a retrospective cohort study with data collected from University of Washington Medicine EMR from March 1 to September 29, 2020. All persons, regardless of age, were included if they had a conclusive diagnostic COVID-19 PCR test result. Our exposure was sex assigned at birth. We used Poisson regression to assess associations between sex and COVID-19 test positivity, disease severity and COVID-19 related death, and linear regression to compare viral cycle threshold at the first positive test. We conducted mediation analyses to assess interventional indirect effects of male sex on severe COVID-19 risk through socioeconomic status (SES, based on area deprivation and insurance type), comorbidities, and inflammation status. Models controlled for age and race/ethnicity. RESULTS: Of 32,919 males and 34,733 females included, 1469 (4.5%) and 1372 (4.0%) tested positive for SARS-CoV-2, respectively. Males were 14% more likely to test positive (RR = 1.14; 95% CI: 1.06-1.23), had 80% higher risk for severe COVID-19 disease (RR = 1.80; 95% CI: 1.39-2.33) and had 58% higher risk for death (RR = 1.58; 95% CI: 1.10-2.26) compared to females after adjusting for age and race/ethnicity. Mediation analyses indicated non-significant interventional indirect effects of male sex on severe COVID-19 disease through elevated inflammatory markers, SES and comorbidities, but the greatest effect was through the inflammation pathway. CONCLUSION: Males appear to be at higher risk at all steps of the continuum of COVID-19 illness. The strongest mediating signal, albeit non-significant, is with inflammatory pathways. Further elucidation of causal pathways linking sex and COVID-19 severity is needed in larger cohorts.

Contraceptive implant use duration is not associated with breakthrough pregnancy among women living with HIV and using efavirenz: a retrospective, longitudinal analysis.

INTRODUCTION: Contraceptive implants containing etonogestrel and levonorgestrel have emerged as popular contraceptive options among women in areas of high HIV burden in sub-Saharan Africa. However, recent pharmacokinetic data have shown drug-drug interactions between implants and efavirenz-containing antiretroviral therapy (ART), reducing the effectiveness of the implants. Here, we evaluated pregnancy incidence in 6-month intervals following implant initiation among women using efavirenz and contraceptive implants to assess whether the risk of breakthrough pregnancy is higher after specific periods of implant use. METHODS: We used data from a retrospective longitudinal analysis of women living with HIV ages 18-45 years in western Kenya who attended HIV-care facilities between 2011 and 2015. We used Cox proportional hazard models to compute hazard ratios (HRs) for breakthrough pregnancy by implant type and ART regimen. Depending on the model, we adjusted for socio-demographic and clinical factors, programme, site and interaction between calendar time and ART regimen. We utilized inverse probability weights (IPWs) to account for three sampling phases (electronic medical record [EMR], chart review and phone interview) and calculated overall parameter estimates. RESULTS: Women contributed 14,768 woman-years from the largest sampling phase (EMR). The median age was 31 years. Women used etonogestrel implants for 26-69% of the time and levonorgestrel implants for 7-31% of the time, depending on the sampling phase. Women used efavirenz, nevirapine or no ART for 27-33%, 40-46% and 15-26% of follow-ups, respectively. When combining sampling phases, there was little evidence to suggest that the relative hazard of pregnancy among efavirenz-containing ART users relative to nevirapine-containing ART changed with length of time on implants: IPW-adjusted HR of 3.1 (CI: [1.5; 6.4]) at 12 months, 3.4 (CI: [1.8; 6.3]) at 24 months, 3.8 (CI: [1.9; 7.7]) at 36 months and 4.2 (CI: [1.6; 11.1]) at 48 months (interaction p-value = 0.88). Similarly, no significant change in HRs over time was found when comparing women not using ART to nevirapine-containing ART users (interaction p-value = 0.49). CONCLUSIONS: We did not find evidence to suggest implants being more fallible from drug-drug interactions with efavirenz at later time intervals of implant use. Thus, we would not recommend shortening the duration of implant use or replacing implants sooner when concomitantly used with efavirenz.

Cost-effectiveness of adjuvanted versus nonadjuvanted influenza vaccine in adult hemodialysis patients.

BACKGROUND: Currently more than 340,000 individuals are receiving long-term hemodialysis (HD) therapy for end-stage renal disease and therefore are particularly vulnerable to influenza, prone to more severe influenza outcomes, and less likely to achieve seroprotection from standard influenza vaccines. Influenza vaccine adjuvants, chemical or biologic compounds added to a vaccine to boost the elicited immunologic response, may help overcome this problem. STUDY DESIGN: Economic stochastic decision analytic simulation model. SETTING & PARTICIPANTS: US adult HD population. MODEL, PERSPECTIVE, & TIMEFRAME: The model simulated the decision to use either an adjuvanted or nonadjuvanted vaccine, assumed the societal perspective, and represented a single influenza season, or 1 year. INTERVENTION: Adjuvanted influenza vaccine at different adjuvant costs and efficacies. Sensitivity analyses explored the impact of varying influenza clinical attack rate, influenza hospitalization rate, and influenza-related mortality. OUTCOMES: Incremental cost-effectiveness ratio of adjuvanted influenza vaccine (vs nonadjuvanted) with effectiveness measured in quality-adjusted life-years. RESULTS: Adjuvanted influenza vaccine would be cost-effective (incremental cost-effectiveness ratio <$50,000/quality-adjusted life-year) at a $1 adjuvant cost (on top of the standard vaccine cost) when adjuvant efficacy (in overcoming the difference between influenza vaccine response in HD patients and healthy adults) ≥60% and economically dominant (provides both cost savings and health benefits) when the $1 adjuvant's efficacy is 100%. A $2 adjuvant would be cost-effective if adjuvant efficacy was 100%. LIMITATIONS: All models are simplifications of real life and cannot capture all possible factors and outcomes. CONCLUSIONS: Adjuvanted influenza vaccine with adjuvant cost ≤$2 could be a cost-effective strategy in a standard influenza season depending on the potency of the adjuvant.

Safety review of tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis for pregnant women at risk of HIV infection.

Introduction: Pregnancy is a period of elevated HIV risk in high-burden settings, motivating the need for prevention tools that are both safe for use and effective during pregnancy. Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) is recommended by the World Health Organization, including for pregnant and postpartum women at substantial risk of HIV infection. Although TDF use during pregnancy appears generally safe, data on PrEP use during pregnancy remain limited.Areas covered: We provide an overview of the clinical pharmacology and efficacy of daily TDF-based PrEP and summarize current evidence on the safety of PrEP use by pregnant HIV-uninfected women. We synthesize relevant studies assessing pregnancy outcomes among pregnant women who are living with HIV (WLHIV) and using TDF-based therapy. Finally, we make comparison to the safety profiles of other emerging HIV prevention options.Expert opinion: The current evidence indicates that TDF/FTC PrEP use is not associated with increased risk of adverse pregnancy and early infant growth outcomes. While safety data are generally reassuring, there is need for continued accrual of data on growth and pregnancy outcomes in PrEP research, implementation projects, and controlled pharmacokinetic studies to support current evidence and to understand concentration-efficacy relationship in pregnant women.

Sexual Behaviors After PrEP Discontinuation Among HIV Serodiscordant Couples in Kenya and Uganda.

BACKGROUND: A strategy of pre-exposure prophylaxis (PrEP) transitioning to treatment as prevention is highly efficacious and cost effective for prevention of HIV transmission within HIV serodiscordant couples. We assessed whether couples who adopted this strategy experienced changes in sexual behaviors after HIV-negative partners discontinued PrEP and transitioned to rely primarily on their partner's adherence to antiretroviral therapy (ART) for prevention. SETTING: Kenya and Uganda. METHODS: Data are from the Partners Demonstration Project, a prospective, open-label evaluation of PrEP and ART use for HIV prevention. Using zero-inflated negative binomial models, we assessed changes in the level (ie, intercept) and trend over time (ie, slope) in total and condomless sex acts reported after PrEP discontinuation by HIV-negative partners. We conducted subgroup analyses based on HIV-negative partners' age and sex. RESULTS: We included 567 couples where the HIV-negative partner discontinued PrEP because of their partner with HIV using ART for ≥6 months. HIV-negative partners were women in 32.6% of couples and had a median age of 30 years. We observed no change in the level or trend over time in total sex acts [level adjusted rate ratio (aRR) = 0.95, 95% confidence interval (CI): 0.87 to 1.04; trend aRR = 1.00, 95% CI: 0.99 to 1.01] or condomless sex acts (level aRR = 0.97, 95% CI: 0.81 to 1.17; trend aRR = 1.00, 95% CI: 0.98 to 1.03) reported after PrEP discontinuation versus prediscontinuation. No significant changes in behaviors were observed in age and sex subgroups. CONCLUSIONS: PrEP discontinuation seems to result in no significant changes in couples' sexual behaviors. These data further support a strategy of time-limited PrEP use by serodiscordant couples.

Brief Report: High Accuracy of a Real-Time Urine Antibody-Based Tenofovir Point-of-Care Test Compared With Laboratory-Based ELISA in Diverse Populations.

BACKGROUND: Therapeutic drug monitoring measures antiretroviral adherence more accurately than self-report but has not been available at the point-of-care (POC) until now. We compare a novel POC test for urine tenofovir to laboratory-based enzyme-linked immunosorbent assay (ELISA) testing in diverse patient populations urine pre-exposure prophylaxis (PrEP). SETTING: Urine samples were analyzed using ELISA and the POC lateral flow immunoassay (LFA) test from 2 cohorts of PrEP users taking tenofovir disoproxil fumarate/emtricitabine: the Partners PrEP Study, which recruited Kenyan and Ugandan heterosexual men and women, and the IBrEATHe Study, which recruited US transgender women and men using gender-affirming hormone therapy. METHODS: We calculated the sensitivity, specificity, and accuracy of the POC test compared with ELISA at a cutoff of 1500 ng/mL. RESULTS: Overall, 684 urine samples were tested from 324 participants in the 2 cohorts. In Partners PrEP, 454 samples from 278 participants (41% women) were tested with a median age of 33 years. In IBrEATHe, 231 samples from 46 individuals (50% transwomen) were tested with a median age of 31 years. Comparison of the LFA read-out to ELISA yielded 100% sensitivity [97.5% one-sided confidence interval (CI) = 99.3%], 98.3% specificity (95% CI = 95.2% to 99.7%), and 99.6% accuracy (95% CI = 98.7% to 99.9%). CONCLUSION: The sensitivity, specificity, and accuracy of a novel POC test for urine tenofovir all exceeded 98% when compared with a laboratory-based ELISA method when tested in diverse patient populations. Given the LFA's high accuracy and expected low cost, this POC test is a promising tool to support antiretroviral adherence that could be widely scalable to real-world clinical settings.

HIV risk associated with serum medroxyprogesterone acetate levels among women in East and southern Africa.

BACKGROUND: Some observational studies have found increased HIV risk associated with self-reported use of injectable depot medroxyprogesterone acetate. Testing blood samples for medroxyprogesterone acetate (MPA), the progestin in depot medroxyprogesterone acetate, permits validation of self-reported data, and exploration of whether potential HIV risk is correlated with MPA levels, which are highest soon after injection. METHODS: We conducted a case-control study testing archived serum from women who participated in three longitudinal studies of HIV prevention in East and southern Africa. Case samples, from women who acquired HIV, were from visits that occurred at or immediately prior to the first evidence of HIV infection. Secondary analyses restricted to case samples collected within 15 and 30 days of the estimated date of HIV infection. Matched control samples were from women who remained HIV uninfected. We used multivariable conditional logistic regression to compare exogenous hormone levels, quantified through mass spectrometry, among cases and controls. RESULTS: When restricted to cases with samples collected within 15 days or less of estimated date of HIV infection, MPA detection was more frequent among women who acquired HIV (adjusted odds ratio = 2.75, 95% confidence interval 1.22-6.19). In this subset, the increase in HIV risk was only among samples with MPA detected at a low level of 0.02-0.50 ng/ml: 36.7% of cases and 9.4% of controls, adjusted odds ratio = 6.03, 95% confidence interval 2.50-14.54. CONCLUSION: Detection of MPA at low levels close to the estimated time of HIV acquisition was significantly more frequent among women who acquired HIV. Studies are needed that explore biological mechanisms elicited by any MPA level and HIV risk.

A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda.

OBJECTIVES: To evaluate pharmacokinetics and pharmacogenetics of contraceptive implant progestin concentrations in HIV-positive women initiating efavirenz (EFV)-containing or nevirapine (NVP)-containing antiretroviral therapy (ART). DESIGN: We analyzed stored samples from women self-reporting implant use in the Partners PrEP Study. METHODS: Plasma samples collected every 6 months were analyzed for levonorgestrel and etonogestrel concentrations. Progestin concentrations from samples collected after ART initiation were compared with pre-ART concentrations for intraindividual comparisons. We used adjusted linear mixed models to compare hormone concentrations between individuals on EFV and NVP to a no ART group. We then evaluated whether possessing certain alleles with known or possible influences on EFV, NVP, or progestin metabolism were associated with changes in progestin concentrations or modified the association between ART use and progestin concentrations. RESULTS: Our analysis included 11 women who initiated EFV, 13 who initiated NVP, and 36 who remained ART-naive. In the EFV group, the adjusted geometric mean ratio (aGMR) of levonorgestrel was 0.39 [90% confidence intervals (0.31, 0.49); P < 0.001] and the etonogestrel aGMR was 0.51 (0.34, 0.76; P = 0.006) compared with the control group. No difference was observed in the NVP group compared with controls [levonorgestrel 0.93 (0.74, 1.18); P = 0.64; etonogestrel 1.07 (0.77, 1.50); P = 0.73]. Possession of four allele variants were found to result in further reductions in progestin concentrations among those receiving EFV. CONCLUSION: Concomitant use of EFV significantly reduces levonorgestrel or etonogestrel concentrations by 61 and 49%, respectively, compared with no ART use. We also report allelic variants in hepatic enzymes that influenced the extent of the observed drug-interaction between progestins and EFV.

Adolescents living with HIV in the Copperbelt Province of Zambia: Their reproductive health needs and experiences.

BACKGROUND: Understanding and meeting the reproductive health needs of adolescents living with HIV (ALHIV) is a growing concern since advances in antiretroviral therapy mean that many ALHIV are now living into adulthood and starting to have sex. METHODS: We conducted a mixed-methods study in the Copperbelt Province of Zambia to advance our understanding of the reproductive health needs of ALHIV and to assess the extent to which these needs are being met. We conducted in-depth interviews (IDIs) with 32 ALHIV from two HIV clinics, 23 with their caregivers, and 10 with clinic staff. ALHIV were interviewed twice. We used the data from the qualitative interviews to create a cross-sectional survey that we conducted with 312 ALHIV in three HIV clinics. FINDINGS: The vast majority of ALHIV reported they wanted to have children in the future but lacked knowledge about preventing mother-to-child transmission. Some sexually active adolescents used condoms, although they wanted more information about and access to non-condom methods. Many ALHIV reported that their first sexual encounters were forced. Religious beliefs prevented some caregivers from discussing premarital sex and contraception with ALHIV. Clinic staff and caregivers had mixed views about integrating contraceptive counseling and method provision into HIV care and treatment services. Few sexually active ALHIV reported that they disclosed their HIV status to their sexual partners and few reported that they knew their sexual partner's status. CONCLUSIONS: ALHIV are in dire need of comprehensive sexual and reproductive health services and information including a range of contraceptive methods to prevent pregnancy, knowledge about preventing mother-to-child transmission and having a healthy pregnancy, skills related to HIV disclosure and condom negotiation to prevent horizontal transmission, and screening for sexual violence for both males and females if services are available.