Differentiated Service Delivery Models for Maintaining HIV Treatment and Prevention Services During Crisis and Disease Outbreaks: Lessons from the COVID-19 Pandemic.

PURPOSE OF REVIEW: This review summarizes differentiated service delivery (DSD) models for HIV treatment and prevention that have been adapted for maintaining continuity of services during the COVID-19 pandemic and proposes strategies for sustaining their benefits now and during future disruptions. RECENT FINDINGS: The COVID-19 pandemic resulted in an overburdened and disrupted health system, forcing countries to adopt and/or scale up DSD models for HIV services. While initially implemented as emergency measures, these models evolved and were refined over time to fit recipient needs ensuring continued HIV treatment and prevention services with minimal health system impact. Successful models employed task shifting, community-based delivery models, multimonth scripting and dispensing, and telehealth for remote consultation. DSD models enabled HIV services globally to be maintained during the COVID-19 pandemic. Though these models and adaptations were critical in addressing health gaps and disruptions caused by the pandemic, they were beneficial in improving efficiency and access to client-centered services and should be sustained.

Behavioral Modeling and its Association with PrEP and ART Use in Ugandan HIV-Serodifferent Couples.

Integrating Pre-Exposure Prophylaxis (PrEP) delivery into Antiretroviral Therapy (ART) programs bridges the Human Immunodeficiency Virus (HIV) prevention gap for HIV-serodifferent couples prior to the partner living with HIV achieving viral suppression. Behavioral modeling is one mechanism that could explain health-related behavior among couples, including those using antiretroviral medications, but few tools exist to measure the extent to which behavior is modeled. Using a longitudinal observational design nested within a cluster randomized trial, this study examined the factor structure and assessed the internal consistency of a novel 24-item, four-point Likert-type scale to measure behavioral modeling and the association of behavioral modeling with medication-taking behaviors among heterosexual, cis-gender HIV-serodifferent couples. In 149 couples enrolled for research, a five-factor model provided the best statistical and conceptual fit, including attention to partner behavior, collective action, role modeling, motivation, and relationship quality. Behavioral modeling was associated with medication-taking behaviors among members of serodifferent couples. Partner modeling of ART/PrEP taking could be an important target for assessment and intervention in HIV prevention programs for HIV serodifferent couples.

The Effect of Stigma on Family Planning and HIV Pre-exposure Prophylaxis Decisions of Young Women Accessing Post-Abortion Care in Kenya.

Adolescent girls and young women (AGYW) in Eastern and Southern Africa face parallel epidemics of unintended pregnancy and HIV. Their sexual health decisions are often dominated by intersecting stigmas. In an implementation science project integrating delivery of daily, oral pre-exposure prophylaxis (PrEP) for HIV prevention into 14 post-abortion care (PAC) clinics in Kenya, we enrolled a subset of PrEP initiating AGYW (aged 15 to 30 years) into a research cohort. Utilizing log binomial models, we estimated the effect of PrEP stigma on PrEP continuation (measured via self-report and urine assay for tenofovir) and abortion stigma on contraceptive initiation. Between April 2022 and February 2023, 401 AGYW were enrolled after initiating PrEP through their PAC provider, of which 120 (29.9%) initiated highly-effective contraception. Overall, abortion and PrEP stigmas were high in this cohort. Abortion stigma was more prevalent among those that were adolescents, unmarried, and reported social harm. Among 114 AGYW returning for the month 1 follow-up visit, 83.5% reported continuing PrEP and 52.5% had tenofovir detected. In this subset, higher levels of PrEP stigma were significantly associated with greater likelihood of PrEP adherence, but not PrEP continuation. For abortion stigma, greater scores in the subdomain of isolation were significantly associated with greater likelihood of initiating a highly-effective contraception, while greater scores in the subdomain of community condemnation were significantly associated with reduced likelihood of initiating a highly-effective contraception. Given the burden of stigma documented by our work, PAC settings are a pivotal space to integrate stigma-informed counseling and to empower young women to optimize contraceptive and PrEP decisions.

Efficacy of the Dapivirine Vaginal Ring Accounting for Imperfect Adherence.

Product adherence is critical to obtaining objective estimates of efficacy of pre-exposure prophylactic interventions against HIV-1 infection. With imperfect adherence, intention-to-treat analyses assess the collective effects of complete, sub-optimal and non-adherence, providing a biased and attenuated estimate of the average causal effect of an intervention. Using data from the MTN-020/ASPIRE phase III trial evaluating HIV-1 efficacy of the dapivirine vaginal ring, we conducted per-protocol, and adherence-adjusted causal inference analyses using principal stratification and marginal structural models. We constructed two adherence cut offs of ≥ 0.9 mg (low cutoff) and > 4.0 mg (high cutoff) that represent drug released from the ring over a 28-day period. The HIV-1 efficacy estimate (95% CI) was 30.8% (3.6%, 50.3%) (P = 0.03) from the per-protocol analysis, and 53.6% (16.5%, 74.3%) (P = 0.01) among the highest predicted adherers from principal stratification analyses using the low cutoff. Marginal structural models produced efficacy estimates (95% CIs) ranging from 48.8 (21.8, 66.4) (P = 0.0019) to 56.5% (32.8%, 71.9%) (P = 0.0002). Application of adherence-adjusted causal inference methods are useful in interpreting HIV-1 efficacy in secondary analyses of PrEP clinical trials.

Systems analysis reveals differential expression of endocervical genes in African women randomized to DMPA-IM, LNG implant or cu-IUD.

Although effective contraceptives are crucial for preventing unintended pregnancies, evidence suggests that their use may perturb the female genital tract (FGT). A comparative analysis of the effects of the most common contraceptives on the FGT have not been evaluated in a randomized clinical trial setting. Here, we evaluated the effect of three long-acting contraceptive methods: depot medroxyprogesterone acetate(DMPA-IM), levonorgestrel(LNG) implant, and a copper intrauterine device (Cu-IUD), on the endocervical host transcriptome in 188 women from the Evidence for Contraceptive Options and HIV Outcomes Trial (ECHO) trial. Cu-IUD usage showed the most extensive transcriptomic changes, and was associated with inflammatory and anti-viral host responses. DMPA-IM usage was enriched for pathways associated with T cell responses. LNG implant had the mildest effect on endocervical gene expression, and was associated with growth factor signaling. These data provide a mechanistic basis for the diverse influence that varying contraceptives have on the FGT.

Awareness of Heightened Sexual and Behavioral Vulnerability as a Trigger for PrEP Resumption Among Adolescent Girls and Young Women in East and Southern Africa.

PURPOSE OF REVIEW: East and Southern Africa are the epicenter of the HIV epidemic. High HIV incidence rates among adolescent girls and young women (AGYW) remain stable over the last decade despite access to daily oral PrEP. Some settings have experienced high PrEP uptake among AGYW; however, discontinuation has been high. This review sought to understand drivers of PrEP discontinuation in this population in order to identify potential mechanisms to facilitate PrEP restart and optimize PrEP use. RECENT FINDINGS: Drivers of PrEP discontinuation included low perceived HIV acquisition risk, PrEP-associated side effects, pill burden, family/sexual partner disapproval, lack of/intermittent sexual activity, PrEP use stigma, fear of intimate partner violence, misinformation about long-term PrEP use, and limited/inconsistent access to PrEP. The most frequently reported driver of PrEP discontinuation was low perceived HIV acquisition risk. This indicates that innovative interventions to help AGYW recognize their HIV risk and make informed decisions about PrEP use are urgently needed.

Update on the Impact of Depot Medroxyprogesterone Acetate on Vaginal Mucosal Endpoints and Relevance to Sexually Transmitted Infections.

PURPOSE OF REVIEW: The long-acting reversible intramuscularly-injected contraceptive depot medroxyprogesterone acetate (DMPA-IM) is widely used by cisgender women in Africa. Although DMPA-IM provides reliable contraception, potential effects on the female genital tract (FGT) mucosa have raised concern, including risk of HIV infection. This review summarises and compares evidence from observational cohort studies and the randomised Evidence for Contraceptive Options in HIV Outcomes (ECHO) Trial. RECENT FINDINGS: Although previous observational studies found women using DMPA-IM had higher abundance of bacterial vaginosis (BV)-associated bacteria, increased inflammation, increased cervicovaginal HIV target cell density, and epithelial barrier damage, sub-studies of the ECHO Trial found no adverse changes in vaginal microbiome, inflammation, proteome, transcriptome, and risk of viral and bacterial STIs, other than an increase in Th17-like cells. Randomised data suggest that DMPA-IM use does not adversely change mucosal endpoints associated with acquisition of infections. These findings support the safe use of DMPA-IM in women at high risk of acquiring STIs, including HIV.

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.

How Central Ugandan HIV Clinics Adapted During COVID-19 Lockdown Restrictions to Promote Continuous Access to Care: A Qualitative Analysis.

We used qualitative data from the Partners PrEP Program (PPP) to address the question: How did Central Ugandan HIV clinics adapt to COVID-19 lockdown restrictions to promote continuous access to HIV care? PPP was a stepped-wedge cluster randomized trial of integrated PrEP and ART delivery for HIV serodifferent couples at Central Ugandan HIV clinics (NCT03586128). Individual interviews with purposefully selected PPP couples (N = 42) and clinicians, coordinators, and counselors providing HIV care (N = 36) were carried out. Sixty-four interviews were completed after lockdown and included questions about accessing and providing ART/PrEP refills during lockdown restrictions. We used an inductive, content-focused approach to analyze these interview data. Barriers to continuous access identified by interviewees included loss of income with increased cost of transport, reduced staff at clinics, and physical distancing at clinics. Interviewees pointed to multi-month refills, visits to clinics "close to home," transport to clinics for providers, and delivery of refills in neighborhoods as factors promoting continuous access to antiretroviral medications. Access barriers appeared somewhat different for ART and PrEP. Fewer resources for community delivery and pre-refill HIV testing requirements were identified as PrEP-specific access challenges. Participants emphasized their success in continuing ART/PrEP adherence during the lockdown, while providers emphasized missed refill visits. These results highlight the contributions of providers and ART/PrEP users to adaptation of HIV services during COVID-19 lockdown restrictions in Uganda. The roles of direct care providers and service users as drivers of adaptation should be recognized in future efforts to conceptualize and investigate health system resiliency.

Post-randomization Differences in Condomless Vaginal Sex Among Women Randomized to Intramuscular Depot Medroxyprogesterone Acetate Injections, a Copper Intrauterine Device or a Levonorgestrel Implant in the ECHO Trial.

The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. We evaluated post-randomization sexual behavior using an objective marker of condomless vaginal sex in a subset of participants. We conducted a sub-study among 458 ECHO participants at three sites (Cape Town, Johannesburg, Kisumu) to evaluate the frequency of condomless vaginal sex, measured by prostate specific antigen (PSA) detection in vaginal swabs, collected at the month 6 and final visit and the concordance of self-reported condomless vaginal sex with PSA detection, by randomized arm. We compared PSA detection frequency and concordance of PSA and self-reported condomless vaginal sex, by randomized group using Cochran-Mantel-Haenszel tests and adjusted generalized logistic growth curve models. PSA was detected less frequently in the DMPA-IM (16%), compared to the Cu-IUD (21%) and LNG implant (24%) groups, although results were not statistically significant in the unadjusted model when accounting for pre-specified multiple-testing criteria. There were significant differences in PSA detection between the DMPA-IM and LNG-implant groups (odds ratio 0.61 (95% CI 0.40, 0.94) in the adjusted model. There was moderate discordance between self-reported condomless vaginal sex and detection of PSA that was similar across randomized groups. These data suggest that women randomized to Cu-IUD and LNG implant may have had condomless sex more frequently than women randomized to DMPA-IM. The discordance between detectable PSA and self-reported sexual behaviour has important implications for design of future HIV prevention studies.

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..

Post-trial access to and use of pre-exposure prophylaxis in Durban, South Africa.

BACKGROUND: HIV endpoint-driven clinical trials increasingly provide oral pre-exposure prophylaxis (PrEP) as standard of prevention during the trial, however, among participants desiring to continue using PrEP at trial exit, little is known about post-trial PrEP access and continued use. METHODS: We conducted one-time, semi-structured, face-to-face, in-depth interviews with 13 women from Durban, South Africa, from November to December 2021. We interviewed women who initiated oral PrEP as part of the HIV prevention package during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial, elected to continue using PrEP at study exit, and were given a 3-month PrEP supply and referred to facilities for PrEP refills at the final trial visit. The interview guide probed for barriers and enablers to post-trial PrEP access, and current and future PrEP use. Interviews were audio-recorded and transcribed. Thematic analysis was facilitated using NVivo. RESULTS: Of the 13 women, six accessed oral PrEP post-trial exit, but five later discontinued. The remaining seven women did not access PrEP. Barriers to post-trial PrEP access and continued use included PrEP facilities having long queues, inconvenient operating hours, and being located far from women's homes. Some women were unable to afford transport costs to collect PrEP. Two women reported visiting their local clinics and requesting PrEP but were informed that PrEP was unavailable at the clinic. Only one woman was still using PrEP at the time of the interview. She reported that the PrEP facility was located close to her home, staff were friendly, and PrEP education and counselling were provided. Most women not on PrEP reported wanting to use it again, particularly if barriers to access could be alleviated and PrEP was easily available at facilities. CONCLUSIONS: We identified several barriers to post-trial PrEP access. Strategies to enhance PrEP access such as a reduction in waiting queues, convenient facility operating hours, and making PrEP more widely available and accessible are needed. It is also worth noting that oral PrEP access has expanded in South Africa from 2018 till now and this could improve access to PrEP for participants exiting trials who desire to continue PrEP.

Feasibility and acceptability of peer-delivered HIV self-testing and PrEP for young women in Kampala, Uganda.

BACKGROUND: Adolescent girls and young women (AGYW) account for 29% of new HIV infections in Uganda despite representing just 10% of the population. Peer support improves AGYW linkage to HIV care and medication adherence. We evaluated the feasibility and acceptability of peer delivered HIV self-tests (HIVST) and oral pre-exposure prophylaxis (PrEP) to young women in Uganda. METHODS: Between March and September 2021, we conducted a pilot study of 30 randomly selected young women, aged 18-24 years, who had received oral PrEP for at least three months, but had suboptimal adherence as measured by urine tenofovir testing (< 1500 ng/ml). Participants were offered daily oral PrEP and attended clinic visits three and six months after enrollment. Between clinic visits, participants were visited monthly by trained peers who delivered HIVST and PrEP. Feasibility and acceptability of peer-delivered PrEP and HIVST (intervention) were measured by comparing actual versus planned intervention delivery and product use. We conducted two focus groups with young women, and five in-depth interviews with peers and health workers to explore their experiences with intervention delivery. Qualitative data were analyzed using thematic analysis. RESULTS: At baseline, all 30 enrolled young women (median age 20 years) accepted peer-delivered PrEP and HIVST. Peer delivery visit completion was 97% (29/30) and 93% (28/30) at three and six months, respectively. The proportion of participants with detectable tenofovir in urine was 93% (27/29) and 57% (16/28) at months three and six, respectively. Four broad themes emerged from the qualitative data: (1) Positive experiences of peer delivered HIVST and PrEP; (2) The motivating effect of peer support; (3) Perceptions of female controlled HIVST and PrEP; and (4) Multi-level barriers to HIVST and PrEP use. Overall, peer delivery motivated young women to use HIVST and PrEP and encouraged persistence on PrEP by providing non-judgmental client-friendly services and adherence support. CONCLUSION: Peer delivery of HIVST and oral PrEP was feasible and acceptable to this sample of young women with suboptimal PrEP adherence in Uganda. Future larger controlled studies should evaluate its effectiveness among African AGWY.

"Gender-based Violence (GBV) and HIV, they are like sister and brother": barriers and facilitators to GBV screening and referral in public HIV treatment settings in Uganda.

BACKGROUND: People living with HIV are vulnerable to gender-based violence (GBV), which can negatively impact HIV treatment outcomes. National guidelines in Uganda recommend GBV screening alongside HIV treatment services. We explored barriers and facilitators to providers implementing GBV screening and referral in public antiretroviral therapy (ART) clinics in Uganda. METHODS: We conducted qualitative in-depth interviews. Providers were purposively sampled from 12 ART clinics to represent variation in clinical specialty and gender. We used the Theoretical Domains Framework to structure our deductive analysis. RESULTS: We conducted 30 in-depth interviews with providers implementing GBV screening and/or referral. Respondents had a median age of 36 (IQR: 30, 43) years and had been offering post-GBV care to clients for a median duration of 5 (4, 7) years. 67% of respondents identified as female and 57% were counselors. Facilitators of GBV screening and referral included providers having access to post-GBV standard operating procedures and screening tools, trainings offered by the Ministry of Health, facility-sponsored continuing medical education units and support from colleagues. Respondents indicated that referrals were uncommon, citing the following barriers: negative expectations regarding the quality and quantity of referral services; lack of financial resources to support clients, facilities, and referral partners throughout the referral process; and sociocultural factors that threatened client willingness to pursue post-GBV support services. CONCLUSIONS: Findings from this evaluation support the refinement of GBV screening and referral implementation strategies that leverage facilitators and address barriers to better support individuals living with HIV and who may have heightened vulnerability to GBV.

The Effect of Contraception on Genital Cytokines in Women Randomized to Copper Intrauterine Device, Depot Medroxyprogesterone Acetate, or Levonorgestrel Implant.

BACKGROUND: The ECHO trial randomized women to intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG-implant), or copper intrauterine device (Cu-IUD). In a substudy of the ECHO trial, we tested the hypothesis that contraceptives influence genital inflammation by comparing cervicovaginal cytokine changes following contraception initiation. In addition, we compared cytokine profiles in women who acquired HIV (cases) versus those remaining HIV negative (controls). METHODS: Women (n = 251) from South Africa and Kenya were included. Twenty-seven cervicovaginal cytokines were measured by Luminex at baseline, and 1 and 6 months after contraceptive iTanko et alnitiation. In addition, cytokines were measured preseroconversion in HIV cases (n = 25) and controls (n = 100). RESULTS: At 6 months after contraceptive initiation, women using Cu-IUD had increased concentrations of 25/27 cytokines compared to their respective baseline concentrations. In contrast, women initiating DMPA-IM and LNG-implant did not experience changes in cervicovaginal cytokines. Preseroconversion concentrations of IL-1ß, IL-6, and TNF-α, previously associated with HIV risk, correlated with increased HIV risk in a logistic regression analysis, although not significantly after correcting for multiple comparisons. Adjusting for contraceptive arm did not alter these results. CONCLUSIONS: Although Cu-IUD use broadly increased cervicovaginal cytokine concentrations at 6 months postinsertion, these inflammatory changes were found not to be a significant driver of HIV risk. CLINICAL TRIALS REGISTRATION: NCT02550067.

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.

Initiating Intramuscular Depot Medroxyprogesterone Acetate Increases Frequencies of Th17-like Human Immunodeficiency Virus Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial.

BACKGROUND: Cervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells. METHODS: Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry. RESULTS: Unlike the LNG implant or copper-IUD, DMPA-IM was associated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4ß7 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non-Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post-DMPA-IM (P = .03), although this did not influence barrier function. CONCLUSIONS: Our data suggest that DMPA-IM-driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity. CLINICAL TRIALS REGISTRATION: NCT02550067.

Vaginal microbiome-hormonal contraceptive interactions associate with the mucosal proteome and HIV acquisition.

Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24-11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44-2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.

HIV Prevention Tools Across the Pregnancy Continuum: What Works, What Does Not, and What Can We Do Differently?

PURPOSE OF REVIEW: Multiple tools exist to support the primary prevention of HIV in pregnant and postpartum women; however, there are opportunities to enhance their use and impact. This review summarizes the current status of HIV prevention tools and existing gaps and opportunities to improve their use along the pregnancy care continuum. RECENT FINDINGS: HIV screening efforts have steadily improved with close to universal screening of pregnant women in several East and Southern African countries. Strategies to implement partner testing through the distribution of HIV self-test kits are promising though linkage to care remains challenging. Syphilis screening rates are increasing though detection of other sexually transmitted infections could benefit from improved diagnostic capacity. Male and female condoms are rarely used and are often not the optimal tool of choice during pregnancy. Oral pre-exposure prophylaxis (PrEP) is a promising tool, although barriers such as the need for daily adherence, side effects, and stigma may limit its use. There is a growing pipeline of PrEP agents with alternative delivery platforms that might suit women's preferences better and supports the notion that choice is vital to improving HIV prevention coverage during the pregnancy-postpartum continuum. Clear guidance on which tools to use and how to use them, safety data supporting their use, and surveillance data documenting the scale and effectiveness of the tools will be imperative in establishing a path to more impactful prevention efforts among pregnant and postpartum women.

ART initiation among women newly diagnosed with HIV in a contraceptive trial in sub-Saharan Africa.

Current guidelines recommend starting antiretroviral therapy (ART) as soon as possible after HIV diagnosis to reduce morbidity, mortality and onward HIV transmission. We examined factors influencing ART initiation by women who seroconverted during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. ECHO, conducted between 2015 and 2018, enrolled HIV-negative, sexually active women, aged 16-35 years, from four African countries. Follow-up was 12-18 months, with quarterly HIV testing. Women with incident HIV infection received extensive counselling by trial staff and referral to local facilities for HIV care. Of 304 women with ≥90 days follow-up time since HIV diagnosis, 186(61.2%) initiated ART within 90 days, 69(22.7%) initiated after 90 days, and 49(16.1%) had not initiated by the end of the study. There were no statistically significant differences in characteristics among women who initiated ART ≤90 days versus those who did not. Frequent reasons for delayed or non-initiation of ART included not feeling ready to start ART and being newly diagnosed. In a large clinical trial, ART initiation was modest within 90 days of HIV diagnosis and grew to 84% with longer observation. Despite extensive counselling on the importance of early ART initiation, personal barriers delayed some women from starting ART.