Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women.

BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).

Drug concentrations in hair and dried blood spots as PrEP adherence metrics during pregnancy and postpartum.

We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV pre-exposure prophylaxis (PrEP) during pregnancy and postpartum and compared hair levels with tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). Overall, 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster randomized trial. Having a partner known to be living with HIV was associated with higher hair TFV levels (p<0.001). Hair TFV concentrations were strongly correlated with DBS TFV-DP levels (r=0.76, p<0.001), indicating hair as promising cumulative adherence metric for perinatal PrEP assessment.

Viral Suppression Trajectories Destabilized After Coronavirus Disease 2019 Among US People With Human Immunodeficiency Virus: An Interrupted Time Series Analysis.

We examined changes in the proportion of people with human immunodeficiency virus (PWH) with virologic suppression (VS) in a multisite US cohort before and since the coronavirus disease 2019 (COVID-19) pandemic. Overall, prior gains in VS slowed during COVID-19, with disproportionate impacts on Black PWH and PWH who inject drugs.

Interruptions in HIV and Behavioral Health Care for Criminal-Legal Involved People Living with HIV Following Implementation of Decarceration and Shelter in Place in San Francisco, California.

Decarceration policies, enacted for SARS-CoV-2 mitigation in carceral settings, potentially exacerbated barriers to care for people living with HIV (PWH) with criminal legal involvement (CLI) during Shelter-in-Place (SIP) by limiting opportunities for engagement in provisions of HIV and behavioral health care. We compared health care engagement for PWH with CLI in San Francisco, California before and after decarceration and SIP using interrupted time series analyses. Administrative data identified PWH booked at the San Francisco County Jail with at least one clinic encounter from 01/01/2018-03/31/2020 within the municipal health care network. Monthly proportions of HIV, substance use, psychiatric and acute care encounters before (05/01/2019-02/29/2020) and after (03/01/2020-12/31/2020) SIP and decarceration were compared using Generalized Estimating Equation (GEE) log-binomial and logistic regression models, clustering on the patient-level. Of 436 patients, mean age was 43 years (standard-deviation 11); 88% cisgender-male; 39% white, 66% homeless; 67% had trimorbidity by Elixhauser score (medical comorbidity, psychotic disorder or depression, and substance use disorder). Clinical encounters immediately dropped following SIP for HIV (aOR = 0.77; 95% CI: 0.67, 0.90) and substance use visits (aRR = 0.83; 95% CI: 0.70, 0.99) and declined in subsequent months. Differential reductions in clinical encounters were seen among Black/African Americans (aRR = 0.93; 95% CI: 0.88, 0.99) and people experiencing homelessness (aRR = 0.92; 95% CI: 0.87, 0.98). Significant reductions in care were observed for PWH with CLI during the COVID-19 pandemic, particularly among Black/African Americans and people experiencing homelessness. Strategies to End the HIV Epidemic must improve engagement across diverse care settings to improve outcomes for this key population.

Pandemic expertise: qualitative findings on the experiences of living with HIV during the COVID-19 pandemic.

This qualitative study explored the experiences of people living with HIV (PLWH) in the San Francisco Bay Area, United States, during the COVID-19 pandemic and subsequent public health restrictions at a safety net HIV clinic. Patients (N = 30) were recruited for Spanish/English language semi-structured interviews (n = 30), translated when necessary, and analyzed thematically. The recurring theme of "pandemic expertise" emerged from the data: skills and attitudes developed through living with HIV helped PLWH cope with the COVID-19 pandemic, including effective strategies for dealing with anxiety and depression; appreciation for life; and practical experience of changing behavior to protect their health. A subset did not consider living with HIV helped them adapt to the COVID-19 pandemic, with some describing their lives as chaotic due to housing issues and/or ongoing substance use. Overall, interviewees reported finding trustworthy health information that helped them follow COVID-19 prevention strategies. Although living with HIV is associated with a higher prevalence of mental health concerns, substance use, and stigma, these challenges can also contribute to increased self-efficacy, adaptation, and resilience. Addressing structural issues such as housing appears to be key to responding to both pandemics.

Demonstration Project of Long-Acting Antiretroviral Therapy in a Diverse Population of People With HIV.

BACKGROUND: Intramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables. OBJECTIVE: To examine LA-ART in a population of PWH that includes those with viremia. DESIGN: Observational cohort study. SETTING: Urban academic safety-net HIV clinic. PATIENTS: Publicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use. INTERVENTION: Demonstration project of long-acting injectable CAB-RPV. MEASUREMENTS: Descriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data. RESULTS: Between June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks. LIMITATION: Single-site study. CONCLUSION: This project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed. PRIMARY FUNDING SOURCE: National Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.

A Position Statement on Mpox as a Sexually Transmitted Disease.

The global outbreak of mpox virus constituted an international public health emergency. Reports have highlighted (1) a temporal association between sexual activity and mpox, (2) an association between specific sexual practices and location of lesion development, (3) a high frequency of sexual practices conferring risk for other sexually transmitted infections among cases of mpox, (4) that mpox virus can be isolated from sexual fluids, (4) that isolated virus is infectious, and (5) a high frequency of anogenital lesions prior to disease dissemination suggesting direct inoculation during sexual activities. Finally, a growing body of evidence suggests that sexual transmission is the predominant mode of transmission for mpox virus. We therefore conclude that mpox is a sexually transmitted disease. Labeling it as such will help focus public health interventions, such as vaccinations, testing, and treatment, as well as facilitate focused awareness and education programs toward behavioral modifications to reduce exposures.

Urine Tenofovir Levels Strongly Correlate With Virologic Suppression in Patients With Human Immunodeficiency Virus on Tenofovir Alafenamide-Based Antiretroviral Therapy.

We found that urine tenofovir (TFV) levels >1500 ng/mL strongly predict virologic suppression among people with human immunodeficiency virus taking tenofovir alafenamide (odds ratio, 5.66; 95% confidence interval, 1.59-20.14; P = .007). This suggests an existing point-of-care assay developed for tenofovir disoproxil fumarate will support adherence monitoring for patients on all TFV-based antiretrovirals.

First Demonstration Project of Long-Acting Injectable Antiretroviral Therapy for Persons With and Without Detectable Human Immunodeficiency Virus (HIV) Viremia in an Urban HIV Clinic.

BACKGROUND: Long-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naive or experienced people with human immunodeficiency virus (HIV; PWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART. METHODS: Ward 86 is a large HIV clinic in San Francisco that serves publicly insured and underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method. RESULTS: Between June 2021 and April 2022, 51 patients initiated LAI-ART, with 39 receiving at least 2 follow-up injections by database closure (median age, 46 years; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients who initiated injections with viral suppression (median CD4 cell count, 706 cells/mm3), 100% (95% confidence interval [CI], 86%-100%) maintained viral suppression. Of 15 patients who initiated injections with detectable viremia (median CD4 cell count, 99 cells/mm3; mean log10 viral load, 4.67; standard deviation, 1.16), 12 (80%; 95% CI, 55%-93%) achieved viral suppression, and the other 3 had a 2-log viral load decline by a median of 22 days. CONCLUSIONS: This small demonstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.

Contingency Management for Integrated Harm Reduction Among Men Who Have Sex with Men Who Use Methamphetamine in Los Angeles: A Pilot Assessment.

Methamphetamine (MA) use is associated with HIV transmission among men who have sex with men (MSM) and lapses in medication adherence. Contingency Management (CM) is effective in reducing MA use, but studies of CM to support adherence to HIV prevention or treatment are limited. We conducted a pilot trial of a CM intervention to reduce MA use and improve PrEP/ART adherence among MSM prescribed a tenofovir (TFV)-based regimen for HIV prevention or treatment. Participants were randomly assigned to receive escalating incentives for either MA abstinence or TFV adherence (based on point-of-care urine testing), and to a monitoring schedule of either 2 or 3 visits/week for 4 weeks. 19 MSM were randomized to either CM for MA use or CM for PrEP/ART adherence (median age: 38; IQR: 28-46) and 15 were living with HIV. Participants attended 95.7% (67/70) of scheduled visits in the 2x/week arm and 74.8% (74/99) in the 3x/week arm. TFV adherence was higher among participants in the TFV adherence arm with 93.5% (n = 72/77) of urine samples positive for TFV, compared to 76.6% (n = 49/64) in the MA abstinence arm (p = 0.007). Participants in the MA abstinence arm had more urine samples negative for MA metabolites (20.3%, n = 13/64) than those receiving CM for TFV adherence (6.5%, n = 5/77; p = 0.021). A CM model for MA abstinence and PrEP/ART adherence using twice-weekly visits and urine testing for MA and TFV for MSM who use MA is feasible and potentially effective as an integrated harm reduction strategy.

Perceptions and Experiences of Returning Self-collected Specimens for HIV, Bacterial STI and Potential PrEP Adherence Testing among Sexual Minority Men in the United States.

Few studies among gay, bisexual and other men who have sex with men (GBMSM) have examined facilitators and barriers to self-collecting specimens for extragenital STI screening, and none have evaluated attitudes towards self-collecting hair samples that can be utilized for PrEP drug level testing to assess adherence. To address this gap, we interviewed 25 sexually active GBMSM who were offered a choice to self-collect and return finger-stick blood samples (for actual HIV testing), pharyngeal swabs, rectal swabs and urine specimens (for actual gonorrhea and chlamydia testing), and hair samples (to visually determine their adequacy for PrEP drug level testing): 11 who returned all, 4 who returned some, and 10 who did not return any. Participants found self-collecting finger-stick blood samples and rectal swabs more challenging than other specimens. Frequently discussed facilitators of return included an opportunity to confirm one's HIV or STI status, limited access to a healthcare provider and a desire to advance research focusing on home-based testing. Commonly cited barriers to return included low self-efficacy pertaining to self-collection and apprehension around the possibility of delay or loss of specimens during transit. Offering additional support such as real-time video conferencing may prove helpful in future field-based research with GBMSM.

PrEPare for Work: A Pilot Randomized Controlled Trial of an Intervention to Optimize HIV PrEP Outcomes Among Male Sex Workers.

HIV pre-exposure prophylaxis (PrEP) use is limited among male sex workers, who are at exceptionally high-risk for HIV infection. We developed a theory-informed, two-pronged intervention ("PrEPare-for-Work") to optimize PrEP initiation and adherence among male sex workers, which was preliminarily evaluated in a two-stage pilot randomized controlled trial of 110 male sex workers in the US Northeast. Individuals randomized to the Stage 1 PrEPare-for-Work Case Management arm were three times as likely as those in the standard of care (SOC) arm to initiate PrEP (RR = 2.95, 95% CI = 1.57-5.57). Participants who initiated PrEP and were randomized to the Stage 2 PrEPare-for-Work Adherence Counseling arm had higher rates of prevention-effective adherence (measured via tenofovir in hair) compared to those in the SOC arm (RR = 1.7, 95% CI 0.64-4.77; 55.6% vs. 28.6%, respectively); though not statistically significant. Given the need and the promise of this pilot RCT, further efficacy testing is warranted and should be prioritized.

RESUMEN: El uso de la profilaxis prexposición (PrEP) para prevenir la adquisición del VIH es limitado entre trabajadores sexuales masculinos, que están en muy alto riesgo de contraerlo. Desarrollamos una intervención de dos partes basada en la teoría para optimizar el inicio y la observancia del tratamiento de la PrEP entre trabajadores sexuales masculinos, que se evaluó preliminarmente en un ensayo piloto controlado y aleatorizado (ECA) de dos fases de 110 trabajadores sexuales masculinos en el noreste de Estados Unidos. Las personas aleatorizadas al grupo de intervención (la primera fase de nuestro programa "PrEPare for Work" ­ la atención individualizada) eran tres veces más probable que las aleatorizadas al grupo control (la norma de atención) a iniciar la PrEP (RR = 2.95, 95% IC = 1.57­5.57). Los participantes que iniciaron la PrEP y se aleatorizaron al grupo de intervención (la segunda fase de "PrEPare for Work" ­ la terapia para aumentar la adherencia al tratamiento) tenían tasas más altas de adherencia al tratamiento (medido por tenofovir en el cabello) que los aleatorizados al grupo control (RR = 1.7, 95% IC 0.64­4.77; 55.6% vs. 28.6%, respectivamente); aunque la diferencia no fue estadísticamente significativa. En vista de la necesidad y el potencial de este ECA piloto, más pruebas de eficacia son necesarias y deben ser priorizadas.

Perspectives of people living with HIV and health workers about a point-of-care adherence assay: a qualitative study on acceptability.

Current antiretroviral therapy (ART) adherence monitoring is premised on patients' self-reported adherence behaviour (prone to recall error) and verified by blood viral load measurement (which can delay results). A newly developed Urine Tenofovir Rapid Assay (UTRA) assesses tenofovir in urine at point-of-care and is a novel tool to test and immediately respond to adherence levels of people living with HIV (PLHIV). We explored PLHIV and health workers' initial perceptions about integrating the UTRA into routine medical care for adherence support. We conducted a series of once-off in-depth qualitative interviews with PLHIV (n = 25) and health workers (n = 5) at a primary care health facility in Cape Town, South Africa. Data analysis involved descriptive summaries of key emergent themes with illustrative case examples. We applied a deductive, outcomes-driven analytic approach to the summaries using the Implementation Outcomes Framework proffered by Proctor et al. (2011). The three relevant concepts from this framework that guided our evaluation were: acceptability, appropriateness, and feasibility. We found positive perceptions about the UTRA from many PLHIV and health worker participants. Many PLHIV reported that the immediate results offered by the UTRA could enable them to have constructive discussions with health workers on how to resolve adherence challenges in real-time. Few PLHIV reported concerns that drinking alcohol could affect their UTRA results. Many health workers reported that the UTRA could help them identify patients at risk of treatment failure and immediately intervene through counselling, though some relayed that they would support the UTRA's implementation if more staff members could be added in their busy facility. Overall, these findings show that the UTRA was widely perceived to be acceptable and actionable by many PLHIV and health workers in the study.

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.

HIV Treatment Outcomes in POP-UP: Drop-in HIV Primary Care Model for People Experiencing Homelessness.

BACKGROUND: People with HIV experiencing homelessness have low rates of viral suppression, driven by sociostructural barriers and traditional care system limitations. Informed by the capability-opportunity-motivation-behavior (COM-B) model and patient preference research, we developed POP-UP, an integrated drop-in (nonappointment-based) HIV clinic with wrap-around services for persons with housing instability and viral nonsuppression in San Francisco. METHODS: We report HIV viral suppression (VS; <200 copies/mL), care engagement, and mortality at 12 months postenrollment. We used logistic regression to determine participant characteristics associated with VS. RESULTS: We enrolled 112 patients with viral nonsuppression and housing instability: 52% experiencing street-homelessness, 100% with a substance use disorder, and 70% with mental health diagnoses. At 12 months postenrollment, 70% had ≥1 visit each 4-month period, although 59% had a 90-day care gap; 44% had VS, 24% had viral nonsuppression, 23% missing, and 9% died (6 overdose, 2 AIDS-associated, 2 other). No baseline characteristics were associated with VS. CONCLUSIONS: The POP-UP low-barrier HIV care model successfully reached and retained some of our clinic's highest-risk patients. It was associated with VS improvement from 0% at baseline to 44% at 12 months among people with housing instability. Care gaps and high mortality from overdose remain major challenges to achieving optimal HIV treatment outcomes in this population.

Differences in Post-mRNA Vaccination Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Immunoglobulin G (IgG) Concentrations and Surrogate Virus Neutralization Test Response by Human Immunodeficiency Virus (HIV) Status and Type of Vaccine: A Matched Case-Control Observational Study.

Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination, people living with human immunodeficiency virus (HIV, PLWH) had lower surrogate virus neutralization test response (P = .03) and a trend toward lower immunoglobulin G (IgG) response (P = .08), particularly among those with lower CD4+ T-cell counts and who received the BNT162b2 vaccine. Study of the impact of supplemental vaccine doses among PLWH is needed.

Impact of Multicomponent Support Strategies on Human Immunodeficiency Virus Virologic Suppression Rates During Coronavirus Disease 2019: An Interrupted Time Series Analysis.

BACKGROUND: After coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline. METHODS: We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing. RESULTS: Data from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5). CONCLUSIONS: The VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

Impact of Tamoxifen on Vorinostat-Induced Human Immunodeficiency Virus Expression in Women on Antiretroviral Therapy: AIDS Clinical Trials Group A5366, The MOXIE Trial.

BACKGROUND: Biological sex and the estrogen receptor alpha (ESR1) modulate human immunodeficiency virus (HIV) activity. Few women have enrolled in clinical trials of latency reversal agents (LRAs); their effectiveness in women is unknown. We hypothesized that ESR1 antagonism would augment induction of HIV expression by the LRA vorinostat. METHODS: AIDS Clinical Trials Group A5366 enrolled 31 virologically suppressed, postmenopausal women on antiretroviral therapy. Participants were randomized 2:1 to receive tamoxifen (arm A, TAMOX/VOR) or observation (arm B, VOR) for 5 weeks followed by 2 doses of vorinostat. Primary end points were safety and the difference between arms in HIV RNA induction after vorinostat. Secondary analyses included histone 4 acetylation, HIV DNA, and plasma viremia by single copy assay (SCA). RESULTS: No significant adverse events were attributed to study treatments. Tamoxifen did not enhance vorinostat-induced HIV transcription (between-arm ratio, 0.8; 95% confidence interval [CI], .2-2.4). Vorinostat-induced HIV transcription was higher in participants with increases in H4Ac (fold increase, 2.78; 95% CI, 1.34-5.79) vs those 9 who did not (fold increase, 1.04; 95% CI, .25-4.29). HIV DNA and SCA plasma viremia did not substantially change. CONCLUSIONS: Tamoxifen did not augment vorinostat-induced HIV RNA expression in postmenopausal women. The modest latency reversal activity of vorinostat, postmenopausal status, and low level of HIV RNA expression near the limits of quantification limited assessment of the impact of tamoxifen. This study is the first HIV cure trial done exclusively in women and establishes both the feasibility and necessity of investigating novel HIV cure strategies in women living with HIV. CLINICAL TRIALS REGISTRATION: NCT03382834.

HIV and women in the USA: what we know and where to go from here.

New diagnoses of HIV infection have decreased among women in the USA overall, but marked racial and geographical disparities persist. The federal government has announced an initiative that aims to decrease the number of new infections in the nation by 90% within the next 10 years. With this in mind, we highlight important recent developments concerning HIV epidemiology, comorbidities, treatment, and prevention among women in the USA. We conclude that, to end the US HIV epidemic, substantially greater inclusion of US women in clinical research will be required, as will better prevention and treatment efforts, with universal access to health care and other supportive services that enable women to exercise agency in their own HIV prevention and care. Ending the epidemic will also require eliminating the race, class, and gender inequities, as well as the discrimination and structural violence, that have promoted and maintained the distribution of HIV in the USA, and that will, if unchecked, continue to fuel the epidemic in the future.