Challenges, risks, and opportunities of antiretroviral drugs in women of reproductive potential.

INTRODUCTION: The HIV/AIDS epidemic has been one of the greatest challenges in global health, significantly affecting women of reproductive potential. Considerable advances in antiretroviral therapy for women living with HIV have contributed to improvements in quality of life, better reproductive and birth outcomes, and a reduced risk of perinatal transmission. AREAS COVERED: Despite the progress made, persistent challenges in access and adherence to antiretroviral drugs may limit their benefits for some women. More pharmacokinetic and safety studies in pregnant and lactating women are urgently needed, as are prospective surveillance systems to evaluate associations between fetal and infant antiretroviral exposures, drug-drug interactions, and pregnancy outcomes. EXPERT OPINION: Multipurpose technologies, such as combined HIV and other STI or unintended pregnancy prevention, and innovative delivery methods, such as the development of long-acting antiretrovirals, have the potential to reduce adherence challenges and enhance quality of life for women with HIV. Parallel advances in drug safety testing and surveillance are needed to ensure the health and safety of women with or at risk for HIV and children at risk for perinatal transmission.

Prevented perinatal HIV infections in the era of antiretroviral prophylaxis and treatment, United States, 1994-2020.

OBJECTIVE: The primary aim of this serial cross-sectional analysis is to estimate the total number of prevented perinatal HIV transmissions from the time of the initial recommendation for perinatal zidovudine (ZDV) prophylaxis in 1994 through 2020 in the US. METHODS: The estimated number of prevented transmissions was calculated as annual differences between expected and observed numbers of perinatal HIV transmissions. Annual expected number of transmissions was estimated by multiplying the annual number of births to women with HIV by 0.2255 (22.55%), i.e., the transmission rate of the control group in the ACTG Protocol 076 trial. We used published point estimates or, if only ranges were given, the midpoints of those ranges as the best estimates of the annual numbers of births to women with HIV and infants with perinatal HIV. When data were not available, we linearly interpolated or extrapolated the available data to obtain estimated numbers for each year. RESULTS: Between 1978 and 2020, the approximate number of live births to women with HIV was 191 267 (95% confidence interval [CI] 190 392-192 110) and for infants with diagnosed perinatal HIV, it was 21 379 (95% CI 21 088-21 695). Since 1994, the annual number of infants born with HIV decreased from 1263 (95% CI 1194-1333) to 33 in 2019 (95% CI 22-45) and 36 in 2020 (95% CI 25-48), corresponding to a 97% reduction. Cumulatively, an estimated total of 22 732 (95% CI 21 340-24 462) perinatal HIV infections were prevented from 1994 through to 2020. CONCLUSION: The elimination of perinatal HIV transmission-accompanied by the cumulative number of prevented cases exceeding that of perinatal HIV infections-is a major public health achievement in the US.

HIV Preexposure Prophylaxis Provision among Adolescents: 2018 to 2021.

BACKGROUND AND OBJECTIVES: HIV preexposure prophylaxis (PrEP) is safe, effective, and was approved for adolescents in 2018. Adolescents and young adults make up 20% of HIV diagnoses in the United States. Our objective was to describe trends in adolescents prescribed PrEP during 2018 through 2021 and characteristics of these adolescents and their PrEP providers. METHODS: We identified adolescents aged 13 to 19 years with oral PrEP prescriptions during 2018 through 2021 in a national pharmacy database using a validated algorithm. We assessed trends by calculating the overall percentage change and estimated annual percentage change with 95% confidence intervals. We described characteristics of adolescents and their PrEP providers in 2021. We performed χ2 analyses to assess differences by sex and age group. RESULTS: The number of adolescents prescribed PrEP increased 76.2% from 2018 to 2021 (estimated annual percentage change: 18.0% [95% confidence interval: 16.6-19.5]), despite decreases in 2020. We observed increases among all sex and age groups, with larger increases among older adolescents aged 18 to 19 years. The majority of the 6444 adolescents prescribed PrEP in 2021 were male (82.6%) and aged 18 to 19 years (87.8%). Among 2455 physician PrEP providers, 29.6% were pediatricians, with varying specialty distributions by adolescent age group (P < .001). Among the 217 pediatricians who prescribed PrEP to adolescents aged 13 to 17 years, 67.7% were general pediatricians. CONCLUSIONS: PrEP provision for adolescents has increased, largely among older and male adolescents. The availability of PrEP provides an important opportunity for pediatric providers to take an active role in HIV prevention.

Vaginal microbiome, antiretroviral concentrations, and HIV genital shedding in the setting of hormonal contraception initiation in Malawi.

OBJECTIVE: The aim of this study was to understand how vaginal microbiota composition affects antiretroviral concentrations in the setting of hormonal contraception initiation. METHODS: Cervicovaginal fluid (CVF) concentrations of tenofovir, lamivudine, and efavirenz from 73 Malawian women with HIV were compared before and after initiation of depot-medroxyprogesterone acetate (DMPA) or levonorgestrel implant. We evaluated antiretroviral concentrations and vaginal microbiota composition/structure in the context of contraception initiation and predicted genital shedding using multivariable repeated measurements models fit by generalized estimating equations. RESULTS: Mean lamivudine CVF concentrations decreased 37% 1 month after contraception initiation. Subgroup analyses revealed a 41% decrease in women 1 month after initiating levonorgestrel implant, but no significant difference was observed in DMPA group alone. Tenofovir, lamivudine, and efavirenz CVF concentrations were positively correlated with anaerobic bacteria associated with nonoptimal vaginal microbiota. Risk of genital HIV shedding was not significantly associated with tenofovir or lamivudine CVF concentrations [tenofovir relative risk (RR): 0.098, P = 0.75; lamivudine RR: 0.142, P = 0.54]. Lack of association between genital HIV shedding and efavirenz CVF concentrations did not change when adjusting for vaginal microbiota composition and lamivudine/tenofovir CVF concentrations (RR: 1.33, P = 0.531). CONCLUSION: No effect of hormone initiation on genital shedding provides confidence that women with HIV on either DMPA or levonorgestrel implant contraception will not have compromised ART efficacy. The unexpected positive correlation between antiretroviral CVF concentrations and certain bacterial taxa relative abundance requires further work to understand the mechanism and clinical relevance.

Dolutegravir and pregnancy outcomes including neural tube defects in the USA during 2008-20: a national cohort study.

BACKGROUND: A study from Botswana identified an increased risk of neural tube defects (NTDs) in infants of mothers with HIV who were treated with dolutegravir around the time of conception. We aimed to examine associations of dolutegravir use with NTDs and pregnancy loss using large health-care claims databases from the USA, a country with folic acid fortification of food. METHODS: In this cohort study, we analysed health-care claims data, recorded in the Merative MarketScan commercial database (MarketScan data) and Centers for Medicare & Medicaid Services Medicaid database (Medicaid data) from Jan 1, 2008, to Dec 31, 2020. We identified pregnancies with enrolment during their entire duration among women aged 15-49 years and we estimated time of conception. For each pregnancy, we determined HIV status and periconceptional exposure to dolutegravir or other antiretroviral agents. We estimated and compared the incidence rate of NTDs, stillbirths, and pregnancy loss (ie, spontaneous or induced abortions) by type of periconceptional antiretroviral exposure. We calculated adjusted risk ratios of the adverse outcomes using Poisson models adjusting for demographic and clinical factors. FINDINGS: Of 4 489 315 pregnancies in MarketScan data and 14 405 861 pregnancies in Medicaid data that had full enrolment, we identified 69 pregnancies in MarketScan data and 993 pregnancies in Medicaid data that were associated with HIV and periconceptional dolutegravir exposure. For women without HIV, the NTD rate was 4·1 per 10 000 live births (95% CI 3·9-4·3) in MarketScan and 5·7 per 10 000 live births (5·6-5·8) in Medicaid. No NTD cases were found among those with dolutegravir or non- dolutegravir antiretroviral drug exposure in the MarketScan data; only one NTD case was identified among women with dolutegravir, and three among women with non-dolutegravir antiretroviral exposure in Medicaid. After adjusting for covariates, there were no significant differences in risk ratios of NTD between groups with periconceptional dolutegravir or non-dolutegravir antiretroviral exposure and the group without HIV. However, compared with women without HIV, the risk of pregnancy loss was higher among women exposed to antiretroviral therapy: for dolutegravir exposure the adjusted risk ratio was 1·73 (95% CI 1·20-2·49) in MarketScan data and 1·41 (1·30-1·54) in Medicaid data; for non-dolutegravir antiretroviral exposure the adjusted risk ratio was 1·23 (1·10-1·37) in MarketScan data and 1·11 (1·07-1·15) in Medicaid data. INTERPRETATION: We studied the largest US cohort of women with periconceptional or early-pregnancy dolutegravir exposure. Our results do not show an increased risk of NTDs in exposed infants in the USA. Administrative databases can be used, with rigorous methodology, to study correlates of rare outcomes, such as NTDs, and to monitor for adverse pregnancy outcomes in women who receive antiretrovirals. FUNDING: US Centers for Disease Control and Prevention.

Achieving Elimination of Perinatal HIV in the United States.

ABSTRACT: In 2012, the Centers for Disease Control and Prevention published a Framework for Elimination of Perinatal Transmission of HIV in the United States in Pediatrics, setting the goals of an incidence of <1 case of perinatal HIV per 100 000 live births, and a perinatal transmission rate of <1%. We used National HIV Surveillance System data to monitor the numbers of perinatally acquired HIV cases among US-born persons and perinatal HIV diagnosis rates per 100 000 live births to approximate incidence. Perinatal HIV transmission rates from 2010 to 2019 were calculated by using estimates of live births to women with an HIV diagnosis from the National Inpatient Sample, Healthcare Cost and Utilization Project. The annual estimated number of live births to women with diagnosed HIV decreased from 4587 in 2010 to 3525 in 2019, and the number of US-born infants with perinatally acquired HIV decreased from 74 in 2010 to 32 in 2019. Annual perinatal HIV diagnosis rates declined from 1.9 to 0.9 per 100 000 live births, and perinatal HIV transmission rates declined from 1.6% to 0.9%. Racial and ethnic disparities in HIV diagnosis rates persisted but declined substantially over the 10-year period. Both diagnosis and transmission rate elimination goals were first achieved in 2019. To maintain the elimination of perinatal HIV, and to eliminate racial disparities, the continued coordinated effort of health care and public health is required. The approach to perinatal HIV elimination is a public health model that can be replicated or expanded to areas beyond HIV.

Identification of pregnancies and their outcomes in healthcare claims data, 2008-2019: An algorithm.

Pregnancy is a condition of broad interest across many medical and health services research domains, but one not easily identified in healthcare claims data. Our objective was to establish an algorithm to identify pregnant women and their pregnancies in claims data. We identified pregnancy-related diagnosis, procedure, and diagnosis-related group codes, accounting for the transition to International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis and procedure codes, in health encounter reporting on 10/1/2015. We selected women in Merative MarketScan commercial databases aged 15-49 years with pregnancy-related claims, and their infants, during 2008-2019. Pregnancies, pregnancy outcomes, and gestational ages were assigned using the constellation of service dates, code types, pregnancy outcomes, and linkage to infant records. We describe pregnancy outcomes and gestational ages, as well as maternal age, census region, and health plan type. In a sensitivity analysis, we compared our algorithm-assigned date of last menstrual period (LMP) to fertility procedure-based LMP (date of procedure + 14 days) among women with embryo transfer or insemination procedures. Among 5,812,699 identified pregnancies, most (77.9%) were livebirths, followed by spontaneous abortions (16.2%); 3,274,353 (72.2%) livebirths could be linked to infants. Most pregnancies were among women 25-34 years (59.1%), living in the South (39.1%) and Midwest (22.4%), with large employer-sponsored insurance (52.0%). Outcome distributions were similar across ICD-9 and ICD-10 eras, with some variation in gestational age distribution observed. Sensitivity analyses supported our algorithm's framework; algorithm- and fertility procedure-derived LMP estimates were within a week of each other (mean difference: -4 days [IQR: -13 to 6 days]; n = 107,870). We have developed an algorithm to identify pregnancies, their gestational age, and outcomes, across ICD-9 and ICD-10 eras using administrative data. This algorithm may be useful to reproductive health researchers investigating a broad range of pregnancy and infant outcomes.

An estimate of excess deaths among people with HIV during the coronavirus disease 2019 pandemic in the United States, 2020.

We developed an ad hoc method to estimate the number of excess deaths among persons with HIV (PWH) during the coronavirus disease 2019 (COVID-19) pandemic in the United States. Using this method, we estimated approximately 1448 excess deaths from COVID-19 among PWH in 2020 in the United States. We also developed an Excel workbook for use as a tool to quickly assess excess deaths among PWH in settings with limited surveillance data.

Influence of Hormonal Contraceptive Use and HIV on Cervicovaginal Cytokines and Microbiota in Malawi.

Important questions remain on how hormonal contraceptives alter the local immune environment and the microbiota in the female genital tract and how such effects may impact susceptibility to HIV infection. We leveraged samples from a previously conducted clinical trial of Malawian women with (n = 73) and without (n = 24) HIV infection randomized to depot medroxyprogesterone acetate (DMPA) or the levonogestrel implant in equal numbers within each group and determined the effects of these hormonal contraceptives (HCs) on the vaginal immune milieu and the composition of the vaginal microbiota. Longitudinal data for soluble immune mediators, measured by multiplex bead arrays and enzyme-linked immunosorbent assays (ELISAs), and vaginal microbiota, assessed by 16S rRNA gene amplicon, were collected prior to and over a period of 180 days post-HC initiation. DMPA and levonogestrel had only minimal effects on the vaginal immune milieu and microbiota. In women with HIV, with the caveat of a small sample size, there was an association between the median log10 change in the interleukin-12 (IL-12)/IL-10 ratio in vaginal fluid at day 180 post-HC compared to baseline when these women were classified as having a community state type (CST) IV vaginal microbiota and were randomized to DMPA. Long-lasting alterations in soluble immune markers or shifts in microbiota composition were not observed. Furthermore, women with HIV did not exhibit increased viral shedding in the genital tract after HC initiation. Consistent with the results of the ECHO (Evidence for Contraceptive Options and HIV Outcomes) trial, our data imply that the progestin-based HC DMPA and levonorgestrel are associated with minimal risk for women with HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT02103660). IMPORTANCE The results of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, the first large randomized controlled clinical trial comparing the HIV acquisition risk of women receiving DMPA, the levonorgestrel (LNG) implant, or the copper intrauterine device (IUD), did not reveal an increased risk of HIV acquisition for women on any of these three contraceptives. Our study results confirm that the two different progestin-based hormonal contraceptives DMPA and levonogestrel will not increase the risk for HIV infection. Furthermore, DMPA and levonogestrel have only minimal effects on the immune milieu and the microbiota in the vaginal tract, attesting to the safety of these hormonal contraceptives.

2gether: A Clinic-Based Intervention to Increase Dual Protection from Sexually Transmitted Infections and Pregnancy in Young African American Females.

Background: To determine whether the 2gether intervention increases use of a dual protection (DP; concurrent prevention of pregnancy and sexually transmitted infections [STIs]) strategy and decreases pregnancy and STIs among young African American females, who disproportionately experience these outcomes. Materials and Methods: We conducted a randomized clinical trial comparing the 2gether intervention to standard of care (SOC). Participants were self-identified African American females aged 14-19 years who were sexually active with a male partner in the past 6 months. Participants were followed for 12 months; 685 were included in the analytic sample. The primary biologic outcome was time to any incident biologic event (chlamydia, gonorrhea, trichomonas infections, or pregnancy). The primary behavioral outcomes were use of and adherence to a DP strategy. Results: 2gether intervention participants had a decreased hazard of chlamydia, gonorrhea, trichomonas infections, or pregnancy during follow-up, hazard ratio = 0.73 (95% confidence interval [CI] 0.58-0.92), and were more likely to report use of condoms plus contraception, generally, adjusted risk ratio (aRR) = 1.61 (95% CI 1.15-2.26) and condoms plus an implant or intrauterine device (IUD), specifically, aRR = 2.11 (95% CI 1.35-3.29) in the prior 3 months compared with those receiving SOC. 2gether participants were also more likely to report use of condoms plus an implant or IUD at last sex and consistently over the prior 3 months. Conclusions: 2gether was efficacious in increasing use of condoms with contraception and decreasing pregnancy or selected STIs in our participants. Implementation of this intervention in clinical settings serving young people with high rates of pregnancy and STIs may be beneficial. ClinicalTrials.gov, No. NCT02291224 (https://clinicaltrials.gov/ct2/show/NCT02291224?term=2gether&draw=2&rank=5).

Crush: A Randomized Trial to Evaluate the Impact of a Mobile Health App on Adolescent Sexual Health.

PURPOSE: Mobile technology allows delivery of sexual and reproductive health (SRH) information directly to youth. We tested the efficacy of Crush, a mobile application aimed at improving sexual health by promoting the use of SRH services and contraception among female adolescents. METHODS: We recruited 1,210 women aged 14-18 years through social media advertising and randomized them into a Crush intervention group and a control group that received a wellness app. At 3 and 6 months post randomization, we compared changes from baseline in behaviors, attitudes, self-efficacy, perceived social norms, birth control knowledge, perceived control and use intentions, and SRH service utilization. Odds ratios were estimated with multivariable logistic regression and adjusted for baseline outcome, age, race/ethnicity, mother's education, and sexual experience. RESULTS: There was no difference in accessing SRH services according to study group. Three months post baseline, Crush users had higher odds (p < .05) than control participants of reporting confidence in accessing SRH services (adjusted odds ratio [aOR] = 1.6, 95% confidence interval [CI]: 1.1-2.3) and of believing that it is a good thing to use birth control consistently (aOR = 2.3, 95% CI: 1.4-3.8). Six months after baseline, Crush users had higher odds than control participants of reporting they can control whether birth control is used every time they have sex (aOR = 1.8, 95% CI: 1.2-2.6) and perceiving they would get pregnant if they did not use birth control (aOR: 1.5, 95% CI: 1.1-2.2). Impacts on other behavioral constructs were also found. DISCUSSION: Crush was associated with improvements in knowledge, attitudes, and self-efficacy related to key SRH behaviors and may be a strategy to deliver SRH education to adolescent women. Studies including larger numbers of sexually active adolescents are needed to demonstrate behavioral impacts.

Decreased Human Immunodeficiency Virus Diagnosis Rates Among Black and Hispanic or Latino Men Who Have Sex With Men in US Jurisdictions Supported by the THRIVE Demonstration Project, 2014-2019.

BACKGROUND: Black and Hispanic/Latino men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV). In the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project, 7 community collaboratives were developed to provide comprehensive HIV prevention services for these populations. METHODS: We analyzed National HIV Surveillance System data to determine the number of HIV diagnoses for each year from 2014 to 2019 among Black, Hispanic/Latino, and White MSM in 7 THRIVE-eligible Metropolitan Statistical Areas (MSAs) that were awarded funding and 12 THRIVE-eligible MSAs that were not awarded funding. We used generalized linear Poisson regression models to estimate adjusted estimated annual percentage changes (EAPCs) with 95% confidence intervals for HIV diagnosis rates controlling for HIV prevalence, viral suppression, HIV testing rates, preexposure prophylaxis (PrEP) prescription rates, poverty, education, and insurance status. RESULTS: We found larger estimated decreases in HIV diagnosis rates in THRIVE jurisdictions compared with non-THRIVE jurisdictions. The adjusted EAPC among Black MSM was -8.2 (-11.7 to -4.6) in THRIVE MSAs compared with -4.2 (-7.8 to -0.4) in non-THRIVE MSAs. The adjusted EAPC among Hispanic/Latino MSM was -8.6 (-12.2 to -4.8) in THRIVE MSAs compared with -2.6 (-5.1 to -0.1)in non-THRIVE MSAs. The adjusted EAPC among White MSM was -7.6 (-12.0 to -3.1) in THRIVE MSAs compared with 5.9 (1.8-10.1) in non-THRIVE MSAs. CONCLUSIONS: The THRIVE community collaborative model was associated with a decrease in HIV diagnoses among Black and Hispanic/Latino MSM. To achieve the goals of the US Ending the HIV Epidemic initiative, effective interventions aimed to increase PrEP use need to be focused on Black and Hispanic/Latino MSM.

HIV Services and Outcomes During the COVID-19 Pandemic - United States, 2019-2021.

Increasing HIV testing, preexposure prophylaxis (PrEP), and antiretroviral therapy (ART) are pillars of the federal Ending the HIV Epidemic in the U.S. (EHE) initiative, with a goal of decreasing new HIV infections by 90% by 2030.* In response to the COVID-19 pandemic, a national emergency was declared in the United States on March 13, 2020, resulting in the closure of nonessential businesses and most nonemergency health care venues; stay-at-home orders also limited movement within communities (1). As unemployment increased during the pandemic (2), many persons lost employer-sponsored health insurance (3). HIV testing and PrEP prescriptions declined early in the COVID-19 pandemic (4-6); however, the full impact of the pandemic on use of HIV prevention and care services and HIV outcomes is not known. To assess changes in these measures during 2019-2021, quarterly data from two large U.S. commercial laboratories, the IQVIA Real World Data - Longitudinal Prescription Database (IQVIA),† and the National HIV Surveillance System (NHSS)§ were analyzed. During quarter 1 (Q1)¶ 2020, a total of 2,471,614 HIV tests were performed, 190,955 persons were prescribed PrEP, and 8,438 persons received a diagnosis of HIV infection. Decreases were observed during quarter 2 (Q2), with 1,682,578 HIV tests performed (32% decrease), 179,280 persons prescribed PrEP (6% decrease), and 6,228 persons receiving an HIV diagnosis (26% decrease). Partial rebounds were observed during quarter 3 (Q3), with 2,325,554 HIV tests performed, 184,320 persons prescribed PrEP, and 7,905 persons receiving an HIV diagnosis. The proportion of persons linked to HIV care, the number who were prescribed ART, and proportion with a suppressed viral load test (<200 copies of HIV RNA per mL) among those tested were stable during the study period. During public health emergencies, delivery of HIV services outside of traditional clinical settings or that use nonclinical delivery models are needed to facilitate access to HIV testing, ART, and PrEP, as well as to support adherence to ART and PrEP medications.

Impact of the coronavirus disease 2019 pandemic on prescriptions for antiretroviral drugs for HIV treatment in the United States, 2019-2021.

OBJECTIVE: To assess disruption in healthcare services for HIV treatment by national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic in the United States. DESIGN: Time-series analysis. METHODS: We analyzed the IQVIA Real World Data-Longitudinal Prescriptions Database and calculated time trends in the weekly number of persons with active antiretroviral prescriptions for HIV treatment, and of persons who obtained antiretroviral prescriptions during January 2017-March 2021. We used interrupted time-series models to estimate the impact of the COVID-19 pandemic on antiretroviral therapy (ART) use between March 2020 and March 2021. RESULTS: We found that the weekly number of persons with active antiretroviral prescriptions decreased by an average 2.5% (95% confidence interval [CI]: -3.8% to -1.1%), compared to predicted use, during March 2020 through March 2021. The weekly number of persons who obtained antiretroviral prescriptions decreased 4.5% (95% CI: -6.0% to -3.0%), compared to the predicted number. Men, persons aged ≤34 years, privately insured persons, and persons in medication assistance programs had greater decreases than other groups. CONCLUSIONS: We demonstrated a decrease in the number of persons with active antiretroviral prescriptions during the first year of the COVID-19 pandemic and the number did not return to levels expected in the absence of the pandemic. Disruptions in HIV care and decreased ART may lead to lower levels of viral suppression and immunologic control, and increased HIV transmission in the community.

U.S. Black Women and Human Immunodeficiency Virus Preexposure Prophylaxis Implementation.

Black women are disproportionately affected by the U.S. human immunodeficiency virus (HIV) epidemic. Preexposure prophylaxis (PrEP) is a safe and effective intervention for HIV prevention. Increased PrEP implementation is a pillar of the U.S. Department of Health and Human Services' Ending the HIV Epidemic in the U.S. initiative. However, PrEP has been used by a smaller proportion of women with PrEP indications compared with men. The goals of the Ending the HIV Epidemic in the U.S. initiative can be achieved only by increasing PrEP use among Black women. Obstetricians and gynecologists are uniquely poised to provide PrEP services for women. We describe the need for community-to-clinic models to overcome the barriers to PrEP use by Black women and a roadmap for clinician and community organization collaboration to increase access to and use of PrEP by Black women.

Antibody-dependent cellular cytotoxicity responses and susceptibility influence HIV-1 mother-to-child transmission.

HIV-1 vaccine efforts are primarily directed toward eliciting neutralizing antibodies (nAbs). However, vaccine trials and mother-to-child natural history cohort investigations indicate that antibody-dependent cellular cytotoxicity (ADCC), not nAbs, correlate with prevention. The ADCC characteristics associated with lack of HIV-1 acquisition remain unclear. Here, we examine ADCC and nAb properties in pretransmission plasma from HIV-1-exposed infants and from the corresponding transmitting and nontransmitting mothers' breast milk and plasma. Breadth and potency (BP) were assessed against a panel of heterologous, nonmaternal variants. ADCC and neutralization sensitivity were estimated for the strains in the infected mothers. Infants who eventually acquired HIV-1 and those who remained uninfected had similar pretransmission ADCCBP. Viruses circulating in the transmitting and nontransmitting mothers had similar ADCC susceptibility. Infants with higher pretransmission ADCCBP and exposure to more ADCC-susceptible strains were less likely to acquire HIV-1. In contrast, higher preexisting infant neutralization BP and greater maternal virus neutralization sensitivity did not associate with transmission. Infants had higher ADCCBP closer to birth and in the presence of high plasma IgG relative to IgA levels. Mothers with potent humoral responses against their autologous viruses harbored more ADCC-sensitive strains. ADCC sensitivity of the exposure variants and preexisting ADCCBP influenced mother-to-child HIV-1 transmission during breastfeeding. Vaccination strategies that enhance ADCC are likely insufficient to prevent HIV-1 transmission because some strains may have low ADCC susceptibility.

Impact of Coronavirus Disease 2019 (COVID-19) on Human Immunodeficiency Virus (HIV) Pre-exposure Prophylaxis Prescriptions in the United States-A Time-Series Analysis.

BACKGROUND: Uptake of HIV pre-exposure prophylaxis (PrEP) has been increasing in the United States since its FDA approval in 2012; however, the COVID-19 pandemic may have affected this trend. Our objective was to assess the impact of COVID-19 on PrEP prescriptions in the United States. METHODS: We analyzed data from a national pharmacy database from January 2017 through March 2021 to fit an interrupted time-series model that predicted PrEP prescriptions and new PrEP users had the pandemic not occurred. Observed PrEP prescriptions and new users were compared with those predicted by the model. Main outcomes were weekly numbers of PrEP prescriptions and new PrEP users based on a previously developed algorithm. The impact of the COVID-19 pandemic was quantified by computing rate ratios and percentage decreases between the observed and predicted counts during 15/3/2020-31/3/2021. RESULTS: In the absence of the pandemic, our model predicted that there would have been 1 058 162 PrEP prescriptions during 15/3/2020-31/3/2021. We observed 825 239 PrEP prescriptions, a 22.0% reduction (95% CI: 19.1-24.8%) after the emergency declaration. The model predicted 167 720 new PrEP users during the same period; we observed 125 793 new PrEP users, a 25.0% reduction (95% CI: 20.9-28.9%). The COVID-19 impact was greater among younger persons and those with commercial insurance. The impact of the pandemic varied markedly across states. CONCLUSIONS: The COVID-19 pandemic disrupted an increasing trend in PrEP prescriptions in the United States, highlighting the need for innovative interventions to maintain access to HIV-prevention services during similar emergencies.

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.

Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity.

In humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. Here, we evaluate antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1-exposed uninfected compared with HIV-1-exposed infected infants have higher ADCC and a combination of ADCC and nAb responses against their corresponding mother's strains. ADCC does not correlate with nAbs, suggesting they are independent activities. The infected infants with high ADCC compared with low ADCC, but not those with higher ADCC plus nAbs, have lower morbidity up to 1 year after birth. A higher IgA to IgG ratio, observed in BM supernatants and in a higher proportion of the infected compared with the uninfected infants, associates with lower ADCC. Against the exposure strains, ADCC, more than nAbs, associates with both lower mother-to-child transmission and decreased post-infection infant morbidity.