COVID-19 Vaccination Uptake, Infection Rates, and Seropositivity Among Youth Experiencing Homelessness in the United States.

BACKGROUND: People experiencing homelessness are at greater risk of exposure and poor health outcomes from COVID-19. Yet, little data exists on the prevalence and correlates of COVID-19 among homeless populations. To mitigate the spread and severity, uptake of the COVID-19 vaccine is needed. This can be challenging among youth experiencing homelessness who are more likely to be unvaccinated when compared to stably housed youth. OBJECTIVE: We conducted this study to determine the prevalence and correlates of COVID-19 among youth experiencing homelessness. METHODS: We examined experiences of COVID-19 symptoms, self-report of infection, rates of COVID-19 antibodies and distinguished between natural and vaccinated immunity among youth experiencing homelessness (N = 265) recruited in one large metropolitan area in the South. RESULTS: Based on self-report, very few participants experienced any symptoms, and 80% had never been diagnosed with COVID-19. Of those with COVID-19 antibodies (68%), the proportion with antibodies resulting from natural infection was 44%. The vaccination rate was 42%. Younger and vaccinated participants and those in shelters were likelier to have COVID-19 antibodies. Black and Hispanic youth were more likely than White youth to have had COVID-19. Those who adopted only one or two prevention behaviors were more likely to acquire a natural infection than those who adopted three or more prevention behaviors. DISCUSSION: Youth experiencing homelessness report low vaccination rates, disrupted access to health care and social supports, and underlying chronic conditions, which may explain why they face poorer outcomes when infected with COVID-19. Vaccination and risk mitigation strategies to combat the high prevalence of COVID-19 are especially needed for sheltered youth who are at high risk yet are often asymptomatic.

Lessons learned from conducting a community-based, nurse-led HIV prevention trial with youth experiencing homelessness: Pivots and pitfalls.

OBJECTIVE: This article highlights key lessons learned while conducting a nurse-led community-based HIV prevention trial with youth experiencing homelessness (YEH), focusing on sexually transmitted infections testing and treatment, intervention sessions, community partnerships, and participant recruitment and retention. DESIGN: The insights and experiences shared aim to inform future research and the design of interventions targeting populations at high risk, particularly when facing unanticipated challenges. By addressing these areas, the article contributes to the decision-making for the design and delivery of effective strategies to improve the health outcomes among marginalized populations. RESULTS: The findings underscore the importance of flexibility and active participant engagement, cultivating strong relationships with community partners, utilizing technology and social media, and fostering a diverse research team that represents the heterogeneity of youth experiencing homelessness across race/ethnicity, gender identity, sexual orientation, and lived experiences. CONCLUSIONS: These recommendations aim to enhance participant access, engagement, and retention, while promoting rigorous research and meaningful study outcomes for YEH.

Forty-Eight Week Outcomes of a Site-Randomized Trial of Combined Cognitive Behavioral Therapy and Medication Management Algorithm for Treatment of Depression Among Youth With HIV in the United States.

BACKGROUND: Studies suggest that manualized, measurement-guided, depression treatment is more efficacious than usual care but impact can wane. Our study among youth with HIV (YWH), aged 12-24 years at US clinical research sites in the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, found a significant reduction in depressive symptoms among YWH who received a manualized, measurement-guided treatment. This paper reports outcomes up to 24 weeks after the intervention. METHODS: Eligibility included diagnosis of ongoing nonpsychotic depression. Using restricted randomization, sites were assigned to either combination cognitive behavioral therapy and medication management algorithm tailored for YWH or to enhanced standard of care, which provided psychotherapy and medication management. Site-level mean Quick Inventory for Depression Symptomatology Self-Report (QIDS-SR) scores and proportion of youth with treatment response (>50% decrease from baseline) and remission (QIDS-SR ≤ 5) were compared across arms using t tests. RESULTS: Thirteen sites enrolled 156 YWH, with baseline demographic factors, depression severity, and HIV disease status comparable across arms. At week 36, the site-level mean proportions of youth with a treatment response and remission were greater at combination cognitive behavioral therapy and medication management algorithm sites (52.0% vs. 18.8%, P = 0.02; 37.9% vs. 19.4%, P = 0.05), and the mean QIDS-SR was lower (7.45 vs. 9.75, P = 0.05). At week 48, the site-level mean proportion with a treatment response remained significantly greater (58.7% vs. 33.4%, P = 0.047). CONCLUSIONS: The impact of manualized, measurement-guided cognitive behavioral therapy and medication management algorithm tailored for YWH that was efficacious at week 24 continued to be evident at weeks 36 and 48.

Evaluation of Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV/ΔNS2/Δ1313/I1314L and RSV/276 in RSV-Seronegative Children.

BACKGROUND: This United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion. METHODS: RSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season. RESULTS: Enrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had ≥4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased ≥4-fold in 60% and 92% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses. CONCLUSIONS: Both vaccines had excellent infectivity and were well tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses. CLINICAL TRIALS REGISTRATION: NCT03227029 and NCT03422237.

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.

INTRODUCTION: Adolescents living with HIV are subject to multiple co-morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project. METHODS: Data were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10-17 years, were included. Growth was measured using height-for-age Z-scores (HAZ, stunting if <-2 SD, WHO growth charts). Linear mixed-effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex-specific models with fractional polynomials were used to model non-linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age. RESULTS: A total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two-thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub-Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia-Pacific; 19% overall had CD4 counts <500 cells/mm3 . Across adolescence, higher HAZ was observed in females and among those in high-income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch-up with non-stunted, early ART-treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3 . This decline was observed across all regions, in males and females. CONCLUSIONS: Growth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.

Pharmacokinetics of Tenofovir Alafenamide With Boosted Protease Inhibitors in Pregnant and Postpartum Women Living With HIV: Results From IMPAACT P1026s.

BACKGROUND: Tenofovir alafenamide (TAF) is a key component of HIV treatment, but pharmacokinetic data supporting the use of TAF during pregnancy are limited. In this study, we report pharmacokinetic, safety, and birth outcomes for TAF 25 mg with a boosted protease inhibitor in pregnant women living with HIV. METHODS: IMPAACT P1026s was a multicenter, nonrandomized, open-label, phase IV prospective study. Pregnant women living with HIV receiving TAF 25 mg with a boosted protease inhibitor were eligible. Intensive pharmacokinetic assessments were performed during the second and third trimesters and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery. Infant washout samples were collected through 5-9 days postbirth. Comparisons of paired pharmacokinetic data between pregnancy and postpartum were made using geometric mean ratios (GMR) [90% confidence intervals (CIs)] and Wilcoxon signed-rank tests with P < 0.10 considered significant. RESULTS: Twenty-nine women were enrolled from the United States (median age 31 years and weight 84.5 kg during the third trimester; 48% Black, 45% Hispanic/Latina). TAF AUCtau did not significantly differ in the second [GMR 0.62 (90% CI: 0.29 to 1.34); P = 0.46] or third trimester [GMR 0.94 (90% CI: 0.63 to 1.39); P = 0.50] vs. postpartum and were comparable with historical data in nonpregnant adults. TAF was only quantifiable in 2/25 maternal delivery samples and below the limit of quantification in all cord blood and infant washout samples, likely because of the short half-life of TAF. CONCLUSION: TAF AUCtau did not significantly differ between pregnancy and postpartum. These findings provide reassurance as TAF use during pregnancy continues to expand.

Standardized Definitions of In Utero Human Immunodeficiency Virus and Antiretroviral Drug Exposure Among Children.

In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes.

A Case of in utero Transmission of Drug-resistant HIV in the United States.

Thanks to the development of antiretroviral drugs and the implementation of routine perinatal prophylaxis, primarily containing zidovudine, modern-day rates of perinatal transmission of HIV are very low in developed countries. We present a case of perinatal transmission of HIV with extensive nucleoside reverse transcriptase inhibitor resistance as a reminder that perinatal transmission of resistance mutations can occur. This case calls for further investigation into the utility of using genotype to determine neonatal prophylaxis in the setting of maternal HIV drug resistance.

Pharmacokinetics of Atazanavir Boosted With Cobicistat in Pregnant and Postpartum Women With HIV.

BACKGROUND: This study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples. SETTING: A nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children. METHODS: Intensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Atazanavir and cobicistat were measured in plasma by validated high-performance liquid chromatography-ultraviolet and liquid chromatography-tandem mass spectrometry assays, respectively. A 2-tailed Wilcoxon signed-rank test (α = 0.10) was used for paired within-participant comparisons. RESULTS: A total of 11 pregnant women enrolled in the study. Compared with paired postpartum data, atazanavir AUC0-24 was 26% lower in the second trimester [n = 5, P = 0.1875, geometric mean of ratio (GMR) = 0.739, 90% CI: 0.527 to 1.035] and 54% lower in the third trimester (n = 6, GMR = 0.459, P = 0.1563, 90% CI: 0.190 to 1.109), whereas cobicistat AUC0-24 was 35% lower in the second trimester (n = 5, P = 0.0625, GMR = 0.650, 90% CI: 0.493 to 0.858) and 52% lower in the third trimester (n = 7, P = 0.0156, GMR = 0.480, 90% CI: 0.299 to 0.772). The median (interquartile range) 24-hour atazanavir trough concentration was 0.21 µg/mL (0.16-0.28) in the second trimester, 0.21 µg/mL (0.11-0.56) in the third trimester, and 0.61 µg/mL (0.42-1.03) in postpartum. Placental transfer of atazanavir and cobicistat was limited. CONCLUSIONS: Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission.

Comparison of healthcare resource utilization and costs of patients with HR+/HER2- advanced breast cancer treated with ribociclib versus other CDK4/6 inhibitors.

AIMS: To assess healthcare resource utilization (HRU) and healthcare costs among women with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- aBC) treated with cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors. METHODS: Women with HR+/HER2- aBC, initiating CDK4/6 inhibitor treatment were identified using IBM MarketScan Commercial and Medicare Supplemental databases (Q1/2000-Q3/2018). Based on the first CDK4/6 inhibitor patients received (index therapy), three cohorts were identified: abemaciclib, palbociclib, and ribociclib. The baseline period (six months preceding treatment initiation) was used to describe patient characteristics. All-cause HRU and direct total healthcare costs (medical and pharmacy) from treatment initiation until the earliest of the end of index therapy, continuous health plan enrollment, or data availability, were compared for the ribociclib cohort versus the abemaciclib and palbociclib cohorts, separately, using weighted regression analyses balanced on baseline covariates. RESULTS: Average age at treatment initiation was ∼60 years and the majority of patients were postmenopausal (abemaciclib: 92%; palbociclib: 92%; ribociclib: 79%). Average follow-up duration was 3.9, 8.8, and 5.9 months for the abemaciclib, palbociclib, and ribociclib cohorts, respectively. After reweighting, HRU was not statistically different between the ribociclib and abemaciclib cohorts, however, the ribociclib cohort incurred significantly lower total healthcare costs (-$5,452; 95% CI: -$8,726; -$1,139, p = .01). Medical costs (driven by outpatient costs) and pharmacy costs (driven by CDK4/6 inhibitor costs) were significantly lower for the ribociclib cohort. Among the reweighted ribociclib and palbociclib cohorts, HRU and total healthcare costs were not statistically different, although the ribociclib cohort had lower outpatient costs per-patient-per-month (-$1,245, 95% CI: -$2,349; -$37, p = .04). LIMITATIONS: Due to the retrospective, observational design, treatment cohorts were not randomly assigned. CONCLUSIONS: During CDK4/6 inhibitor therapy, ribociclib patients tended to incur lower medical and pharmacy costs than abemaciclib patients. Among ribociclib and palbociclib patients, HRU and healthcare costs were similar.

Pharmacokinetics of darunavir and cobicistat in pregnant and postpartum women with HIV.

OBJECTIVE: To evaluate darunavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. DESIGN: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of darunavir and cobicistat pharmacokinetics in pregnant women with HIV and their children in the United States. METHODS: Intensive steady-state 24-h pharmacokinetic profiles were performed after administration of 800 mg of darunavir and 150 mg of cobicistat orally in fixed dose combination once-daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Darunavir and cobicistat were measured in plasma by validated HPLC-UV and liquid chromatography with tandem mass spectrometry detection (LC-MS)/MS assays, respectively. A two-tailed Wilcoxon signed-rank test (α = 0.10) was employed for paired within-participant comparisons. RESULTS: A total of 29 pregnant women receiving darunavir and cobicistat once-daily enrolled in the study. Compared with paired postpartum data, darunavir AUC0--24 was 53% lower in the second trimester [n = 12, P = 0.0024, geometric mean of ratio (GMR)=0.47, 90% confidence interval (CI) 0.33 - 0.68] and 56% lower in the third trimester (n = 18, P < 0.0001, GMR = 0.44, 90% CI 0.36 - 0.54), whereas cobicistat AUC0--24 was 50% lower in the second trimester (n = 12, P = 0.0024, GMR = 0.50, 90% CI 0.36-0.69) and 56% lower in the third trimester (n = 18, P < 0.0001, GMR = 0.44, 90% CI 0.35-0.55). Placental transfer of darunavir and cobicistat was limited. CONCLUSION: Standard darunavir/cobicistat dosing during pregnancy results in significantly lower exposure during pregnancy, which may increase the risk of virologic failure and perinatal transmission.

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus.

BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

A Nurse Case Management HIV Prevention Intervention (Come As You Are) for Youth Experiencing Homelessness: Protocol for a Randomized Wait-list Controlled Trial.

BACKGROUND: Youth experiencing homelessness are more likely than housed youth to experience premature death, suicide, drug overdose, pregnancy, substance use, and mental illness. Yet while youth experiencing homelessness are 6 to 12 times more likely to become infected with HIV than housed youth, with HIV prevalence as high as 16%, many do not access the prevention services they need. Despite adversities, youth experiencing homelessness are interested in health promotion programs, can be recruited and retained in interventions and research studies, and demonstrate improved outcomes when programs are tailored and relevant to them. OBJECTIVE: The study aims to compare the efficacy of a nurse case management HIV prevention and care intervention, titled Come As You Are, with that of usual care among youth experiencing homelessness aged 16 to 25 years. METHODS: The study is designed as a 2-armed randomized wait-list controlled trial. Participants (n=450) will be recruited and followed up for 9 months after the intervention for a total study period of 12 months. Come As You Are combines nurse case management with a smartphone-based daily ecological momentary assessment to develop participant-driven HIV prevention behavioral goals that can be monitored in real-time. Youth in the city of Houston, Texas will be recruited from drop-in centers, shelters, street outreach programs, youth-serving organizations, and clinics. RESULTS: Institutional review board approval (Committee for the Protection of Human Subjects, University of Texas Health Science Center at Houston) was obtained in November 2018. The first participant was enrolled in November 2019. Data collection is ongoing. To date, 123 participants have consented to participate in the study, 89 have been enrolled, and 15 have completed their final follow-up. CONCLUSIONS: There is a paucity of HIV prevention research regarding youth experiencing homelessness. Novel and scalable interventions that address the full continuum of behavioral and biomedical HIV prevention are needed. This study will determine whether a personalized and mobile HIV prevention approach can reduce HIV risk among a hard-to-reach, transient population of youth at high risk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26716.

Scale up mHealth HIV interventions: site and public health perspectives and lessons learned from P3.

A number of mobile health (mHealth) interventions have been shown to be effective and highly acceptable tools for improving human immunodeficiency virus (HIV) prevention and care for youth. Scale-up of efficacious technology-based interventions is challenging and best practices for scale-up have not been clearly established. Developers of mHealth interventions should have plans in mind for wide scale implementation throughout all stages of development including planning, during trials and during analysis and dissemination. We discuss an approach of focus on researchers, funders and potential implementers including members of the community, public health practitioners and policymakers during initial planning, trials, analysis and dissemination, and planning for scale-up. Development of the P3 (Prepared, Protected, emPowered) mobile application (app), an intervention built to encourage and increase pre-exposure prophylaxis (PrEP) adherence among young men who have sex with men (YMSM) and young transgender women who have sex with men (YTWSM), is discussed in terms of designing for scale-up and lessons learned.

Using Social Media and Technology to Communicate in Pediatric HIV Research: Qualitative Study With Young Adults Living With or Exposed to Perinatal HIV.

BACKGROUND: As young adults living with perinatal HIV (PHIV) or perinatal HIV exposure but uninfected (PHEU) grow older and manage the challenges and competing demands of young adulthood, new approaches are needed to facilitate their retention in longitudinal research and clinical care beyond in-person clinic visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel virus that causes coronavirus disease (COVID-19), emerged in the United States in January 2020 and has underscored this need; studies are adapting to remote communication with and data collection from participants. However, there are limited data on communication preferences among young adults who are living with PHIV or PHEU. OBJECTIVE: The objectives of this qualitative study were to describe participants' perceptions and use of social media and technology in their personal lives and in the context of participating in longitudinal pediatric HIV research and to describe the implications of the use of technology and social media for communication and retention purposes within a longitudinal pediatric study about HIV. METHODS: We conducted 6 focus group discussions with 31 young adults living with PHIV and 13 in-depth interviews with 6 young adults living with PHIV and 7 living with PHEU. We asked about their preferences for the use of social media and digital technology in the Adolescent Master Protocol, a US-based longitudinal cohort study of youth affected by HIV. RESULTS: Participants' willingness to use social media platforms, telephone calls, SMS text messages, and video calls within the context of HIV research varied due to fears of HIV stigma and inadvertent disclosure. However, trusting relationships with clinical staff positively impacted their willingness to use these platforms. CONCLUSIONS: Our findings offer insight into how pediatric studies and clinics can communicate with participants as they age, even as new technologies and social media platforms emerge and replace old ones. For optimal retention, pediatric clinical staff should consider communication approaches offering flexible and tailored options for young adults participating in HIV research.

Trends in post-partum viral load among women living with perinatal HIV infection in the USA: a prospective cohort study.

BACKGROUND: Small studies reported poor post-partum outcomes among young women living with perinatal HIV infection who are now ageing into adulthood and becoming pregnant. For targeted clinical intervention, we sought to identify women in this population at risk of poor post-partum virological control. METHODS: We abstracted data on pregnancy history for women living with perinatal HIV infection in the Pediatric HIV/AIDS Cohort Study-AMP Up protocol, a prospective study of young adults living with perinatal HIV from 14 sites in the USA. Linear models with generalised estimating equations described trends in HIV viral load through 1 year post-pregnancy by pregnancy outcome. We used group-based trajectory modelling to identify viral load trajectory groups in the first post-partum year after livebirths. We then compared sociodemographic and clinical factors across identified groups. We defined viraemia as 400 copies per mL or more. FINDINGS: Between April 15, 2014, and Oct 1, 2017, we enrolled 323 women, of whom 234 had perinatal HIV infection, and reported age at sexual debut and history of heterosexual vaginal intercourse. Of the 172 pregnancies recorded in these women, 147 (85%, 104 livebirths and 43 spontaneous or elective abortions) were eligible for post-pregnancy viral load trajectory analyses (ie, had at least two viral loads in the year after end of pregnancy). Viral load increased by 0·7 log10 copies per mL (95% CI 0·5 to 1·0) in the first 12 weeks post partum after 104 livebirths, and subsequently stabilised from 13 weeks to 1 year post partum (slope -0·01 log10 copies per mL, 95% CI -0·3 to 0·3). By comparison, the average viral load trajectory after 43 spontaneous or elective abortions remained at less than 400 copies per mL. We identified three distinct groups of viral load trajectories after 104 livebirths, classified as reflecting sustained suppression (31 [30%]), rebound viraemia (55 [53%]), and persistent viraemia (18 [17%]). Women with sustained post-partum suppression were older at conception (22·9 years, IQR 19·4-25·9) than those with rebound viraemia (20·4 years, 18·8-22·2), or persistent post-partum viraemia (19·0 years, 17·7-20·5). Pre-conception viraemia and immune suppression were also strong risk factors for post-partum viraemia. INTERPRETATION: Despite success achieving viral load suppression during pregnancy, women living with perinatal HIV infection have a high risk of post-partum viraemia. Younger age at conception, pre-conception viraemia, and pre-conception immune suppression could identify women in this population most likely to benefit from post-partum adherence interventions. FUNDING: National Institutes of Health.

Testing the Testers: Are Young Men Who Have Sex With Men Receiving Adequate HIV Testing and Counseling Services?

BACKGROUND: The United States Centers for Disease Control and Prevention promote HIV testing every 6 months among young men who have sex with men (YMSM) to facilitate entry into the HIV prevention and care continuum. Willingness to be tested may be influenced by testing services' quality. Using a novel mystery shopper methodology, we assessed YMSM's testing experiences in 3 cities and recommend service delivery improvements. METHODS: We assessed YMSM's experiences at HIV testing sites in Philadelphia (n = 30), Atlanta (n = 17), and Houston (n = 19). YMSM (18-24) were trained as mystery shoppers and each site was visited twice. After each visit, shoppers completed a quality assurance survey to evaluate their experience. Data were pooled across sites, normed as percentages, and compared across cities. RESULTS: Across cites, visits averaged 30 minutes (SD = 25.5) and were perceived as welcoming and friendly (70.9%). YMSM perceived most sites respected their privacy and confidentiality (84.3%). YMSM noted deficiencies in providers' competencies with sexual minorities (63.4%) and comfort during the visit (65.7%). Sites underperformed on Lesbian, Gay, Bisexual, Transgender visibility (49.6%) and medical forms inclusivity (57.95%). Sites on average did not discuss YMSM's relationship context (49.8%) nor provide risk reduction counseling (56.8%) or safer sex education (24.3%). Sites delivered pre-exposure prophylaxis information and counseling inconsistently (58.8%). CONCLUSIONS: Testing sites' variable performance underscores the importance of improving HIV testing services for YMSM. Strategies are recommended for testing sites to promote cultural sensitivity: funding staff trainings, creating systems to assess adherence to testing guidelines and best practices, and implementing new service delivery models.

Nonadherence and unsuppressed viral load across adolescence among US youth with perinatally acquired HIV.

OBJECTIVE: To identify factors associated with nonadherence and unsuppressed viral load across adolescence among youth with perinatally acquired HIV. DESIGN: Longitudinal study at 15 US clinical sites. METHODS: Self-reported antiretroviral medication nonadherence (any missed dose, past week) and unsuppressed viral load (HIV RNA > 400 copies/ml) were assessed annually. Individual, caregiver, social, and structural factors associated with nonadherence and unsuppressed viral load were identified by age (years): 8-11 (preadolescence), 12-14 (early adolescence), 15-17 (middle adolescence), and 18-22 (late adolescence/young adulthood), utilizing multivariable generalized linear mixed effects models. RESULTS: During a median 3.3-year follow-up, 381 youth with perinatally acquired HIV contributed viral load measurements and 379 completed 1190 adherence evaluations. From preadolescence to late adolescence/young adulthood, prevalence of nonadherence increased from 31 to 50% (P < 0.001); prevalence of unsuppressed viral load increased from 16 to 40% (P < 0.001). In adjusted analyses, in pre, middle, and late adolescence/young adulthood, perceived antiretroviral side effects were associated with nonadherence. Additional factors associated with nonadherence included: in preadolescence, using a buddy system (as an adherence reminder); in early adolescence, identifying as black, using buddy system; in middle adolescence, CD4% less than 15%, unmarried caregiver, indirect exposure to violence, stigma/fear of inadvertent disclosure, stressful life events. Associations with unsuppressed viral load included: in early adolescence, youth unawareness of HIV status, lower income; in middle adolescence, perceived antiretroviral side effects, lower income; in late adolescence/young adulthood, distressing physical symptoms, and perceived antiretroviral side effects. CONCLUSION: Prevalence of nonadherence and unsuppressed viral load increased with age. Associated factors varied across adolescence. Recognition of age-specific factors is important when considering strategies to support adherence.

Sertraline Pharmacokinetics in HIV-Infected and Uninfected Children, Adolescents, and Young Adults.

Objective: Due to potential disease and drug interactions, the appropriate sertraline starting dose and titration range may require adjustment in pediatric patients living with HIV. This is the first report of sertraline pharmacokinetics in HIV-infected youth. Methods: IMPAACT P1080 was a multicenter pilot study describing psychiatric medication pharmacokinetics in HIV-infected and uninfected youth. Participants were stable on sertraline, >6 to <25 years old, and (1) HIV-uninfected (HIV(-)), (2) HIV-infected taking efavirenz (EFV), or (3) HIV-infected taking boosting ritonavir/protease inhibitor (PI/r). Sampling occurred at pre-dose, 2, 4, 6, 12, and 24-h post-dose. Analyses were performed for sertraline and N-desmethylsertraline, and CYP2D6 phenotyping was completed with dextromethorphan. Results: Thirty-one participants (16 HIV(-), 12 PI/r, and 3 EFV) had median (range) weight, age, and dose of 69.5 (31.5-118.2) kg, 21.8 (9.1-24.7) years, and 75.0 (12.5-150.0) mg once daily. Sertraline exposure was highest for HIV(-) and lowest for EFV cohorts; median dose-normalized AUC 0-24 was 1176 (HIV(-)), 791 (PI/r) and 473 (EFV) ng*hr/mL, and C24 was 32.7 (HIV(-)), 20.1 (PI/r), and 12.8 (EFV) ng/mL. The urinary dextromethorphan/dextrorphan (DXM/DXO) ratio was higher in HIV(-) vs. PI/r cohorts (p = 0.01). Four HIV(-) participants were CYP2D6 poor metabolizers (ln(DXM/DXO) of >-0.5). Conclusions: HIV(-) cohort had the highest sertraline exposure. Sertraline exposure was ~40% lower in the PI/r cohort than in HIV(-); the need to alter sertraline dose ranges for PI/r participants is not clear. The impact of efavirenz on sertraline needs further investigation due to limited numbers of EFV participants.

NK cells in treated HIV-infected children display altered phenotype and function.

BACKGROUND: Chronic HIV infection is known to trigger a population redistribution and alteration in the functional capacity of natural killer (NK) cells. Because of improved antiretroviral treatments, there are rising numbers of adolescents and young adults worldwide who are living with HIV infection since birth. OBJECTIVE: We sought to determine how NK-cell phenotypic and functional subsets are altered in treated pediatric patients. METHODS: NK cells were contrasted among 29 HIV-unexposed and uninfected controls (5-19 years), 23 HIV-exposed but uninfected patients (3-19 years), and 25 HIV-infected patients (3-19 years) using multiparametric flow cytometry. RESULTS: Although most NK-cell markers did not differ, activating receptors such as NKp46, DNAX accessory molecule-1, and NKG2C and stimulatory receptors such as CD2 and CD11c were expressed by a higher frequency of NK cells in HIV-infected patients than in controls. Interestingly, there were less differences between HIV-infected and HIV-exposed but uninfected children. There was an inverse relationship between CD4/CD8 T-cell ratio (as a marker of disease progression) and CD11c and NKG2C frequency and CD69 upregulation on stimulation among HIV-infected patients. CONCLUSIONS: A chronic NK-cell activation phenotype persists in HIV-infected children receiving antiretroviral therapy and is associated with declining CD4/CD8 T-cell ratios. A lower CD4/CD8 T-cell ratio was associated with higher baseline granzyme B (P = .0068; R2 = 0.29) and degranulation potential (P = .022; R2 = 0.22) in stimulated NK cells. Thus, NK cells in HIV-infected children receiving treatment have reduced functional potential and an activated phenotype that distinguishes them from uninfected children.