Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens.

OBJECTIVE: To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. DESIGN: Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. METHODS: We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. RESULTS: We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. CONCLUSION: Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.

An International Prospective Cohort Study of HIV and Zika in Infants and Pregnancy (HIV ZIP): Study Protocol.

Zika virus (ZIKV) infection may adversely affect pregnancies of women living with HIV (WLHIV). Because no study to date has focused on maternal and child effects of HIV and ZIKV co-infection in pregnant women, we undertook the International Prospective Cohort Study of HIV and Zika in Infants and Pregnancy (HIV ZIP). The aims of this two-phase study of pregnant women and their infants are to compare the incidence of ZIKV infection among pregnant women with and without HIV infection and to determine the risk of adverse maternal and child outcomes associated with ZIKV/HIV co-infection at clinical sites in Brazil, Puerto Rico, and the continental United States. Phase I was designed to enroll pregnant women/infant pairs who were: (1) infected with HIV only, (2) infected with ZIKV only, (3) infected with HIV and ZIKV, and (4) not infected with either HIV or ZIKV. A key goal of this phase was to assess the feasibility of enrolling 200 women/infant pairs within a year, with a target of 150 WLHIV, 50 HIV-uninfected women, and a minimum of 20 who were co-infected with HIV and ZIKV. If the feasibility of Phase I proved successful, Phase II would enroll up to 1,800 additional pregnant women/infant pairs to the same four groups. Enrolled women in both phases were to be followed throughout their pregnancy and up to 6 weeks post-partum. Infants were also to be followed for 1 year after birth. To date, Phase 1 data collection and follow-up have been completed. Delineation of possible harmful effects of HIV/ZIKV co-infection will allow the formulation of standard-of-care recommendations to minimize adverse effects but enable the continuation of preventive HIV therapy. Furthermore, while the prospective HIV ZIP study was developed before the COVID pandemic, it is especially relevant today since it can be easily adapted to provide critically important information on the impact of COVID-19 infection or other still unrecognized new agents among pregnant women and their offspring worldwide.

The HIV Continuum of Care for Adolescents and Young Adults Attending 13 Urban US HIV Care Centers of the NICHD-ATN-CDC-HRSA SMILE Collaborative.

BACKGROUND: Almost one-quarter of all new HIV diagnoses in the United States occur among persons aged 13-24 years. These youths have the poorest HIV care continuum (HCC) outcomes, yet few empirical youth-specific data are available. METHODS: The Strategic Multisite Initiative for the Identification, Linkage, and Engagement in Care of HIV-infected youth (SMILE) helped HIV-infected (mostly newly diagnosed) youth, aged 12-24 years, link to youth-friendly care, and evaluated each milestone of the HCC (October 2012-September 2014). Numbers of HIV-infected youth referred, linked, engaged, and retained in care were recorded, along with sociodemographics. Viral suppression (VS) was defined as ≥1 HIV viral load (VL) below the level of detection on study. Correlates of VS were examined using Cox proportional hazards models. RESULTS: Among 1411 HIV-infected youth, 1053 (75%) were linked, 839 (59%) engaged, and 473 (34%) retained in care at adolescent health care sites. Antiretroviral therapy was initiated among 474 (34%), and 166 (12%) achieved VS. Predictors of VS included lower VL at baseline [aHR 1.56 (95% CI: 1.32-1.89), P < 0.0001], recent antiretroviral therapy receipt [aHR 3.10 (95% CI: 1.86-5.18), P < 0.0001], and shorter time from HIV testing until referral to linkage coordinator [aHR 2.52 (95% CI: 1.50-4.23), P = 0.0005 for 7 days to 6 weeks and aHR 2.08 (95% CI: 1.08-4.04), P = 0.0294 for 6 weeks to 3 months compared with >3 months]. CONCLUSIONS: Although this large national sample of predominately newly diagnosed youths linked to care at similar rates as adults, they achieved disproportionately lower rates of VS. Prompt referral to youth-friendly linkage services was an independent predictor of VS. Youth-focused interventions are urgently needed to improve their HCC outcomes.

HIV Continuum of Care for Youth in the United States.

BACKGROUND: Beneficial HIV treatment outcomes require success at multiple steps along the HIV Continuum of Care. Youth living with HIV are a key population, and sites in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) are known for modeling optimum HIV adolescent care. METHODS: A longitudinal cohort study conducted at 14 network sites across the United States assessed how the later steps of the Continuum of Care were achieved among the youth: engagement, treatment, and viral load (VL) suppression. Youth aged 13-24 who were behaviorally infected with HIV and linked to care at an ATN-affiliated site were eligible to participate. RESULTS: A total of 467 youth were enrolled and had 1 year of available data. Most were aged 22-24 (57%), male (79%), and black/non-Hispanic (71%). Most used alcohol (81%) and marijuana (61%) in the 3 months before enrollment, and 40% had a history of incarceration. Among this cohort of youth, 86% met criteria for care engagement; among these, 98% were prescribed antiretroviral therapy and 89% achieved VL suppression. Sustained VL suppression at all measured time points was found among 59% with initial suppression. Site characteristics were notable for the prevalence of adherence counseling (100%), case management (100%), clinic-based mental health (93%), and substance use (64%) treatment. CONCLUSIONS: Youth living with HIV in the United States can be successfully treated at health care sites with experience, excellence, and important resources and services. Sustained VL suppression may be an important step to add to the Continuum of Care for youth.

Exchange of Sex for Drugs or Money in Adolescents and Young Adults: An Examination of Sociodemographic Factors, HIV-Related Risk, and Community Context.

The goal of this research was to examine associations among sociodemographic factors, HIV risk, and community context (e.g., economic insecurity, job training, housing instability, crime victimization, and perceived community norms) in adolescents and young adults who ever exchanged sex for drugs or money. Anonymous survey data were collected using ACASIs at community venues where adolescents and young adults congregate in resource-challenged, STI prevalent, urban, US neighborhoods. Conventional descriptive statistics, Fisher's exact tests, and generalized estimating equations approaches were used to examine associations. Participants (1818, 95.5 % of those screened eligible) were, on average, aged 21.0 years; 42.2 % were males, and 4.6 % were transgender. Almost one-third (32.1 %) identified as gay or lesbian, 18.1 % identified as bisexual; 66.2 % were Black and 21.0 % were Hispanic; 1.3 % was 'living on the street'. A sizeable proportion reported HIV-related risk: 16.3 % exchanged sex, 12.6 % had sex with someone they knew to be HIV-infected, 7.8 % had sex with someone who injected drugs, and 1.3 % injected drugs. Multivariate comparisons identified a number of variables (e.g., being male or transgender, homelessness, sex with a partner who has HIV, STI history, unemployment, job training access, housing instability, crime victimization, perceived community norms) that were significantly associated with exchange of sex (p < 0.05). This research contributes to the knowledge-base regarding exchange of sex among adolescents and young adults, particularly as it relates to community context. Longitudinal studies to describe the trajectory of social, health, and physical risks and consequences are needed for development of effective evidence-based prevention strategies.

Evaluation of the effect of human immunodeficiency virus-related structural interventions: the connect to protect project.

IMPORTANCE: With the emphasis on structural-level interventions that target social determinants of human immunodeficiency virus (HIV) transmission to curb the HIV epidemic, there is a need to develop evaluation models that can detect changes in individual factors associated with HIV-related structural changes. OBJECTIVE: To describe whether structural changes developed and achieved by community coalitions are associated with an effect on individual factors associated with the risk of contracting HIV. DESIGN, SETTING, AND PARTICIPANTS: In this serial cross-sectional survey design, data were collected from 8 cities during 4 rounds of annual surveys from March 13, 2007, through July 29, 2010. Study recruitment took place at venues where the population of focus was known to congregate, such as clubs, bars, community centers, and low-income housing. The convenience sample of at-risk youth (persons aged 12-24 years) included 5337 individuals approached about the survey and 3142 (58.9%) who were screened for eligibility. Of the 2607 eligible participants, 2559 (98.2%) ultimately agreed to participate. INTERVENTIONS: Achievement of locally identified structural changes that targeted public and private entities (eg, federal agencies, homeless shelters, and school systems) with the goal of fostering changes in policy and practice to ultimately facilitate positive behavioral changes aimed at preventing HIV. MAIN OUTCOMES AND MEASURES: Number of sexual partners, partner characteristics, condom use, and history of sexually transmitted infections and HIV testing. RESULTS: Exposure to structural changes was not statistically significantly associated with any of the outcome measures, although some results were in the direction of a positive structural change effect (eg, a 10-unit increase in a structural change score had an odds ratio of 0.88 [95% CI, 0.76-1.03; P = .11] for having an older sexual partner and an odds ratio of 0.91 [95% CI, 0.60-1.39; P = .39] for using a condom half the time or less with a casual partner). CONCLUSIONS AND RELEVANCE: This study evaluated a broad representation of at-risk individuals and assessed the effect of numerous structural changes related to various HIV risk factors. No structural changes as measured in this study were associated with a statistically significant reduction in risk behaviors. These null findings underscore the need for a long-term approach in evaluating structural interventions and the development of more nuanced methods of quantifying and comparing structural-change initiatives and determining the appropriate strategies for evaluating effect.

HIV viral load levels and CD4+ cell counts of youth in 14 cities.

OBJECTIVES: To describe the HIV viral load and CD4 cell counts of youth (12-24 years) in 14 cities from March 2010 through November 2011. METHODS: Baseline HIV viral load and CD4 cell count data were electronically abstracted in a central location and in an anonymous manner through a random computer-generated coding system without any ability to link codes to individual cases. RESULTS: Among 1409 HIV reported cases, 852 participants had data on both viral load and CD4 cell counts. Of these youth, 34% had CD4 cell counts of 350 or less, 27% had cell counts from 351 to 500, and 39% had CD4 cell counts greater than 500. Youth whose transmission risk was male-to-male sexual contact had higher viral loads compared with youth whose transmission risk was perinatal or heterosexual contact. Greater than 30% of those who reported male-to-male sexual contact had viral loads greater than 50 000 copies, whereas less than 20% of heterosexual contact youth had viral loads greater than 50 000 copies. There were no differences noted in viral load by type of testing site. CONCLUSION: Most HIV-infected youth have CD4 cell counts and viral load levels associated with high rates of sexual transmission. Untreated, these youth may directly contribute to high rates of ongoing transmission. It is essential that any public health test and treat strategy place a strong emphasis on youth, particularly young MSM.

Linkage to care for HIV-positive adolescents: a multisite study of the adolescent medicine trials units of the adolescent trials network.

PURPOSE: To understand linkage to care practices at sites providing clinical services to newly diagnosed HIV-positive adolescents. METHODS: Qualitative analysis of detailed interviews conducted with 28 personnel involved in linkage to care at 15 sites providing specialty care to HIV-positive adolescents. RESULTS: We showed that multiple models exist for linkage to care, and that both formal and informal community relationships are important for successful linkage to care. Stigma was seen as a universal issue, enhancing the importance of the balance of confidentiality and social support. Barriers to care, such as mental health issues, substance use, and transportation, are common. CONCLUSIONS: We conclude that the complexity of linkage to care requires thought and planning as HIV testing is expanded to lower-risk populations.

Low bone mass in behaviorally HIV-infected young men on antiretroviral therapy: Adolescent Trials Network Study 021B.

BACKGROUND: Peak bone mass is achieved in adolescence/early adulthood and is the key determinant of bone mass in adulthood. We evaluated the association of bone mass with human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) during this critical period among behaviorally HIV-infected young men and seronegative controls. METHODS: HIV-positive men (N = 199) and HIV-negative controls (N = 53), ages 14-25 years, were studied at 15 Adolescent Trials Network for HIV/AIDS Interventions sites. HIV-positive participants were recruited on the basis of ART status: ART-naive (N = 105) or on a regimen containing a nonnucleoside reverse transcriptase inhibitor (NNRTI; N = 52) or protease inhibitor (PI; N = 42). Bone mineral density (BMD) and content (BMC) and body composition were measured by dual-energy X-ray absorptiometry (DXA). Results were compared across groups by linear modeling. Bone results were adjusted for race, body mass index (BMI), and type of DXA (Hologic/Lunar). RESULTS: The HIV-positive and HIV-negative groups had comparable median age (21 years) and racial/ethnic distribution. Median times since HIV diagnosis were 1.3, 1.9, and 2.2 years in the ART-naive, NNRTI, and PI groups, respectively (P = .01). Total and regional fat were significantly lower in the ART-naive group compared with seronegative controls. Mean BMD and Z scores were generally lower among HIV-positive participants on ART, particularly in the PI group. Average Z scores for the spine were below zero in all 4 groups, including controls. CONCLUSIONS: Young men on ART with a relatively recent diagnosis of HIV infection have lower bone mass than controls. Longitudinal studies are required to determine the impact of impaired accrual or actual loss of bone during adolescence on subsequent fracture risk.

Hepatitis B vaccination in HIV-infected youth: a randomized trial of three regimens.

BACKGROUND: HIV-infected youth are at risk of hepatitis B infection and should be vaccinated. Previous reports suggest reduced response to standard hepatitis B vaccine regimens. METHODS: HIV-infected youth, aged 12 to younger than 25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B, 20 µg HBsAg; Arm 2: Engerix B (GlaxoSmithKline, Rixensart, Belgium), 40 µg; and Arm 3: Twinrix (GlaxoSmithKline, Rixensart, Belgium), 20 µg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at Weeks 0, 4, and 24. RESULTS: Characteristics of evaluable patients (n = 336) at entry were similar in the study arms. At enrollment, median CD4+ T-cell count was 460 cells/mm3 (interquartile range, 305-668); 13% were less than 200 cells/mm3. Among Engerix B, 20-µg recipients, 60.4% responded to vaccine (HBsAb 10 IU/mL or greater at Week 28). Improved vaccine response was seen in recipients of Engerix B, 40 µg (73.2% versus Arm 1, P = 0.04) and Twinrix (75.4% versus Arm 1, P = 0.02). In multivariate analysis, only baseline CD4+ T-cell count and study arm were independent predictors of vaccine response. CONCLUSIONS: In HIV-infected youth, a three-dose vaccination regimen with Engerix B, 40 µg, or Twinrix and higher baseline CD4+ T-cell counts were independently associated with improved vaccine response.

Obesity and dyslipidemia in behaviorally HIV-infected young women: Adolescent Trials Network study 021.

BACKGROUND: The goal of this study was to determine the nature and prevalence of abnormalities in lipids, glucose metabolism, and body composition in behaviorally human immunodeficiency virus (HIV)-infected young women and the relationship of these abnormalities to different classes of antiretroviral therapy regimens. METHODS: We conducted a cross-sectional, multicenter study involving 173 behaviorally HIV-infected women aged 14-24 years and 61 HIV-seronegative control subjects. HIV-infected women were categorized as follows: antiretroviral therapy naive (n=85), receiving a regimen containing a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n=33), receiving a regimen containing a protease inhibitor (PI; n=36), or receiving a regimen not containing an NNRTI or a PI (n=19). Measurements included fasting lipid levels, glucose and insulin levels before and 2 hours after an oral glucose challenge, high-sensitivity C-reactive protein (hsCRP) levels, anthropometry, fat distribution (measured by dual energy X-ray absorptiometry), and antiretroviral therapy and medical histories. Race-adjusted results were compared across groups and within HIV-infected groups. RESULTS: The median age of participants was 20 years. Of HIV-infected subjects, 77% were African American, 35% smoked cigarettes, and 32% reported exercising regularly. More than 40% had a body mass index > or =25. Triglycerides; total, high-density lipoprotein (HDL), and non-HDL cholesterol; and hsCRP levels differed significantly among groups, with higher levels being most common among those receiving antiretroviral therapy. Indices of glucose metabolism did not differ among groups. In general, cholesterol levels, hsCRP levels, and indices of glucose metabolism worsened as body mass index increased. CONCLUSIONS: Obesity, dyslipidemia, and inflammation were prominent among HIV-infected adolescent women and, coupled with other risk factors, may accelerate the lifetime risk of cardiovascular disease and other adverse events. These results underscore the need for a multifaceted approach to addressing risk reduction in this population.

Recruitment and retention of adolescent participants in HIV research: findings from the REACH (Reaching for Excellence in Adolescent Care and Health) Project.

PURPOSE: To evaluate the importance of 13 items in the recruitment and retention of HIV-positive and HIV-negative adolescent participants in a longitudinal study (REACH study). METHODS: A confidential, self-administered, visual analog, cross-sectional survey was offered to active participants (November 1999-August 2000) with 438 subjects (86%) participating. Sixty-six percent of the cohort were HIV-positive and 34% were HIV-negative with a mean age of 17 years, and 76% were female. Subjects were asked to recall the importance they placed on 13 items in deciding to join the REACH study (recruitment) and to remain on study (retention). Factors that might explain the judgment placed on the items were analyzed using the nonparametric Wilcoxon Rank-Sum test or the Kruskall-Wallis test. RESULTS: The five most important factors for study recruitment were identical to those chosen for retention by participants. The factors were: (a) quality medical care, (b) caring staff, (c) health education, (d) privacy/confidentiality, and (e) altruism. Items judged least important were social activities, compensation, transportation, and food/meals. Subject characteristics (gender, age, HIV status) were not associated with statistically different mean judgment scores at recruitment and retention, although clinical site showed significant variation. Factors that could render subjects vulnerable (health insurance, family finances) were not associated with related items. CONCLUSIONS: Adolescents found quality health care and care team characteristics critically important in considering research participation. Attention to privacy and the opportunity to be altruistic were also important. Compensation for participation was not a significant factor for recruitment and retention of this adolescent cohort. This study demonstrates that adolescents apply sound criteria in evaluating research participation and do not appear to be unduly affected by compensation.