Marvin Belzer

Antiretroviral medication adherence among the REACH HIV-infected adolescent cohort in the USA

Adherence to highly active antiretroviral therapy (HAART) was investigated among HIV-infected adolescents recruited from 13 US cities into the REACH (Reaching for Excellence in Adolescent Care and Health) project, the first large-scale disease progression study of HIV-positive adolescents infected through sexual behaviour or injection drug use. Of 161 subjects, 7% could not correctly identify all their prescribed medications; 11% could identify them but reported never taking at least one medication. The majority (83%) reported taking all of their medications at least some of the time, but only 50% of these subjects reported full adherence. Therefore, only 41% of the sample reported full adherence. A strong association was found between adherence and reduced viral load. A CD4 level of ≥ 500 cells/mm 3 was also associated with adherence. Higher levels of depression were significantly associated with decreased adherence, and a trend was found for an association between number of medications prescribed and adherence. Strict adherence to HAART is critical for sustained suppression of viral replication allowing for immune recovery and reducing the risk of the selection of antiviral resistance. Adherence appears to be a serious problem among HIV-positive adolescents. Better education, intervention to relieve depression, and efforts to improve ease of medication use are essential.

Syndemic theory and HIV-related risk among young transgender women: the role of multiple, co-occurring health problems and social marginalization.

OBJECTIVES We assessed whether multiple psychosocial factors are additive in their relationship to sexual risk behavior and self-reported HIV status (i.e., can be characterized as a syndemic) among young transgender women and the relationship of indicators of social marginalization to psychosocial factors. METHODS Participants (n = 151) were aged 15 to 24 years and lived in Chicago or Los Angeles. We collected data on psychosocial factors (low self-esteem, polysubstance use, victimization related to transgender identity, and intimate partner violence) and social marginalization indicators (history of commercial sex work, homelessness, and incarceration) through an interviewer-administered survey. RESULTS Syndemic factors were positively and additively related to sexual risk behavior and self-reported HIV infection. In addition, our syndemic index was significantly related to 2 indicators of social marginalization: a history of sex work and previous incarceration. CONCLUSIONS These findings provide evidence for a syndemic of co-occurring psychosocial and health problems in young transgender women, taking place in a context of social marginalization.

Transgender Female Youth and Sex Work: HIV Risk and a Comparison of Life Factors Related to Engagement in Sex Work

This study examined the HIV risk behaviors and life experiences of 151 transgender female youth, ages 15–24, in Los Angeles and Chicago. Descriptive analyses and logistic regression modeling were used to identify life factors associated with ever having engaged in sex work. Sixty-seven percent of participants had ever engaged in sex work and 19% self-reported being HIV positive. Many factors were significantly associated with sex work for this sample population. A final multivariate logistic regression model found that lower education status, homelessness, use of street drugs, and perceived social support remained significantly associated with sex work when controlling for other factors. Findings highlight the complex HIV risk environment and suggest a need for sex work initiation research for transgender female youth. HIV prevention efforts for this population need to include broad-based approaches that take into account individual, social, and community-level factors relevant to the lives of transgender female youth.

Parental Support and Mental Health Among Transgender Adolescents

PURPOSE Family support is protective against health risks in sexual minority individuals. However, few studies have focused specifically on transgender youth, who often experience rejection, marginalization, and victimization that place them at risk for poor mental health. This study investigated the relationships among parental support, quality of life, and depression in transgender adolescents. METHODS A total of 66 transgender youth presenting for care at Childrens Hospital Los Angeles completed a survey assessing parental support (defined as help, advice, and confidante support), quality of life, and depression. Regression analyses assessed the associations between parental support and mental health outcomes. RESULTS Parental support was significantly associated with higher life satisfaction, lower perceived burden of being transgender, and fewer depressive symptoms. CONCLUSIONS Parental support is associated with higher quality of life and is protective against depression in transgender adolescents. Interventions that promote parental support may significantly affect the mental health of transgender youth.

Antiretroviral adherence issues among HIV-positive adolescents and young adults.

A total of 31 youth from a multidisciplinary adolescent human immunodeficiency virus clinic were surveyed to gain information about their adherence to complex antiretroviral regimens and elucidate factors that may be associated with adherence. Results indicated that 61% of subjects reported >90% compliance with their medications in the previous 90 days.

Virologic and Immunologic Outcomes after 24 Weeks in HIV Type 1-Infected Adolescents Receiving Highly Active Antiretroviral Therapy

BACKGROUND Adolescents represent the fastest growing demographic group of new human immunodeficiency virus (HIV) infections in the United States. At present, there is little information available about their response to therapy. METHODS We studied 120 adolescents infected via high-risk behaviors who began receiving highly active antiretroviral therapy (HAART), to determine their virologic and immunologic response to therapy. RESULTS Subjects were enrolled at 28 sites of the Pediatric Acquired Immunodeficiency Syndrome Clinical Trials Group. After 16-24 weeks of HAART, 59% of subjects had reproducible undetectable virus loads, according to repeat measurements (virologic success). As enumerated by flow-cytometric analysis, increases in levels of CD4 helper cells (both naive and memory) and decreases in levels of CD8 suppressor cells were observed. Partial restoration of some immunologic parameters for patients who did not achieve virologic success was also observed, but to a more limited extent than for adolescents with virologic success. Adherence to HAART was the only predictor of achieving undetectable virus loads. CONCLUSIONS Adolescents have the capacity to improve their immunologic status with HAART. Lower than expected success in virologic control is related to lack of adherence, and efforts to improve treatment outcome must stress measures to assure adherence to medication.

The relationship of unsafe sexual behavior and the characteristics of sexual partners of HIV infected and HIV uninfected adolescent females

PURPOSE To compare characteristics of sexual relationships in HIV infected and HIV uninfected female adolescents and their association with condom use. METHODS HIV infected and uninfected subjects, aged 13-19 years, were enrolled in a prospective HIV study from 15 sites in 13 U.S. cities. Baseline data on demographic information, substance use, sexual behavior, partner information, and condom use were collected through direct and computer-assisted interviews from currently sexually active females. Univariate, multiple logistic regression, and repeated measures analyses were employed. RESULTS Data from 153 HIV infected and 90 HIV uninfected female subjects showed, on average, that current partners were 4-6 years older. In multivariate analysis, HIV infected subjects were older (OR = 1.37; 95% CI: 1.04-1.81), had more lifetime partners (OR = 2.23; 95% CI: 1.03-4.82), initiated consensual vaginal sex earlier (OR = .74; 95% CI:.58-.95), perceived partner to also be HIV infected (OR = 7.46; 95% CI: 3.2-17.4), and had less unprotected sex (OR = .27; 95% CI:.16-.45). Length of relationship was associated with more unprotected sex for both HIV infected and uninfected subjects (OR = 2.59, 95% CI: 1.27-5.27, OR = 4.13; 95% CI: 1.31-13.05, respectively). Mean partner age difference was greater among HIV infected than for HIV uninfected (OR = 1.06; 95%CI: 1.01-1.12); this greater age difference for HIV infected females was associated with less protection (OR = 1.09; 95% CI: 1.03-1.15). HIV disclosure influenced condom use: without disclosure, less condom use was reported (OR = 6.8; 95% CI: 2.29-20.24) controlling for perception that partner was also HIV infected (OR = 1.1; 95% CI: 1.02-1.21). CONCLUSIONS Because age differential influenced reported condom use, more research, particularly qualitative, is needed into the dynamics of these relationships. Prevention efforts must address partners, particularly older ones.

Identification of Ongoing Human Immunodeficiency Virus Type 1 (HIV-1) Replication in Residual Viremia during Recombinant HIV-1 Poxvirus Immunizations in Patients with Clinically Undetectable Viral Loads on Durable Suppressive Highly Active Antiretroviral Therapy

ABSTRACT In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who achieve viral loads of <50 copies/ml during highly active antiretroviral therapy (HAART), low levels of plasma virus remain detectable for years by ultrasensitive methods. The relative contributions of ongoing virus replication and virus production from HIV-1 reservoirs to persistent low-level viremia during HAART remain controversial. HIV-1 vaccination of HAART-treated individuals provides a model for examining low-level viremia, as immunizations may facilitate virus replication and sequence evolution. In a phase 1 trial of modified vaccinia virus Ankara/fowlpox virus-based HIV-1 vaccines in 20 HIV-infected young adults receiving HAART, we assessed the prevalence of low-level viremia and sequence evolution, using ultrasensitive viral load (<6.5 copies/ml) and genotyping (five-copy sensitivity) assays. Viral evolution, consisting of new drug resistance mutations and novel amino acid changes within a relevant HLA-restricted allele (e.g., methionine, isoleucine, glutamine, or arginine for leucine at position 205 of RT), was found in 1 and 3 of 20 subjects, respectively. Sequence evolution was significantly correlated with levels of viremia of between 6.5 and <50 copies/ml (P = 0.03) and was more likely to occur within epitopes presented by relevant HLA alleles (P < 0.001). These findings suggest that ongoing virus replication contributes to low-level viremia in patients on HAART and that this ongoing replication is subject to CD8+ T-cell selective pressures.

Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort

PURPOSE To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and high-risk HIV uninfected youth and examine associations with responsiveness in the HIV infected group. METHODS Cohorts within the Reaching for Excellence in Adolescent Care and Health (REACH) study population were defined based on receipt of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb. For HBsAb, a value of > 10 International Units per liter was considered a positive response, and the data were collected as either positive or negative from each of the reporting laboratories. Covariates of responsiveness were explored in univariate and multivariate models for each cohort. RESULTS Sixty-one subjects had received a three-dose vaccination course at the time of entry into REACH. HIV uninfected subjects had significantly higher rates of response by serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR = .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received three vaccinations with at least one occurring in the study period. The rates of response were similar for the HIV infected and uninfected groups (37.1% vs. 37.5%) in this cohort. Univariate and multivariate analysis in the prospective HIV infected group (N = 35) found an association between elevated CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs. 60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS The poor HBV vaccine response rate in the HIV uninfected high-risk adolescents was unexpected and suggests that HBV vaccination doses have not been optimized for older adolescents. This is the first report of decreased responsiveness in HIV infected subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and suggests that ongoing viral replication and concomitant immune system activation decreases the ability of the immune system in HIV infected subjects to respond to vaccination.

Improving Health Outcomes for Youth Living With the Human Immunodeficiency Virus: A Multisite Randomized Trial of a Motivational Intervention Targeting Multiple Risk Behaviors

OBJECTIVE To determine if Healthy Choices, a motivational interviewing intervention targeting multiple risk behaviors, improved human immunodeficiency virus (HIV) viral load. DESIGN A randomized, 2-group repeated measures design with analysis of data from baseline and 6- and 9-month follow-up collected from 2005 to 2007. SETTING Five US adolescent medicine HIV clinics. PARTICIPANTS A convenience sample with at least 1 of 3 risk behaviors (nonadherence to HIV medications, substance abuse, and unprotected sex) was enrolled. The sample was aged 16 to 24 years and primarily African American. Of the 205 enrolled, 19 did not complete baseline data collections, for a final sample size of 186. Young people living with HIV were randomized to the intervention plus specialty care (n = 94) or specialty care alone (n = 92). The 3- and 6-month follow-up rates, respectively, were 86% and 82% for the intervention group and 81% and 73% for controls. Intervention Healthy Choices was a 4-session individual clinic-based motivational interviewing intervention delivered during a 10-week period. Motivational interviewing is a method of communication designed to elicit and reinforce intrinsic motivation for change. Outcome Measure Plasma viral load. RESULTS Youth randomized to Healthy Choices showed a significant decline in viral load at 6 months postintervention compared with youth in the control condition (beta = -0.36, t = -2.15, P = .03), with those prescribed antiretroviral medications showing the lowest viral loads. Differences were no longer significant at 9 months. CONCLUSION A motivational interviewing intervention targeting multiple risk behaviors resulted in short-term improvements in viral load for youth living with HIV. Trial Registration clinicaltrials.gov Identifier: NCT00103532.