Thirty-year Perspective of the Long-term Survival, CD4 Percentage and Social Achievements of Perinatally HIV-infected Children as a Function of Their Birth Era.

BACKGROUND: Pediatric HIV has evolved from a pre-antiretroviral (ART) era (pre-1989 or pre-ART) to an ART era (1989 to 1996) and to a highly active antiretroviral therapy (HAART) era (post-1996). As we have passed the third decade following these individuals, we thought it useful to review clinical, laboratory and social outcomes. METHODS: A retrospective, cross-sectional study of 399 children infected perinatally. They were divided into pre-ART, ART and HAART groups. A Kaplan-Meier plot was constructed. One hundred seventy-nine have been lost to follow-up at an average of 7.6 (0.3-27.6) years. RESULTS: Approximately 40%, 80% and 90% of individuals in the pre-ART, ART and HAART groups have long-term survival. One hundred twenty-one died at an average of 5.1 (0-26.1) years. Pre-ART, ART and HAART groups had mean most recent CD4% values (±SEM) of 16.74 (1.09), 22.97 (0.96) and 33.07 (2.09), respectively (P < 0.001). Pre-ART RNA is limited in that era and present if they survived to another era. In this group, the median RNA values in those who died (311,300, n = 16) was greater than in survivors (19,402, n = 45). Forty-three percent of the individuals in the ART group and 77% of individuals in the HAART group had most recent HIV RNA <400 copies/mL. Eighteen individuals >18 years of age have only a grade school or no education. Fifty-five have graduated high school or received an equivalency diploma. Twenty-three more have completed college. Nadir and recent CD4% of those who did and did not complete high school was equivalent to college graduates. Sixteen survivors (1/2 male) have had 18 uninfected children. CONCLUSIONS: This first long-term follow-up study demonstrates remarkable survival and social skills of our patients.

Negative life events and depression in adolescents with HIV: a stress and coping analysis.

The prevalence of negative life events (NLE) and daily hassles, and their direct and moderated associations with depression, were examined among HIV-infected adolescents. Specifically, we examined whether the negative association with depression of NLE, daily hassles, and/or passive coping were moderated by social support or active coping strategies. Demographic characteristics, depression, coping, social support, NLE, and daily hassles were collected at baseline as part of the Adolescent Impact intervention via face-to-face and computer-assisted interviews. Of 166 HIV-infected adolescents, 53% were female, 72.9% black, 59.6% with perinatally acquired HIV (PIY), the most commonly reported NLE were death in family (81%), violence exposure (68%), school relocation (67%), and hospitalization (61%); and for daily hassles "not having enough money (65%)". Behaviorally infected youth (BIY--acquired HIV later in life) were significantly more likely to experience extensive (14-21) lifetime NLE (38.8% vs. 16.3%, p < .012) than PIY. In multiple stepwise regression analysis, the model accounting for the greatest variability in depression scores (32%) included (in order of entry): daily hassles, low social support, behaviorally acquired HIV, minority sexual orientation, and passive coping. A significant passive coping-by-social support interaction revealed that the association between passive coping and depression was exacerbated when social support was low. Social support moderated the effect of NLE, such that NLE were associated with greater depression when social support was low, although the effect did not remain statistically significant when main effects of other variables were accounted for. Daily hassles, poor coping, and limited social support can adversely affect the psychological well-being of HIV-infected adolescents, particularly sexual minority youth with behaviorally acquired HIV. Multimodal interventions that enhance social support and teach adaptive coping skills may help youth cope with environmental stresses and improve mental health outcomes.

Prevalence and correlates of violence exposure among HIV-infected adolescents.

Violence exposure among HIV-infected adolescents was estimated using Poisson regression and adjusted event rate ratios (ERR). Of 166 urban adolescents (99 perinatally infected youth [PIY]; 67 behaviorally infected youth [BIY]) 52.5% (n = 85) experienced violence; 79% (n = 131) witnessed violence. Sexual violence was experienced by 18% (6 PIY, 24 BIY) before age 13 years and by 15% (6 PIY, 19 BIY) during adolescence. BIY were significantly more likely than PIY to have experienced and witnessed violence. Controlling for transmission, ever-bartered sex (ERR = 1.92, CI [1.31 to 2.81], p = .009) and family disruptions (ERR = 1.19, CI [1.03 to 1.39], p = .022) were associated with violence victimization. Family disruptions (ERR = 1.17, CI [1.05 to 1.30], p = .004), female gender (ERR = 1.32, CI [1.05 to 1.66], p = .017), and heterosexual orientation (ERR = 1.48, CI = [1.11 to 1.97], p = .006) were associated with witnessing violence.

Prevalence and predictors of drug use among adolescents with HIV infection acquired perinatally or later in life.

We examined the prevalence and predictors of drug use among a diverse group of adolescents living with HIV infection acquired perinatally or through sexual risk behaviors ("behaviorally acquired"). Adolescents ages 13-21 (n = 166) who were receiving care at one of five pediatric/adolescent HIV clinics in three US cities (Baltimore MD, Washington DC, and New York NY) and were enrolled in a behavioral intervention were interviewed at baseline regarding lifetime drug use experiences and depression symptoms. A majority of study participants reported using alcohol (57.2%) and marijuana (51.2%); 48.8% reported tobacco/cigarette use. The mean age of onset of use for each type of drug was 14 years or younger. A larger proportion of participants with behaviorally acquired HIV than adolescents with perinatally acquired HIV reported lifetime use of alcohol (76.1 vs. 44.4%), marijuana (73.1 vs. 36.4%), tobacco (70.2 vs. 34.3%), and club drugs (22.4 vs. 3%) (all p < 0.001).

Predictors of antiretroviral medication adherence among a diverse cohort of adolescents with HIV.

PURPOSE: To compare prevalence and describe predictors of antiretroviral treatment adherence among adolescents with HIV acquired perinatally (PIY) or through risk behaviors (BIY). METHODS: Data were obtained from the baseline assessment of Adolescent Impact, an intervention for HIV-infected adolescents receiving care in three U.S. cities. Patients self-reported missed medication doses as well as medication factors, HIV knowledge, disclosure, substance use, mental health, and social support through face-to-face or computer-assisted interviews. RESULTS: Of 104 participants, 68 (65.4%) reported full adherence. Compared with BIY, PIY were younger, had greater HIV disease severity, and had more structural supports. Adjusting for transmission mode (PIY vs. BIY), nonadherence by self-report was associated with higher viral load (VL) (adjusted odds ratio [AOR] = 1.5, confidence interval [CI] = 1.03, 2.18). Nonadherent adolescents were significantly likely to have had AIDS, discussed HIV disease with providers, reported difficulty with medication routine, experienced internalizing behavior problems, and used drugs. In multivariate analyses, independent predictors of nonadherence included acquiring HIV behaviorally (AOR = 4.378, CI = 1.055, 18.165), ever having AIDS (AOR = 4.78, CI = 1.31, 17.49), perceiving difficult medication routine (AOR = 1.84, CI = 1.07, 3.16), discussing disease indicators with provider (AOR = 4.57, CI = 1.74, 11.98), and missing doses because of forgetting (AOR = 2.53, CI = 1.29, 4.96). Adjusting for transmission mode, detectable VL was associated with lower recent CD4(+) lymphocyte counts, discussing disease indicators with providers, and missing doses because of forgetting or being depressed. Low recent CD4(+) lymphocyte counts (AOR = .988, p = .024) but fewer HIV symptoms (AOR = .466, p = .032) and missing doses because of forgetting (AOR = 1.76, p = .05) were independently associated with detectable VL in multivariate analysis. CONCLUSIONS: Despite differences between groups, nonadherence was associated with severity of illness, difficult medication routine, and forgetfulness. Beyond individual needs, both groups of adolescents had suboptimal adherence and would benefit from simplified medication routines and organizational skills.

A multimodal behavioral intervention to impact adherence and risk behavior among perinatally and behaviorally HIV-infected youth: description, delivery, and receptivity of adolescent impact.

Secondary prevention programs are needed to help HIV-positive youth reduce risk behavior and improve adherence to HIV medications. This article provides an overview of Adolescent Impact, a secondary HIV prevention intervention, including its description, delivery, and receptivity among the two unique groups of participants. Adolescent Impact, a 12-session behavioral intervention incorporating individual and group components was designed to increase HIV knowledge, disease management and risk reduction skills, and motivate healthy lifestyles among HIV-infected adolescents. A standardized protocol was implemented at three sites in the northeastern United States. One hundred sixty-six HIV-positive youth, aged 13-21 (mean = 16.8 years), enrolled in the study were randomized to receive either the intervention (n = 83) or standard of care (n = 83). Participants were predominantly of minority race/ethnicity (94% African American or Hispanic); 53% were female and 59.6% were perinatally infected. Perinatally infected youth were significantly more likely to be young, had experienced HIV Class C-related symptoms and had CD4-positive T lymphocyte counts of fewer than 200 cells (all p values < .01). The mean number of sessions attended was 9.4, with most (83.3%) participants attending at least half (≥ 6) of the intervention sessions (86% perinatally infected, 78.6% behaviorally infected, p = .5). Participants' sociodemographic and clinical characteristics mirrored those of the larger HIV adolescent cohort in the United States Relatively high attendance rates suggest that youth were receptive to the program and its content. Through use of multiple intervention modalities, Adolescent Impact was able to accommodate a diverse group of clinic-attending HIV-positive youth and address the need for a compact intervention for use in the clinical setting.

Safety and immunogenicity of early measles vaccination in children born to HIV-infected mothers in the United States: results of Pediatric AIDS Clinical Trials Group (PACTG) protocol 225.

UNLABELLED: BACKGROUND.: ACTG (Pediatric AIDS Clinical Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus-infected (HIV-infected) (POS) and uninfected (NEG) children in the pre-highly active antiretroviral therapy (pre-HAART) period. METHODS: Plaque-reduction neutralization (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (∼3 years of age). RESULTS: The 110 subjects included: 65 2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n=175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n=2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers ≥120 mIU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mIU/mL, respectively; P=.023). At ∼3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers ≥120 mIU/mL. Prevaccination titers ≥25 mIU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers ≥120 mIU/mL (56% vs 90%; P=.004). CONCLUSIONS: Among HIV-infected children pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children.

Sexual transmission risk behavior of adolescents With HIV acquired perinatally or through risky behaviors.

OBJECTIVE: To describe the prevalence and predictors of the transmission-related behaviors of adolescents with HIV acquired perinatally (perinatal) or through risky behaviors (behavioral). METHODS: HIV-positive adolescents (n = 166) aged 13-21, receiving care in 3 US cities, reported sexual behaviors, drug use, and psychosocial and demographic characteristics. HIV-related data were abstracted from medical records. RESULTS: Of 105 sexually experienced adolescents reporting risk history (42 perinatal, 63 behavioral), 49 had engaged in unprotected sex since learning their diagnosis (12 perinatal, 37 behavioral). Of sexually experienced girls, 19 had been pregnant (5 of 24 perinatal, 14 of 31 behavioral). Risk information was provided for 115 of 132 recent sex partners, 61 of whom had unprotected sex with study participants (10 with 8 perinatal participants; 51 with 33 behavioral participants). Recent unprotected sex was associated with sexual abuse during adolescence (adjusted odds ratio = 9.61, 95% CI: 1.07 to 86.12) and greater HIV knowledge (adjusted odds ratio = 1.29, 95% CI: 1.00 to 1.66) when transmission category, age, and sexual orientation were controlled. CONCLUSIONS: To limit HIV transmission and prevent unplanned pregnancies, developmentally appropriate risk-reduction interventions, and screening and treatment referral for sexual abuse, must be integrated into the care of both perinatally and behaviorally HIV-infected adolescents.

Characterizing social support: global and specific social support experiences of HIV-infected youth.

This study examined the nature, type, and source of social support available to a diverse group of HIV-infected adolescents and the relationship between social support and depression. Data were obtained from the baseline assessment of Adolescent Impact, a behavioral intervention conducted in 2003-2006 involving 166 HIV-infected youth, ages 13-21, in care at four urban medical centers. Youth completed the Medical Outcomes Study Social Support Survey, Beck Depression Inventory, and questions about HIV-specific social support including locus (family and friends) and type (structural, perceived, instrumental, and satisfaction). Linear regression modeling examined the relation between HIV-specific and general perceived social support, and between social support and depression. Participants were predominately minority (72% black and 20% Hispanic); perinatally infected (60% PIY), and female (53%). Most had someone to either remind them to attend (71%) or to bring them to clinic (60%), a majority family (53%) and fewer friends (4%). More youth reported being satisfied with family (64%) social support than that from friends (51%). Behaviorally infected youth (BIY) had significantly more friends who knew their serostatus than PIY (means = 4.5 and 1.7; p < 0.001), but received significantly less help from family in accessing care (p < 0.001). Satisfaction with family social support was the best predictor of general perceived social support with general perceived social support and behavioral mode of transmission the best predictors of depression. Regular screening of HIV-positive youth for social support needs, especially BIY, and identification of sources for social support should be a regular part of care.

Natural history of HIV infected pediatric long-term or slow progressor population after the first decade of life.

BACKGROUND: Perinatally infected long-term nonprogressors/slow progressors represent a select group of individuals. There is very limited information on this group of children beyond the first decade of life. A group of HIV-infected long-term nonprogressor/slow progressor children was studied. METHODS: We enrolled 20 HIV-infected adolescents who were receiving no or minimal therapy (defined as single or dual nucleoside therapy) before the age of 10 years and who had maintained CD4 counts above 25% for the first decade of life. We analyzed immunologic and virologic characteristics. Thymic receptor excision circles (TREC) were measured on stored frozen peripheral blood mononuclear cells. CD4 count, viral load and other pertinent information including race and age were obtained from individual medical records. RESULTS: Nine of the 20 patients recruited were noted to have developed falling CD4 counts at or around puberty, whereas the other 11 remained stable. There was no difference in TREC values or HIV RNA values before or after puberty between the 2 groups of patients. Those who remained stable, in terms of maintaining CD4 T cells as a group had falling viral loads with age. Those whose CD4 values declined after puberty had viral loads that did not decrease with age. CONCLUSION: A select group of patients who never received HAART during their first decade of life will continue to maintain good CD4 associated with declining HIV RNA values. Thymic output is not predictive of those that don't maintain CD4 T cells.

Correlation between HIV-Specific CD8 cell production of interferon- gamma and plasma levels of HIV RNA in perinatally infected pediatric populations.

BACKGROUND: CD8 cell responses to human immunodeficiency virus (HIV) have been correlated with virus control in adults, and this study outcome has been controversial. Attempts to establish the same correlation in small numbers of children have also been made, with similar controversy resulting. METHODS: A total of 110 perinatally infected children were studied. Nine of the children (mean age, 1.9 years vs. 11.8 years for the remaining 101 children) received treatment with antiretrovirals within the first 3 months of life. CD4 cell and HIV RNA levels were measured. Production of interferon- gamma after exposure to recombinant vaccinia vectors was measured by enzyme-linked immunospot (ELISPOT) assay. RESULTS: Responses to Pol and Gag antigens exceeded those to Nef and Env antigens, with responses significantly approximated by a quadratic function for which peak responses occurred at plasma HIV RNA levels of 103-104 HIV RNA copies/mL. Children who are treated early in life with highly active antiretroviral therapy have fewer total responses of ELISPOT-forming cells to HIV antigens than do children who are treated later in life.

Immunoreconstitution in children receiving highly active antiretroviral therapy depends on the CD4 cell percentage at baseline.

The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load.