Meningococcal Conjugate and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccination Among HIV-infected Youth.

BACKGROUND: The meningococcal conjugate vaccine (MCV4) and the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) were first recommended for adolescents in the US in 2005. The goal of our study was to determine MCV4 and Tdap vaccines coverage among perinatally and behaviorally HIV-infected adolescents in 2006 and to compare coverage estimates in our study population to similarly aged healthy youth in 2006. METHODS: Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) is a retrospective cohort study of HIV-infected youth in 22 HIV specialty clinics across the US. Among LEGACY participants ≥11 years of age in 2006, we conducted a cross-sectional analysis to determine MCV4, Tdap and MCV4/Tdap vaccine coverage. We compared vaccine coverage among our study population to coverage among similarly aged youth in the 2006 National Immunization Survey for Teens (NIS-Teen Survey). Multivariable mixed effects logistic regression modeling was used to examine associations between MCV4/Tdap vaccination and mode of HIV transmission. RESULTS: MCV4 and Tdap coverage rates among 326 eligible participants were 31.6% and 28.8%, respectively. Among adolescents 13-17 years of age, MCV4 and Tdap coverage was significantly higher among HIV-infected youth than among youth in the 2006 NIS-Teen Survey (P <0.01). In multivariable analysis, perinatally HIV-infected youth were significantly more likely to have received MCV4/Tdap vaccination compared with their behaviorally infected counterparts (adjusted odds ratio: 5.1; 95% confidence interval: 2.0, 12.7). HIV-infected youth with CD4 cell counts of 200-499 cells/µL were more likely to have had MCV4/Tdap vaccination compared with those with CD4 counts ≥500 cells/µL (adjusted odds ratio: 2.2; 95% confidence interval: 1.2, 4.3). Participants with plasma HIV RNA viral loads of >400 copies/mL were significantly less likely to have received MCV4/Tdap vaccination (P < 0.05). CONCLUSIONS: MCV4 and Tdap coverage among HIV-infected youth was suboptimal but higher than for healthy adolescents in the 2006 NIS-Teen Survey. Perinatal HIV infection was associated with increased likelihood of vaccination. Specific measures are needed to improve vaccine coverage among adolescents in the US.

Perinatal HIV Prevention Outcomes in U.S.-Born Versus Foreign-Born Blacks, PSD Cohort, 1995-2004.

We examined differences in HIV-infected U.S.-born and foreign-born black mothers who delivered perinatally HIV-exposed and -infected children during 1995-2004 in the Pediatric Spectrum of HIV Disease Project, a longitudinal cohort study. Prevalence ratios were calculated to explain differences in perinatal HIV prevention opportunities comparing U.S.-born to foreign-born and African-born to Caribbean-born black mothers. U.S.-born compared with foreign-born HIV-infected black mothers were significantly more likely to have used cocaine or other non-intravenous illicit drugs, exchanged money or drugs for sex, known their HIV status before giving birth, received intrapartum antiretroviral (ARV) prophylaxis, and delivered a premature infant; and were significantly less likely to have received prenatal care or delivered an HIV-infected infant. African-born compared with Caribbean-born black mothers were more likely to receive intrapartum ARV prophylaxis. These differences by maternal geographical origin have important implications for perinatal HIV transmission prevention, and highlight the validity of disaggregating data by racial/ethnic subgroups.

Prevalence and outcomes of recycling NNRTIs despite documented NNRTI resistance in HIV-infected children and youth.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly used in pediatric patients; however, rapid development of resistance, due to non-adherence and cross-resistance, results in their discontinuation and limits their recycling. We evaluated the clinical experience of recycling NNRTIs despite documented NNRTI resistance (NNRTI-R), and examined virologic and CD4 cell count outcomes among participants enrolled in Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY), a national HIV-infected pediatric cohort. We conducted a retrospective analysis of LEGACY participants with major NNRTI-R. Using chi-square analyses and logistic regression, we examined demographic and clinical factors associated with prescription of NNRTIs despite documented NNRTI-R, and associated changes in plasma HIV RNA viral load and CD4 cell counts. Sixteen of 133 (12%) participants with documented NNRTI-R re-started NNRTIs for a median of 370 days (IQR 105-919) with a median 402 days (IQR 70-841) between documentation of NNRTI-R to NNRTI recycling. Participants recycling NNRTIs were less likely to have documented past non-adherence (40.0% vs. 69.2%; p = 0.02). Among twelve patients with virologic data at 24 (± 8) weeks; seven (58.3%) experienced virologic suppression while on the recycled NNRTI-based regimens. Of the five who failed to suppress, three with subsequent genotyping developed additional NNRTI-R mutations compromising higher generation NNRTIs. While NNRTI's were recycled in only a small fraction of LEGACY participants harboring NNRTI-R mutations, such recycling increased the risk of inducing further resistance mutations that compromised use of higher generation NNRTIs.

Use of nucleoside reverse transcriptase inhibitor-only regimens in HIV-infected children and adolescents.

OBJECTIVE: In adults, nucleoside reverse transcriptase inhibitor-only antiretroviral regimens (NOARs) with ≥3 nucleoside reverse transcriptase inhibitors are less potent than highly active antiretroviral therapy (HAART). Published pediatric experience with NOARs is limited; thus, we wished to better define the virological, immunological and toxicological effects of NOARs in children and adolescents. METHODS: We analyzed data from NOAR-treated participants in LEGACY, a multicenter observational cohort study of HIV-infected children and adolescents. NOAR-treated case-participants were matched to participants without prior NOAR who initiated HAART during the same year for comparison. RESULTS: Of 575 participants with data from time of HIV diagnosis through 2006, 67 (12%) received NOARs for at least 24 weeks; most (46%) received the fixed dose combination of zidovudine/lamivudine/abacavir. NOAR use peaked in 2001 to 2002. NOAR-treated participants were significantly older and more treatment experienced than HAART-treated participants. Virologic outcomes, including the percentage of participants with a plasma HIV RNA viral load <400 copies/mL at week 24 (47% versus 34%) and the mean 24-week change in log10 plasma HIV RNA viral load from baseline (-0.63 versus -1.02), were similar between NOAR- and HAART-treated participants, but virologic rebound was more likely in NOAR-treated participants (77% versus 54%, P = 0.02). Increase in CD4 percentage points from baseline to 24 weeks was negligible in NOAR-treated participants compared with HAART-treated participants (0.95% versus 10.1%, P < 0.001). Anemia and leukopenia were more commonly reported with NOARs than HAART. DISCUSSION: Week 24 virologic outcomes were similar between NOAR- and HAART-treated participants, but NOAR durability was poorer and their use was associated with less immunologic reconstitution. NOARs should play a limited role in pediatric and adolescent antiretroviral therapy.

Incidence of opportunistic illness before and after initiation of highly active antiretroviral therapy in children.

BACKGROUND: Little is known about immune reconstitution inflammatory syndrome in children in the United States. METHODS: LEGACY is a longitudinal cohort study of HIV-infected participants 0-24 years at enrollment during 2005 to 2007 from 22 US clinics. For this analysis, we included participants with complete medical record abstraction from birth or time of HIV diagnosis through 2006. Opportunistic illness (OI) included AIDS-defining conditions and selected HIV-related diagnoses. We calculated the incidence (#/100 patient-years) of OI diagnosed in the months pre- and postinitiation of the first highly active antiretroviral therapy (HAART) regimen which was followed by ≥1 log reduction in HIV viral load. We defined OI as immune reconstitution inflammatory syndrome if an OI incidence increased after HAART initiation. "Responders" were defined as experiencing ≥1 log decline in viral load within 6 months after HAART initiation. RESULTS: Among 575 patients with complete chart abstraction, 524 received HAART. Of these 524 patients, 343 were responders, 181 were nonresponders and 86 experienced OI. Responders accounted for 98 of 124 (79%) of OI. Pre-HAART and post-HAART OI incidences were 43.7 and 24.4 (P = 0.003), respectively, among responders and 15.9 and 9.1 (P = 0.2), respectively, among nonresponders. Overall, OI incidences among responders and nonresponders were 33.8 and 12.3, respectively (P = 0.002). Responders were more likely than nonresponders to experience herpes simplex and herpes zoster before HAART initiation (all, P < 0.002). CONCLUSIONS: The lack of immune reconstitution inflammatory syndrome in participants initiating HAART may be due to low overall OI rates. The unexpectedly higher OI prevalence comprised mainly of herpes simplex and zoster, before HAART initiation among responders, may have motivated them to better adhere to HAART.

Methicillin-Resistant Staphylococcus aureus Infections in Human Immunodeficiency Virus-Infected Children and Adolescents.

Background. Methicillin-resistant Staphylococcus aureus (MRSA) infection incidence has increased in healthy US children. Our objective was to evaluate MRSA incidence and correlates in HIV-infected youth. Methods. The CDC-sponsored LEGACY study is a US multicenter chart abstraction study of HIV-infected youth. We identified MRSA infections among participants with ≥1 visit during 2006. We used bivariate and multivariable analyses to compare sociodemographic and HIV clinical factors between MRSA cases and noncases. Results. Fourteen MRSA infections (1 invasive, 12 soft tissue, 1 indeterminate) occurred among 1,813 subjects (11.1 infections/1,000 patient-years (PY), 95% CI: 11.06-11.14). Most (86%) isolates were clindamycin susceptible. Compared with noncases, MRSA cases were more likely older (17 versus 14 years), black (100% versus 69%), behaviorally HIV infected (43% versus 17%), and in Maryland (43% versus 7%) and had viral loads (VL) >1000 copies/mL (86% versus 51%) and lower mean CD4% (18% versus 27%) (all P < 0.05). In multivariate analysis, independent risk factors were Maryland care site (adjusted odds ratio (aOR) = 9.0), VL >1000 copies/mL (aOR = 5.9), and black race (aOR undefined). Conclusions. MRSA occurred at a rate of 11.1 infections/1,000 PY in HIV-infected youth but invasive disease was uncommon. Geographic location, black race, and increased VL, but not immunosuppression, were independently associated with MRSA risk.

Cervical pap screening cytological abnormalities among HIV-infected adolescents in the LEGACY cohort.

OBJECTIVES: To determine the prevalence of cervical Pap screening (CPAP-S), identify factors associated with CPAP-S, and explore risk factors for abnormal cervical cytology in female adolescents with perinatally and behaviorally acquired HIV infection. DESIGN: Cross-sectional. SETTING: LEGACY is a national observational cohort chart review study of 1478 HIV-infected persons (

Associations of medically documented psychiatric diagnoses and risky health behaviors in highly active antiretroviral therapy-experienced perinatally HIV-infected youth.

The Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) study is a prospective, multisite, longitudinal cohort of U.S. HIV-infected youth. This analysis was limited to perinatally HIV-infected youth (n=197), 13 years and older, with selected variables completely abstracted from HIV diagnosis through 2006. We evaluated relationships between ever having one or more nonsubstance related medically documented psychiatric diagnoses and three risky health behaviors (substance abuse, preadult sexual activity, and treatment adherence problems) recorded between 2001 and 2006. Logistic regression was used for all binary outcomes and participant age was included as a covariate when possible. All 197 participants included in the analysis were prescribed antiretroviral therapy during the study period; 110 (56%) were female, 100 (51%) were black non-Hispanic, and 86 (44%) were Hispanic; mean age at the last visit was 16.8 years, ranging from 13 to 24 years. One hundred forty-six (74%) participants had a history of at least one risky health behavior. There were 108 (55%) participants with at least one medically documented psychiatric diagnosis, 17 (9%) with at least one record of substance abuse, 12 (6%) with documented preadult sexual activity, and 142 (72%) participants with reported adherence problems. In the final model, a history of at least one psychiatric diagnosis was associated with having at least one of the three risky behaviors (odds ratio [OR]=2.33, p=0.015). There is a need for a continued close partnership between HIV specialty care providers and mental health services treating perinatally HIV-infected youth with an added focus on improving treatment adherence.

Correlates of sexual activity and sexually transmitted infections among human immunodeficiency virus-infected youth in the LEGACY cohort, United States, 2006.

BACKGROUND: To determine the prevalence and correlates of sexual activity and sexually transmitted infections (STIs) among human immunodeficiency virus (HIV)-infected youth. METHODS: The Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) is an observational medical record study of perinatally and behaviorally HIV-infected (PHIV and BHIV) youth followed at 22 US HIV clinics. PHIV youth were HIV infected at birth or by breast-feeding. BHIV youth were HIV infected sexually or by injection drug use. We determined the prevalence of sexual activity during 2006 and examined correlates of sexual activity among 13- to 24-year-old PHIV youth using multivariable generalized linear models. Among sexually active persons, we determined the association between mode of HIV acquisition and non-HIV STI diagnosis using multivariable generalized linear models. RESULTS: In all, 34% (195/571) of PHIV and 89% (162/181) of BHIV youth were sexually active. Eighty percent (155/195) of sexually active PHIV youth reported ever using condoms. Ninety-three percent discussed sex with a health care provider. Increasing age (adjusted prevalence ratio [APR]: 1.17 per year of age, 95% confidence interval [CI] = 1.12-1.23), having a boyfriend/girlfriend (APR: 2.74, 95% CI = 1.75-4.29), and injection drug use (APR: 1.38, 95% CI = 1.06-1.79) correlated with sexual activity after adjusting for socio-demographic and HIV-related clinical variables. Among sexually active youth, after adjusting for relevant confounders, PHIV youth were less likely than BHIV youth to have been diagnosed with an STI in 2006 (APR: 0.25, 95% CI = 0.13-0.46). CONCLUSIONS: Sexual activity among HIV-infected adolescents is common. Factors associated with sexual activity in this study should be taken into account in developing behavioral risk reduction interventions targeting PHIV youth.

Declines in low birth weight and preterm birth among infants who were born to HIV-infected women during an era of increased use of maternal antiretroviral drugs: Pediatric Spectrum of HIV Disease, 1989-2004.

OBJECTIVE: Our goal was to determine trends in low birth weight and preterm birth among US infants born to HIV-infected women. METHODS: We used data from the longitudinal Pediatric Spectrum of HIV Disease, a large HIV cohort, to assess trends in low birth weight and preterm birth from 1989 to 2004 among 11,321 study infants. Among women with prenatal care, we also assessed risk factors, including maternal antiretroviral therapy during pregnancy, that were predictive of low birth weight and preterm birth using univariate and multivariate logistic regression models. RESULTS: Overall, 11,231 of 14,464 infants who were enrolled in Pediatric Spectrum of HIV Disease were tested during the neonatal period. From 1989 to 2004, testing increased from 32% to 97%. The proportion of HIV-exposed infants who had low birth weight decreased from 35% to 21% and occurred in all racial/ethnic groups. Prevalence of preterm birth decreased from 35% to 22% and occurred in all groups. Any maternal antiretroviral therapy use increased from 2% to 84%. Among 8793 women who had prenatal care, low birth weight was associated with a history of illicit maternal drug use, unknown maternal HIV status before delivery, symptomatic maternal HIV disease, black race, Hispanic ethnicity, and infant HIV infection. Antiretroviral therapy or lack of it was not associated with low birth weight. Among women with prenatal care, preterm birth was associated with a history of illicit maternal drug use, symptomatic maternal HIV disease, no antiretroviral therapy, receipt of a 3-drug highly active antiretroviral therapy regimen with protease inhibitors, black race, and infant HIV infection. CONCLUSIONS: The proportion of infants who had low birth weight or were born preterm declined during an era of increased maternal antiretroviral therapies. These Pediatric Spectrum of HIV Disease trends differ from the overall increases in both outcomes among the US population.

Updated estimates of healthcare utilization and costs among perinatally HIV-infected children.

OBJECTIVES: This study examined changes in healthcare use among perinatally HIV-infected children and developed new estimates of expected lifetime treatment costs. METHODS: The study analyzed longitudinal medical record data from the Pediatric Spectrum of Disease study on perinatally HIV-infected children enrolled in 6 US sites during 1995 and 2001 for enrollee characteristics including healthcare utilization. For the year 2001, costs were assigned to hospitalization, HIV-related drug usage, and laboratory testing. To estimate lifetime treatment costs based on those categories, median survival times of 9, 15, and 25 years were assumed and average annual healthcare utilization costs were applied to each year of survival. RESULTS: From 1995 to 2001, hospitalization rates fell from 0.67 per child-year to 0.23 per child-year (P < 0.05). In 2001, the average cost of healthcare utilization per child was $12,663, including $2164 for hospitalization, $9505 for HIV-related drugs, and $994 for laboratory tests. The discounted lifetime treatment cost, based on those 3 cost categories, was $113,476 for 9 years of survival, $151,849 for 15 years, and $228,155 for 25 years. CONCLUSIONS: Hospitalizations among perinatally HIV-infected children decreased significantly from 1995 to 2001. Compared with previously published estimates, lifetime treatment costs for children perinatally infected with HIV have remained relatively stable. However, as years of survival increase for this population, lifetime costs also are likely to increase.