Poor adherence to antiretroviral therapy (ART) contributes to disease progression and emergence of drug-resistant HIV in youth with perinatally acquired HIV infection (PHIV+), necessitating reliable measures of adherence. Although electronic monitoring devices have often been considered the gold standard assessment in HIV research, they are costly, can overestimate non-adherence and are not practical for routine care. Thus, development of valid, easily administered self-report adherence measures is crucial for adherence monitoring. PHIV+ youth aged 7–16 (n=289) and their caregivers, enrolled in a multisite cohort study, were interviewed to assess several reported indicators of adherence. HIV-1 RNA viral load (VL) was dichotomized into >/≤400 copies/ml. Lower adherence was significantly associated with VL >400 copies/ml across most indicators, including ≥ 1 missed dose in past 7 days [youth report OR=2.78 (95% CI 1.46–5.27)]. Caregiver and combined youth/caregiver reports yielded similar results. Within-rater agreement between various adherence indicators was high for both youth and caregivers. Inter-rater agreement on adherence was moderate across most indicators. Age ≥13 years and living with biological mother or relative were associated with VL > 400 copies/ml. Findings support the validity of caregiver and youth adherence reports and identify youth at risk of poor adherence.
HIV; adherence; antiretroviral; pediatric
Little is known about immune-reconstitution inflammatory syndrome (IRIS) in children in the United States.
LEGACY is a longitudinal cohort study of HIV-infected participants age 0-24 years at enrollment during 2005-2007 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 six months pre- and post-initiation of the first HAART regimen with a virologic response. We defined OI as IRIS if an OI’s incidence increased after HAART initiation. “Responders” were defined as experiencing ≥1 log decline in viral load within six months following HAART initiation.
Among 575 patients with complete chart abstraction, 524 received HAART. Of these 524 patients, 343 were responders, 181 were non-responders, and 86 experienced OI. Responders accounted for 98/124 (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 non-responders. Overall, OI incidences among responders and non-responders were 33.8 and 12.3, respectively (P = 0.002). Responders were more likely to experience herpes simplex, herpes zoster, and CMV, before HAART initiation (all, P<0.05).
We detected few OIs and no IRIS among participants initiating HAART. The unexpectedly higher OI prevalence among responders, mostly occurring before HAART initiation, may have motivated higher adherence by responders and subsequent categorization as a responder.
HIV infection; pediatric; immune reconstitution inflammatory syndrome (IRIS); opportunistic infection; highly active antiretroviral therapy
Live pentavalent human–bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients.
Determine the relationship between food insecurity and CD4 counts and viral suppression among pediatric HIV-positive patients. Food insecurity was assessed by validated survey. CD4 counts and viral load were abstracted from patients’ charts. We used linear regression for the dependent variable of the natural log of CD4 counts and logistic regression for viral suppression, with backward deletion of covariates with p > 0.1. Food insecurity (β = −0.23, 95 % CI [−0.40, −0.01]) was associated with lower CD4 counts and higher odds of incomplete viral suppression (OR = 4.07, 95 % CI [1.02, 13.92]). Food insecurity may adversely impact pediatric HIV outcomes.
Pediatric; HIV; Food security; CD4 count; Viral load
Youth infected with HIV at birth often have sleep disturbances, neurocognitive deficits, and abnormal psychosocial function which are associated with and possibly resulted from elevated blood cytokine levels that may lead to a decreased quality of life. To identify molecular pathways that might be associated with these disorders, we evaluated 38 HIV-infected and 35 uninfected subjects over 18-months for intracellular cytokine levels, sleep patterns and duration of sleep, and neurodevelopmental abilities. HIV infection was significantly associated with alterations of intracellular pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12), sleep factors (total time asleep and daytime sleep patterns), and neurocognitive factors (parent and patient reported problems with socio-emotional, behavioral, and executive functions; working memory-mental fatigue; verbal memory; and sustained concentration and vigilance. By better defining the relationships between HIV infection, sleep disturbances, and poor psychosocial behavior and neurocognition, it may be possible to provide targeted pharmacologic and procedural interventions to improve these debilitating conditions.
pediatric HIV infection; intracellular cytokines; sleep behavior; neurodevelopment; neurocognition; path analysis
Both perinatally and behaviorally infected HIV-positive youth engage in sexually risky behaviors, and a better understanding of the perceptions of these youth and of health care providers regarding disclosure of HIV status and risk reduction would aid in the development of behavioral interventions for such youth.
In spring 2007, some 20 HIV-positive inner-city youth (aged 13–24) and 15 health care providers who work with HIV-infected youth participated in in-depth, semistructured interviews. Youth were recruited at an HIV clinic, AIDS clinics and an AIDS service organization, and had received care from participating providers. Detailed contextual and thematic discourse analysis was performed on interview transcriptions.
Eighteen of the 20 youth had disclosed their HIV status to another individual at least once. Eleven reported being sexually active, and three of these had been perinatally infected. Qualitative analysis revealed four subthemes related to disclosure: stigma and emotions, trust issues, reasons for disclosing and strategies for addressing disclosure. Five subthemes were identifi ed related to sexual risk reduction: dating challenges, attitudes toward condom use, self-effi cacy for condom use negotiation, pregnancy attitudes and sexual risk reduction strategies. Providers reported that access to more engaging and interactive educational tools within the clinic setting could enhance their risk reduction counseling with HIV-positive youth.
HIV-positive youth experience multiple challenges regarding disclosure and sexual risk reduction, and health care providers need innovative tools that can be used in clinic settings to improve adolescents’ skills in reducing risky sexual behavior.
The Tingathe program utilizes community health workers to improve prevention of mother-to-child transmission (PMTCT) service delivery. We evaluated the impact of antiretroviral (ARV) regimen and maternal CD4+ count on HIV transmission within the Tingathe program in Lilongwe, Malawi.
We reviewed clinical records of 1088 mother-infant pairs enrolled from March 2009 to March 2011 who completed follow-up to first DNA PCR. Eligibility for antiretroviral treatment (ART) was determined by CD4+ cell count (CD4+) for women not yet on ART. ART-eligible women initiated stavudine-lamivudine-nevirapine. Early ART was defined as ART for ≥14 weeks prior to delivery. For women ineligible for ART, optimal ARV prophylaxis was maternal AZT ≥6 weeks+sdNVP, and infant sdNVP+AZT for 1 week. HIV transmission rates were determined for ARV regimens, and factors associated with vertical transmission were identified using bivariate logistic regression.
Transmission rate at first PCR was 4.1%. Pairs receiving suboptimal ARV prophylaxis were more likely to transmit HIV (10.3%, 95% CI, 5.5–18.1%). ART was associated with reduced transmission (1.4%, 95% CI, 0.6–3.0%), with early ART associated with decreased transmission (no transmission), compared to all other treatment groups (p = 0.001). No association was detected between transmission and CD4+ categories (p = 0.337), trimester of pregnancy at enrollment (p = 0.100), or maternal age (p = 0.164).
Low rates of MTCT of HIV are possible in resource-constrained settings under routine programmatic conditions. No transmissions were observed among women on ART for more than 14 weeks prior to delivery.
The incidence of asthma and atopic dermatitis (AD) were evaluated in HIV-infected (n=451) compared to HIV-exposed (n=227) but uninfected (HEU) children and adolescents by abstraction from clinical charts. Asthma was more common in HIV-infected compared to HEU children by clinical diagnosis (25% vs. 20%, p = 0.101), by asthma medication use, (31% vs. 22%, p = 0.012), and by clinical diagnosis or both medication use, (34% vs. 25%, p = 0.012). HIV-infected children had a greater risk of asthma compared to HEU children (HR = 1.37, 95% CI: 1.01 to 1.86). AD was more common in HIV-infected than HEU children (20% vs. 12%, p = 0.009)) and children with AD were more likely to have asthma in both cohorts (41% vs. 29%, p = 0.010). HIV-infected children and adolescents in this study had a 30% increased incidence of asthma and AD, a finding critical for millions of HIV-infected children worldwide.
Atopic dermatitis; asthma; pediatric HIV infection; inhaled corticosteroids; protease inhibitors
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.
To assess the characteristics and outcomes of antiretroviral therapy (ART) interruption (TI) in perinatally HIV-infected (PHIV) children.
The Adolescent Master Protocol (AMP) of the Pediatric HIV/AIDS Cohort Study is a prospective cohort study that enrolled 7-16 year old PHIV children between 2007 and 2009 from 15 sites in the US and Puerto Rico.
TI was defined as ART discontinuation for ≥3 months after ≥6 months of continuous ART. Subjects with and without TI were compared. Rates of change (slopes) in CD4+ T-lymphocyte (CD4) count and percentage (%) per month during TI were calculated. Factors related to CD4 slope in univariable analyses were included in multivariable linear regression.
Of 444 eligible AMP subjects, 101 (23%) had at least one TI. Subjects with TI were born in earlier years but were otherwise similar to those without TI. For 81 TI subjects with complete data, the median (range) CD4% and CD4 count slopes were -0.66%/month (-3.54% to +1.34%) and -12.7 cells/mm3 per month (-148 to +31 cells/mm3 per month), respectively. On multivariable linear regression, there was a trend for lower CD4% slope to be associated (p<0.1) with female sex, higher CD4% at TI, and higher peak viral load before TI. Advanced HIV disease stage and numerous ART regimens were more common in TI subjects in the lowest (fastest-declining) CD4% slope quartile.
TIs in PHIV youth are common. During TIs, CD4 values decline on average but with high intersubject variability. Factors predicting CD4 slope during TI need further study.
HIV-1; Children; Adolescents; Perinatal HIV infection; Treatment interruption; CD4+ T cell percentage
The effect of pre-transplant conditioning upon the long-term outcomes of patients receiving hematopoietic stem cell transplantation (HSCT) for severe combined immunodeficiency (SCID) has not been completely determined.
To assess the outcomes of 23 mostly conditioned SCID patients and compare their outcomes to 25 nonconditioned SCID transplanted patients previously reported.
In the present study, we reviewed the medical records of these 23 consecutive mostly conditioned SCID patients transplanted between 1998 and 2007.
Eighteen patients (median age at transplant 10 [range 0.8–108] mo) received haploidentical mismatched related donor, matched unrelated donor, or mismatched unrelated donor transplants, 17 of whom received pretransplant conditioning and one was not conditioned, 13 (72%) engrafted and survive a median of 3.8 [1.8–9.8] yr, 5 of 13 (38%) require IVIG, and 6 of 6 age-eligible children attend school. Of five recipients (median age at transplant 7 [range 2–23] mo) of matched related donor transplants, all 5 engrafted and survive a median of 7.5 [range 1.5–9.5] yr, 1 requires IVIG, and 3 of 3 age-eligible children attend school. Gene mutations were known in 16 cases: IL2γR in 7 patients, IL7αR in 4 patients, RAG1 in 2 patients, ADA in 2 patients, and AK2 in 1 patient. Early outcomes and quality of life of the previous non-conditioned vs. the present conditioned cohorts were not statistically different but longer-term follow-up is necessary for confirmation.
HSCT in SCID patients results in engraftment, long-term survival, and a good quality of life for the majority of patients with or without pre-transplant conditioning.
Hematopoietic stem cell transplantation; graft-versus-host disease; severe combined immunodeficiency; immune reconstitution; primary immunodeficiency; conditioning
Immunoreconstitution of HIV-infected (HIV+) patients after treatment with highly antiretroviral therapy (HAART) appears to provoke inflammatory diseases.
Determine whether HIV+ children on HAART (HIV+ HAART+) have a higher incidence of asthma than HIV+ children not on HAART (HIV+ HAART−).
To investigate this possibility, 2,664 children (193 HIV+, 2,471 HIV−) born to HIV+ women were evaluated for the incidence and prevalence of asthma (i.e., asthma medication use), and change of CD4+ T cell percentage with time.
The HIV+ HAART+ children had higher CD4+ T cell percentages, lower CD8+ T cell percentages, and lower viral burdens than the HIV+ HAART− children (P≤0.05 to P≤0.01). The cumulative incidence of asthma medication use in HIV+ HAART+ children at 13.5 year rose to 33.5% vs. 11.5% in HIV+ HAART− children (hazard ratio=3.34, P=0.01) and was equal to that in the HIV− children. In children born prior to the HAART era, the prevalence of asthma medication use for HIV+ HAART+ children at 11 years of age was 10.4% vs. 3.8% for HIV+ HAART− children (odds ratio=3.38, P=0.02) and was equal to that of the HIV− children. The rate of change of CD4+ T cells (percent/year) around the time of first asthma medication for HIV+ HAART+ vs. HIV+ HAART− children was 0.81 vs. −1.43 (P=0.01).
The increased incidence of asthma in HIV+ HAART+ children may be driven by immunoreconstitution of CD4+ T cells.
This HIV model of pediatric asthma may yield clues to help explain the epidemic of asthma in the general pediatric population.
pediatric HIV infection; CD4+ T cell mediated induction of asthma; HAART-produced immunoreconstitution
To determine if lower levels of hepatitis C virus (HCV)-specific neutralizing antibodies (nAb) are associated with an increased risk of mother-to-child transmission (MTCT) of HCV, anti-HCV nAb titers were assessed in 63 mothers co-infected with HCV and human immunodeficiency virus type 1 (HIV). Among the mothers, 16 transmitted HCV to their infant but no difference was detected between the ability of maternal plasma from transmitters and non-transmitters to neutralize heterologous HCV pseudoparticles (median nAb titer 1:125 vs. 1:100, P=0.23). In the setting of HIV/HCV co-infection, we found no evidence that anti-HCV nAbs are associated with prevention of MTCT of HCV.
HCV; HIV; mother-to-infant transmission; perinatal transmission; hepatitis C virus; neutralizing antibody; HCVpp; MTCT
Adolescents and young adults account for over 10 million HIV infections worldwide. Prevention of secondary transmission is a major concern as many HIV-positive youth continue to engage in risky sexual behavior. This study pilot-tested “+CLICK”, an innovative, web-based, sexual risk reduction intervention for HIV-positive youth as an adjunct to traditional clinic-based, self-management education. The theory-based application, developed for perinatally and behaviorally infected youth 13–24 years of age, provides tailored activities addressing attitudes, knowledge, skills, and self-efficacy related to sexual risk reduction. HIV-positive youth (N = 32) pilot-tested “+CLICK” to assess usability (ease of use, credibility, understandability, acceptability, motivation) and short-term psychosocial outcomes (importance and self-efficacy related to abstinence and condom use) using a single group, pre-/post-test study design in a hospital-based pediatric clinic and community locations. A subsample of participants (n = 20) assessed feasibility for clinic use. Participants were 62.5% female, 68.8% Black, and 28.1% Hispanic. Mean age was 17.8 years (SD = 2.55), 43.8% were infected behaviorally, 56.2% perinatally, and 68.8% were sexually experienced. Usability ratings were high: 84.4% rated the application very easy to use; 93.8% perceived content as trustworthy; 87.5% agreed most words were understandable; 87.5% would use the application again. Short-term psychosocial outcomes indicate a significant increase in condom use self-efficacy (p = 0.008) and positive trends toward importance (p = 0.067) and self-efficacy (p = 0.071) for waiting before having sex. Regarding feasibility, participants accessed “+CLICK” during waiting periods (average time, 15 minutes) in their routine clinic visit. Clinic staff rated “+CLICK” highly in providing consistent, confidential, and motivational sexual health education without significant disruption to clinic flow. Results suggest that the application is a feasible tool for use in the clinic and has the potential to affect psychological antecedents to sexual behavior change. Further research on long-term and behavioral effects is indicated prior to broader dissemination into clinical practice.
HIV-positive; youth; computer-based interventions; behavioral interventions; self-management training
Human immunodeficiency virus-infected women (n = 16) received indinavir (800 mg three times a day) plus zidovudine plus lamivudine from 14 to 28 weeks of gestation to 12 weeks postpartum. Two women and eight infants experienced grade 3 or 4 toxicities that were possibly treatment related. Indinavir area under the plasma concentration-time curve was 68% lower antepartum versus postpartum, suggesting increased intestinal and/or hepatic CYP3A activity during pregnancy.