Murli Purswani

Early Archiving and Predominance of Nonnucleoside Reverse Transcriptase Inhibitor—Resistant HIV-1 among Recently Infected Infants Born in the United States

BACKGROUND The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. METHODS We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4(+) T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. RESULTS Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4(+) T cell latent reservoir in all 5 infants. CONCLUSIONS The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials.

Increased risk of asthma and atopic dermatitis in perinatally HIV-infected children and adolescents.

The incidence of asthma and atopic dermatitis (AD) was 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 and/or 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 an increased incidence of asthma and AD, a finding critical for millions of HIV-infected children worldwide.

Identifying future VFR travelers among immigrant families in the Bronx, New York.

Travelers visiting friends and relatives (VFR) have low rates of pre-travel health encounters. In 2006 in the Bronx, New York, a convenience sample of 129 families originating in malaria-endemic countries and presenting for a routine pediatric outpatient evaluation completed a standardized questionnaire regarding future travel plans to their country of origin. Pro-active screening for intended travel activities can identify future VFR travelers and ascertain potentially high-risk itineraries, thereby enabling education regarding the importance of accessing competent pre-travel medicine services.

Antiretroviral Drug Resistance Among Children and Youth in the United States With Perinatal HIV

Among 234 US youths with perinatal human immunodeficiency virus, 75% had antiretroviral resistance, substantially higher than that of the reference laboratory overall (36%-44%). Resistance to newer antiretrovirals and to all antiretrovirals in a class was uncommon. The only factor independently associated with future resistance was a higher peak viral load.

Human Immunodeficiency Virus Type 1 DNA Decay Dynamics With Early, Long-term Virologic Control of Perinatal Infection

Background. Early antiretroviral therapy (ART) limits proviral reservoirs, a goal for human immunodeficiency virus type 1 (HIV-1) remission strategies. Whether this is an immediate or long-term effect of virologic suppression (VS) in perinatal infection is unknown. Methods. We quantified HIV-1 DNA longitudinally for up to 14 years in peripheral blood mononuclear cells (PBMCs) among 61 perinatally HIV-1-infected youths in the Pediatric HIV/AIDS Cohort Study who achieved VS at different ages. Participants in group 1 (n = 13) were <1 year of age and in group 2 (n = 48) from 1 through 5 years of age at VS. Piecewise linear mixed-effects regression models assessed the effect of age at VS on HIV-1 DNA trajectories during VS. Results. In the first 2 years following VS, HIV-1 DNA levels decreased by -0.25 (95% confidence interval [CI], -.36 to -.13) log10 copies/million PBMCs per year and was faster with early VS by age 1 year compared with after age 1 (-0.50 and -0.15 log10 copies/million PBMCs per year, respectively). Between years 2 and 14 from VS, HIV-1 DNA decayed by -0.05 (95% CI, -.06 to -.03) log10 copies/million PBMCs per year and was no longer significantly different between groups. The estimated mean half-life of HIV-1 DNA from VS was 15.9 years and was shorter for group 1 compared to group 2 at 5.9 years and 18.8 years, respectively (P = .09). Adjusting for CD4 cell counts had no effect on decay estimates. Conclusions. Early effective, long-term ART initiated from infancy leads to decay of HIV-1-infected cells to exceedingly low concentrations desired for HIV-1 remission strategies.

Dermatological conditions in international pediatric travelers: Epidemiology, prevention and management

With an increasing number of children traveling internationally, there has been growing interest in studying the burden of travel-associated illnesses in children. We reviewed recently published (2007-2012) studies on travel-associated illness in children, and extracted the reported spectrum of dermatological conditions in children. Dermatologic problems are among the leading health concerns affecting children during and after return from international travel. Most are mild and self-limited, but an extended spectrum of conditions has been reported from a large retrospective multicenter study. Children may be especially at risk for infections related to environmental exposures, arthropod-related problems, and animal bites. Of note are also tropical and cosmopolitan systemic infections with potential for transmission in the receiving communities. Implications for pre- and post-travel care of children are emphasized.

Brief Report: APOL1 Renal Risk Variants Are Associated With Chronic Kidney Disease in Children and Youth With Perinatal HIV Infection.

Abstract:APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case–control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2 to 10.0]. We report an unadjusted incidence of 1.2 CKD cases/100 person-years (95% CI: 0.5 to 2.5) in PHIV youth carrying APOL1 high-risk genotypes, with important implications for sub-Saharan Africa.

Genetically determined ancestry is more informative than self-reported race in Hiv-infected and -exposed children

AbstractThe Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants.In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined.According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian.GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes.

Adverse Pregnancy Outcomes Among Women Who Conceive on Antiretroviral Therapy

Background Adverse pregnancy outcomes for women who conceive on antiretroviral therapy (ART) may be increased, but data are conflicting. Methods Human immunodeficiency virus-infected, nonbreastfeeding women with pre-ART CD4 counts ≥400 cells/μL who started ART during pregnancy were randomized after delivery to continue ART (CTART) or discontinue ART (DCART). Women randomized to DCART were recommended to restart if a subsequent pregnancy occurred or for clinical indications. Using both intent-to-treat and as-treated approaches, we performed Fisher exact tests to compare subsequent pregnancy outcomes by randomized arm. Results Subsequent pregnancies occurred in 277 of 1652 (17%) women (CTART: 144/827; DCART: 133/825). A pregnancy outcome was recorded for 266 (96%) women with a median age of 27 years (interquartile range [IQR], 24-31 years) and median CD4+ T-cell count 638 cells/μL (IQR, 492-833 cells/μL). When spontaneous abortions and stillbirths were combined, there was a significant difference in events, with 33 of 140 (23.6%) in the CTART arm and 15 of 126 (11.9%) in the DCART arm (relative risk [RR], 2.0 [95% confidence interval {CI}, 1.1-3.5]; P = .02). In the as-treated analysis, the RR was reduced and no longer statistically significant (RR, 1.4 [95% CI, .8-2.4]). Conclusions Women randomized to continue ART who subsequently conceived were more likely to have spontaneous abortion or stillbirth, compared with women randomized to stop ART; however, the findings did not remain significant in the as-treated analysis. More data are needed on pregnancy outcomes among women conceiving on ART, particularly with newer regimens.

Sexually Transmitted Infections in Youth With Controlled and Uncontrolled Human Immunodeficiency Virus Infection

Background Sexually transmitted infections (STIs), including human immunodeficiency virus (HIV), disproportionately affect adolescents and young adults (AYAs) ages 13-24 years. Sexually transmitted infections likewise are a risk factor for HIV acquisition and transmission; however, there is a lack of data on STI acquisition in HIV-infected AYAs. Methods We determined the incidence of STIs in HIV-infected AYAs 12.5 <25 years of age in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1074 observational cohort study. Univariate and multivariable logistic regression models were used to evaluate the association of HIV control (mean viral load <500 copies/mL and CD4+ T cells >500 cells/mm3 in the year preceding STI diagnosis) and other risk factors with STI occurrence. Results Of 1201 enrolled subjects, 1042 participants met age criteria and were included (49% male, 61% black, 88% perinatally infected; mean age 18.3 years). One hundred twenty participants had at least 1 STI on study, of whom 93 had their first lifetime STI (incidence rate = 2.8/100 person-years). For individual STI categories, 155 incident category-specific events were reported; human papillomavirus (HPV) and chlamydial infections were the most common. In the multivariable model, having an STI was associated with older age (adjusted odds ratio [aOR] = 1.13; 95% confidence interval [CI], 1.05-1.22), female sex (aOR = 2.65; 95% CI, 1.67-4.21), nonperinatal HIV acquisition (aOR = 2.33; 95% CI, 1.29-4.22), and uncontrolled HIV infection (aOR = 2.05; 95% CI, 1.29-3.25). Conclusions Sexually transmitted infection acquisition in HIV-infected AYAs is associated with older age, female sex, nonperinatal HIV acquisition, and poorly controlled HIV infection. Substantial rates of STIs among HIV-infected AYAs support enhanced preventive interventions, including safe-sex practices and HPV vaccination, and antiretroviral adherence strategies.