Hospitalization and mortality rates significantly decreased among HIV-infected children receiving HAART. Most hospitalizations and deaths occurred during the first 24 weeks of HAART.

Background We investigated 18-month incidence and determinants of death and loss-to-follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. Methods HIV-infected children (positive PCR <18 months or positive serology ≥18 months) from IeDEA cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of two failure types: death and loss-to-follow-up (>6 months). Findings Data on 13611 children, from Asia (N=1454), East-Africa (N=3114), Southern-Africa (N=6212) and West-Africa (N=2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East-Africa, 5.4% in Asia, 5.7% in Southern-Africa and 7.4% in West-Africa (P=0.01). Age<24 months, WHO stage 4, CD4<10%, attending a private sector clinic, larger cohort size and living in West-Africa were independently associated with poorer survival. The adjusted risk of loss-to-follow-up was 4.1% in Asia, 9.0% in Southern-Africa, 14.0% in East-Africa, and 21.8% in West-Africa (P <0.01). Age<12 months, non NNRTI-based ART regimen, WHO stage 4 at ART start, ART initiation after 2005, attending a public sector or a non-urban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East or West-Africa were significantly associated with higher loss-to-follow-up. Conclusion Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV-services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at program level.

BACKGROUNDThe safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODSIn this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTSA total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], −4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, −0.39; 95% CI, −1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 personyears in the deferred group (rate difference, 0.01; 95% CI, −0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONSThe risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period.

Substitution of stavudine with zidovudine resulted in decreased severity or resolution of LD among HIV-infected children and adolescents.

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Human immunodeficiency virus (HIV)-negative children born to HIV-infected mothers may exhibit differences in neurodevelopment (ND) compared to age- and gender-matched controls whose lives have not been affected by HIV. This could occur due to exposure to HIV and antiretroviral agents in utero and perinatally, or differences in the environment in which they grow up. This study assessed neurodevelopmental outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children enrolled as controls in a multicenter ND study from Thailand and Cambodia. One hundred sixty HEU and 167 HUU children completed a neurodevelopmental assessment using the Beery Visual Motor Integration (VMI) test, Color Trails, Perdue Pegboard, and Child Behavior Checklist (CBCL). Thai children (n = 202) also completed the Wechsler Intelligence Scale (IQ) and Stanford-Binet II memory tests. In analyses adjusted for caregiver education, parent as caregiver, household income, age, and ethnicity, statistically significant lower scores were seen on verbal IQ (VIQ), full-scale IQ (FSIQ), and Binet Bead Memory among HEU compared to HUU. The mean (95% CI) differences were −6.13 (−10.3 to −1.96), p = 0.004; −4.57 (−8.80 to −0.35), p = 0.03; and −3.72 (−6.57 to −0.88), p = 0.01 for VIQ, FSIQ, and Binet Bead Memory, respectively. We observed no significant differences in performance IQ, other Binet memory domains, Color Trail, Perdue Pegboard, Beery VMI, or CBCL test scores. We conclude that HEU children evidence reductions in some neurodevelopmental outcomes compared to HUU; however, these differences are small and it remains unclear to what extent they have immediate and long-term clinical significance.

The World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty-seven women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting for NAT2 and CYP2B6 genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in CYP2B6 normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration were NAT2 and CYP2B6 genotypes, which resulted in a five-fold difference for both drugs between rapid and slow metabolizers.

Background Combination antiretroviral therapy (ART) has been used for HIV-infected children in many Asian countries since 2002. This study describes survival outcomes among HIV-infected children in a multicenter regional cohort in Asia. Patients and Methods Retrospective and prospective data collected through March 2009 from children in five countries enrolled in TREAT Asia's Pediatric HIV Observational Database (TApHOD) were analysed. Multivariate Cox proportional hazard models were used to assess factors associated with mortality in children who received ART. Results Among 2280 children, 1752 (77%) had received ART. During a median follow up of 3.1 years after ART, 115 (6.6%) deaths occurred, giving a crude mortality rate of 1.9 per 100 child-years (95% CI, 1.6-2.4). The mortality rate was highest in the first three months of ART (10.2 per 100 child-years; 95% CI, 7.5-13.7) and declined after 12 months (0.9 per 100 child-years; 95% CI, 0.7-1.3). Those with a low recent CD4 percentage, who started ART with lower baseline weight-for-age z-score, or with WHO clinical stage 4 had an increased risk of death. Of 528 (23%) children who never received ART, 36 (6.8%) died after presenting to care, giving a crude mortality rate of 4.1 per 100 child-years (95% CI 3.0-5.7), with a lost-to-program rate of 31.5 per 100 child-years (95% CI, 28.0-35.5). Conclusion The high mortality during the first three months of ART and in those with low CD4 percentage support the implementation of early diagnosis and ART initiation.