Implementation and Operational Research: Implementation of the WHO 2011 Recommendations for Isoniazid Preventive Therapy (IPT) in Children Living With HIV/AIDS: A Ugandan Experience.

BACKGROUND: Intensified tuberculosis (TB) case finding and isoniazid preventive therapy (IPT) are strongly recommended for children who are HIV infected. Data are needed to assess the feasibility of the WHO 2011 intensified tuberculosis case finding/IPT clinical algorithm. METHODS: Children who are HIV infected and attending Nsambya Home Care at Nsambya Hospital, Uganda, were screened for TB following WHO recommendations. IPT was given for 6 months after excluding TB. Factors associated with time to IPT initiation were investigated by multivariate Cox proportional hazard regression. Health care workers were interviewed on reasons for delay in IPT initiation. RESULTS: Among the 899 (49% male) children with HIV, 529 (58.8%) were screened for TB from January 2011 to February 2013. Children with active TB were 36/529 (6.8%), 24 (4.5%) were lost to follow-ups and 280 (52.9%) started IPT, 86/280 (30.7%) within 3 months of TB screening and 194/280 (69.3%) thereafter. Among the 529 children screened for TB, longer time to IPT initiation was independently associated with cough at TB screening (hazard ratio 0.62, P = 0.02, 95% confidence interval: 0.41 to 0.94). Four children (1% of those starting treatments) interrupted IPT because of a 5-fold increase in liver function measurements. In the survey, Health care workers reported poor adherence to antiretroviral therapy, poor attendance to periodic HIV follow-ups, and pill burden as the 3 main reasons to delay IPT. CONCLUSION: In resource-constrained settings, considerable delays in IPT initiation may occur, particularly in children with HIV who are presenting with cough at TB screening. The good safety profile of isoniazid in antiretroviral-therapy-experienced children provides further support to IPT implementation in this population.

Predictors of Treatment Failure in HIV-Positive Children Receiving Combination Antiretroviral Therapy: Cohort Data From Mozambique and Uganda.

BACKGROUND: Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)-infected children of low-middle-income countries (LMIC). METHODS: An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models. RESULTS: Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26-33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5-22.9). Having tuberculosis co-infection or WHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4-17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudine-efavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution. CONCLUSIONS: Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.

Viral load detection using dried blood spots in a cohort of HIV-1-infected children in Uganda: correlations with clinical and immunological criteria for treatment failure.

Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children in Uganda. Of 104 children on combined antiretroviral treatment (cART), 12.5% experienced clinical and/or immunological failure, while 28.8%, 44.2%, and 26.9% had VLs of <1,000, 1,000 to 5,000, and >5,000 copies/ml, respectively. Clinical/immunological failure poorly predicted virological failure.

Epstein-Barr virus load in children infected with human immunodeficiency virus type 1 in Uganda.

BACKGROUND: Epstein-Barr Virus (EBV) is involved in a wide range of malignancies, particularly in immunocompromised subjects. In Africa, EBV primary infection occurs during early childhood, but little is known about the EBV load in Human Immunodeficiency Virus type 1 (HIV-1)-infected children. METHODS: Blood samples from 213 HIV-1-infected children, 140 of whom were receiving antiretroviral therapy (ART), were collected at the Nsambya Hospital in Kampala, Uganda, and obtained for dried blood spot analysis. Nucleic acids were extracted and analyzed for quantification of EBV types 1 and 2; 16S ribosomal DNA (rDNA), a marker of microbial translocation; and HIV-1 RNA. RESULTS: Ninety-two of 140 children (66%) receiving ART and 57 of 73 ART-naive children (78%) had detectable EBV DNA levels. Coinfection with both EBV types was less frequent in ART-treated children than in ART-naive children (odds ratio, 0.54 [95% confidence interval {CI}, .30-.98]; P = .042). Mean EBV DNA levels (±standard deviation) were lower in the former (3.99 ± 0.59 vs 4.22 ± 0.54 log10 copies/mL; P = .006) and tended to be inversely associated with ART duration. EBV DNA levels were higher in children with an HIV-1 RNA load of > 3 log10 copies/mL of blood (regression coefficient, 0.32 [95% CI, .05-.59]; P = .020) and correlated with circulating 16S rDNA levels (rs = 0.25 [95% CI, .02-.46]; P = .031). CONCLUSIONS: These findings suggest that ART, by limiting HIV-1 replication, microbial translocation, and related immune activation, prevents superinfection with both EBV types and keeps EBV viremia down, thus potentially reducing the risk of EBV-associated lymphomas.