Long-term virological outcome in children receiving first-line antiretroviral therapy.

BACKGROUND: Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. METHODS: Perinatally HIV infected, ART-naive children, between 2 and 12 years of age, initiating NNRTI-based ART during 2010-2015, with at least 12 months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24 weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of > 1000 copies/ml at 48 weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. RESULTS: Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5-5.7) log10 copies/ml] were enrolled into the study. At 48 weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p < 0.001). The immunologic response was good; almost 90% of children showing an increase in their absolute CD4+ T cell count to more than 350 cells/mm3. Immunological failure was noted among 11% (28/261) and virologic failure in 29% (94/328) of children. Of the 94 children with virologic failure at 12 months, 36 children showed immunologic failure while the rest had good immunologic improvement. There was no demonstrable correlation between virologic and immunologic failure. 62% had reported > 90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%-K103N and Y181C being the major NNRTI mutations-observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2-12), specificity 97% (92.4-98.9), PPV 44% (13.7-78.8) and NPV was 72% (65-77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. CONCLUSIONS: Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.

Etiology and risk factors associated with a pruritic papular eruption in people living with HIV in India.

INTRODUCTION: Papulopruritic eruption (PPE) occurs in people living with HIV in India. Understanding the risk factors associated with this disease may help decrease the prevalence of PPE. METHODS: This study was a case-control study performed at the Government Hospital of Thoracic Medicine, a tertiary care hospital in Chennai, India. Cases included HIV-positive, antiretroviral (ARV) therapy-naïve adults experiencing a pruritic skin eruption for longer than one month, with evidence of multiple papular or nodular lesions and biopsy consistent with arthropod bite. Controls included HIV-positive, ARV-naïve patients without active skin rash. Main outcome measures were CD4 cell count, histology, and environmental exposures. We performed statistical analysis using Epi Info version 3.5.1 and SPSS version 11.0 (SPSS Inc., Chicago, IL). Categorical variables such as gender, urban versus rural residence, occupation, treatment history, CD4 count, use of insect repellents, and environmental exposures were evaluated using the χ(2) test (or the Fisher exact test when an expected value for a category was less than 5). The t-test was used to evaluate differences in age and the duration since HIV diagnosis. The Mann-Whitney test was used to compare non-normally distributed values such as CD4 cell count. A p-value that was less than 0.05 was considered to be statistically significant. RESULTS: Forty-one cases and 149 control subjects were included. Subjects with PPE had significantly lower CD4 cell counts compared to controls (225.5 cells/µL vs. 425 cells/µL; p=0.0001). Sixty-six percent of cases had a CD4 cell count less than 350 cells/µL. PPE cases were less likely to use mosquito repellent techniques (odds ratio 2.81, CI = 1.45-5.45). DISCUSSION: PPE may be an altered and exaggerated immune response to arthropod bites in HIV-positive patients. CD4 cell count is significantly lower in patients with PPE, and therefore it may be considered a qualifying clinical finding for ARV initiation in resource-poor settings. Protective measures against mosquito bites appeared to be important in preventing PPE in subjects at risk.

Randomized clinical trial of thrice-weekly 4-month moxifloxacin or gatifloxacin containing regimens in the treatment of new sputum positive pulmonary tuberculosis patients.

BACKGROUND: Shortening tuberculosis (TB) treatment duration is a research priority. This paper presents data from a prematurely terminated randomized clinical trial, of 4-month moxifloxacin or gatifloxacin regimens, in South India. METHODS: Newly diagnosed, sputum-positive HIV-negative pulmonary TB patients were randomly allocated to receive gatifloxacin or moxifloxacin, along with isoniazid and rifampicin for 4 months with pyrazinamide for first 2 months (G or M) or isoniazid and rifampicin for 6 months with ethambutol and pyrazinamide for first 2 months (C). All regimens were administered thrice-weekly. Clinical and bacteriological assessments were done monthly during treatment and for 24 months post-treatment. The Data and Safety Monitoring Board recommended termination of the trial due to high TB recurrence rates in the G and M regimens. RESULTS: Of 416 patients in intent-to-treat analysis, 6 (5%) of 124, 2 (2%) of 110 and 2 (2%) of 137 patients with drug-susceptible TB in the G, M and C arms respectively had unfavorable response at the end of treatment; during the next 24 months, 17 (15%) of 115, 11 (11%) of 104 and 8 (6%) of 132 patients respectively, had TB recurrence. Of 38 drug-resistant patients 1 of 8 and 3 of 26 in the G and C arms respectively had unfavourable response at the end of treatment; and TB recurrence occurred in 2 of 7 and 2 of 23 patients, respectively. The differences in TB recurrence rates between the G and C arms was statistically significant (p = 0.02). Gastro-intestinal symptoms occurred in 23%, 22% and 9% of patients in the G, M and C arms respectively, but most reactions were mild and manageable with symptomatic measures; 1% required regimen modification. CONCLUSIONS: 4-month thrice-weekly regimens of gatifloxacin or moxifloxacin with isoniazid, rifampicin and pyrazinamide, were inferior to standard 6-month treatment, in patients with newly diagnosed sputum positive pulmonary TB. TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2012/10/003060.