Predictors of failure of first-line antiretroviral therapy in HIV-infected adults: Indian experience.

OBJECTIVES: To study the incidence and risk factors for failure of treatment with antiretroviral therapy among adults in the national treatment program in India, and to estimate the possible number of persons living with human immunodeficiency virus (HIV) who will need a second-line treatment regimen in the next 3 and 3.5 years. DESIGN AND SETTING: Data of a cohort of HIV-positive adult patients, who were enrolled in the government-sponsored antiretroviral therapy program, were obtained from the electronic medical record system of the largest HIV care center in India and subjected to analysis. MAIN OUTCOMES: Treatment failure defined by the World Health Organization criteria, assessed immunologically on the basis of CD4 T cell count, with a minimum period of 12 months of follow-up and with a minimum of two CD4 T cell follow-up measures. RESULTS: The cumulative incidence of treatment failure in the 1370 adult patients included in the study was 3.9% (95% confidence interval [CI] 2.9 to 4.9). Men had a 3.5 (1.6 to 7.4) times significantly greater risk of treatment failure. Patients who had negative changes in absolute lymphocyte count, hemoglobin concentration and body weight had 3.1 (1.6 to 6.2), 3.2 (1.6 to 6.2), and 3.5 (1.9 to 6.4) times significantly greater risk of treatment failure. In India, after 2007, by 2, 3, and 3.5 years, respectively, an estimated 16 000, 35 000, and 51 000 patients receiving antiretroviral therapy are likely to require second-line treatment. CONCLUSION: Monitoring of hemoglobin concentration, absolute lymphocyte count, and body weight during follow-up emerged as inexpensive predictors of treatment failure in a resource-poor setting. A significant number of patients will need second-line therapy as a result of failure of their first-line antiretroviral therapy regimen in 3 and 3.5 years in India, and therefore the development of an appropriate policy for second-line drugs is urgently needed.

Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in HIV patients with culture confirmed pulmonary tuberculosis in India and the potential role of IL-6 in prediction.

BACKGROUND: The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. METHODS: HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. RESULTS: Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14-47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7-16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9-23). Two patients died due to CNS TB-IRIS. Lower CD4(+) T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. CONCLUSION: Paradoxical TB-IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions.

Increasing nevirapine dose can overcome reduced bioavailability due to rifampicin coadministration.

We studied the effect of rifampicin on steady-state pharmacokinetics of nevirapine and the impact of increasing the dose of nevirapine on its peak (Cmax) and trough (Cmin) levels in 13 HIV-infected patients on regular antiretroviral treatment with nevirapine-containing regimens (200 mg twice daily). A baseline pharmacokinetic study was conducted and repeated after 1 week of daily rifampicin (450/600 mg). The study was repeated in 7 of 8 patients who had subtherapeutic Cmin nevirapine levels after increasing nevirapine dose to 300 mg twice daily. Liver function was monitored. Rifampicin caused significant reductions in Cmax (42%), Cmin (53%), and exposure (46%) of nevirapine (P <.01). The Cmin of nevirapine fell below the therapeutic range of 3 microg/ml in 8 of 13 patients. An increase of nevirapine to 300 mg twice daily raised Cmin to therapeutic range in all 7 patients without exceeding the toxic level of 12 microg/mL. There were no clinical or laboratory adverse events. Our findings suggest that decreased bioavailability of nevirapine because of rifampicin coadministration could be overcome by increasing the dose of nevirapine from 200 to 300 mg twice daily without short-term adverse events. Further studies to evaluate the long-term safety of higher dose of nevirapine are required.