Sanjay Ranjan

Outcomes of antiretroviral therapy in a northern Indian urban clinic

PROBLEM Antiretroviral therapy (ART) programmes have been successful in several countries. However, whether they would succeed as part of a national programme in a resource-constrained setting such as India is not clear. The outcomes and specific problems encountered in such a setting have not been adequately studied. APPROACH We assessed the efficacy and functioning of Indias national ART programme in a tertiary care centre in northern India. All ART-naive patients started on ART between May 2005 and October 2006 were included in the study and were followed until 31 April 2008. Periodic clinical and laboratory evaluations were carried out in accordance with national guidelines. Changes in CD4+ lymphocyte count, body weight and body mass index were assessed at follow-up, and the operational problems analysed. LOCAL SETTING The setting was a tertiary care centre in northern India with a mixed population of patients, mostly of low socioeconomic status. The centre is reasonably well resourced but faces constraints in health-care delivery, such as lack of adequate human resources and a high patient load. RELEVANT CHANGES The response to ART in the cohort studied was comparable to that reported from other countries. However, the programme had a high attrition rate, possibly due to patient-related factors and operational constraints. LESSONS LEARNT A high rate of attrition can affect the overall efficacy and functioning of an ART programme. Addressing the issues causing attrition might improve patient outcomes in India and in other resource-constrained countries.

Clinical characteristics of tuberculosis-associated immune reconstitution inflammatory syndrome in North Indian population of HIV/AIDS patients receiving HAART.

Background & Objective. IRIS is an important complication that occurs during management of HIV-TB coinfection and it poses difficulty in diagnosis. Previous studies have reported variable incidence of IRIS. The present study was undertaken to describe the pattern of TB-associated IRIS using recently proposed consensus case-definitions for TB-IRIS for its use in resource-limited settings. Methods. A prospective analysis of ART-naïve adults started on HAART from November, 2008 to May, 2010 was done in a tertiary care hospital in north India. A total 224 patients divided into two groups, one with HIV-TB and the other with HIV alone, were followedup for a minimum period of 3 months. The diagnosis of TB was categorised as ‘‘definitive” and ‘‘probable”. Results. Out of a total of 224 patients, 203 completed followup. Paradoxical TB-IRIS occurred in 5 of 123 (4%) HIV-TB patients while 6 of 80 (7.5%) HIV patients developed ART-associated TB. A reduction in plasma viral load was significantly (P = .016) associated with paradoxical TB-IRIS. No identifiable risk factors were associated with the development of ART-associated TB. Conclusion. The consensus case-definitions are useful tools in the diagnosis of TB-associated IRIS. High index of clinical suspicion is required for an early diagnosis.

Nevirapine versus efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and tuberculosis infections in India: a pilot study

BackgroundAdministration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings.MethodsA randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART.ResultsOf the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p = 0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group.ConclusionsOutcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection.Trial registrationNCT No. 01805258.

Efficacy and safety of thrice weekly DOTS in tuberculosis patients with and without HIV co-infection: an observational study

BackgroundDespite the latest World Health Organization guidelines advocating daily therapy in HIV-TB co-infected individuals, there are few recent studies comparing outcomes of thrice-weekly anti-tuberculosis treatment in HIV-positive and HIV-negative patients with TB. The present study sets out to compare TB treatment outcomes in these two groups in the Indian national programme, which currently involves thrice-weekly therapy for all, regardless of HIV status.MethodsHIV-positive and HIV-negative were consecutively screened for enrolment into this prospective observational study, carried out at the All India Institute of Medical Sciences hospital, New Delhi, India, between 2006 and 2010. Patients were given short-course thrice-weekly rifampicin-based therapy, with all HIV-positive patients being started on highly active antiretroviral therapy at least 14 days after commencing TB treatment. Patients were regularly followed-up for 24 months after completion of treatment.Results150 HIV-positive, 155 HIV-negative patients were enrolled consecutively for the study. Significantly higher treatment success (93.5% vs. 76.7% at end of treatment, p < 0.001) and lower mortality (2.8% vs. 21.6% on follow up, p < 0.001) were observed in HIV-negative patients. No significant difference was found in treatment failure (p = 0.16), sputum smear (p = 0.58) and culture conversion (p = 0.55), and non-serious adverse event incidence (p = 0.851) between the two groups. Low baseline CD4 cell count (<100 cells/ mm3) was the only predictor of mortality in HIV-TB patients (odds ratio 8 · 43, p = 0 · 013).ConclusionsThrice-weekly anti-tuberculosis therapy is more effective in HIV-negative than in HIV-positive patients. However, outcomes in this HIV co-infected cohort were found to be similar to those reported previously with daily therapy, with no safety concerns. This should prompt further study into whether intermittent or daily therapy should be used universally in resource-poor settings, using large well executed randomised controlled trials.Trial registrationNCT%20No.%2000698334

Malignancies in human immunodeficiency virus infected patients in India: Initial experience in the HAART era.

Background & objectives: Limited data are available on malignancies in human immunodeficiency virus (HIV)-infected patients from India. We undertook this study to assess the frequency and spectrum of malignancies in HIV-infected adult patients during the first eight years of highly active antiretroviral therapy (HAART) rollout under the National ART Programme at a tertiary care centre in New Delhi, India. Methods: Retrospective analysis of records of patients registered at the ART clinic between May 2005 and December 2013 was done. Results: The study included 2598 HIV-infected adult patients with 8315 person-years of follow up. Malignancies were diagnosed in 26 patients with a rate of 3.1 (IQR 2.1-4.5) cases per 1000 person-years. The median age for those diagnosed with malignancy was 45 (IQR 36-54) yr, which was significantly (P<0.01) higher compared with those not developing malignancies 35 (IQR 30-40) yr. The median baseline CD4+ T-cell count in patients with malignancy was 135 (IQR 68-269) cells/µl compared to 164 (IQR 86-243) cells/µl in those without malignancies. AIDS-defining cancers (ADCs) were seen in 19 (73%) patients, while non-AIDS-defining cancers (NADCs) were observed in seven (27%) patients. Malignancies diagnosed included non-Hodgkins lymphoma (16), carcinoma cervix (3), Hodgkins lymphoma (2), carcinoma lung (2), hepatocellular carcinoma (1), and urinary bladder carcinoma (1). One patient had primary central nervous system lymphoma. There was no case of Kaposis sarcoma. Interpretation & conclusions: Malignancies in HIV-infected adult patients were infrequent in patients attending the clinic. Majority of the patients presented with advanced immunosuppression and the ADCs, NHL in particular, were the commonest malignancies.

Once Daily Dose of Nevirapine (400 mg) Versus Twice-Daily Dose (200 mg) of Nevirapine-Based Highly Active Antiretroviral Therapy Regimens in Antiretroviral Naïve Patients with HIV and Tuberculosis Infection in India

Nevirapine-based antiretroviral therapy against human immunodeficiency virus (HIV) among Tuberculosis (TB) co-infected individual is complicated as administration of rifampicin along with Nevirapine reduces the plasma concentration of Nevirapine. The objective of the present study is to compare efficacy and safety of Nevirapine 400 mg once daily (OD) based antiretroviral therapy (ART) with efavirenz based ART and twice daily dose (200 mg) of Nevirapine-based ART regimens in HIV-TB co-infected individuals. ART-naive HIV-TB patients were randomly assigned to receive either Nevirapine 400 mg OD with zidovudine and lamivudine (Group 1; n=30), Nevirapine 200 mg BD (Group 2; n=30), efavirenz 600 mg (Group 3, n=31); Nevirapine 400 mg OD with tenofovir (Group 4; n=30) and Nevirapine 400 mg OD without concomitant antitubercular therapy (ATT) (Group 5; n=30). The end points were virological (viral load), immunological (CD4 count) and clinical responses and progression of HIV disease marked by the failure of ART. Our results suggest that Nevirapine 400 mg OD based therapy is as effective as efavirenz-based ART in terms of clinical, immunological and virological response. Our data suggests that Nevirapine 400 mg OD group had favorable treatment outcome as compared to Nevirapine 200 mg 1 BD group. We conclude that Nevirapine 400 mg OD based ART combined with tenofovir and lamivudine could be an effective alternative to improve compliance in the resource-limited settings in patients with HIV-TB co-infection. Further large multicentric study with bigger sample size will be required to confirm these findings.