Phase IV, prospective, Randomized, Open Label Evaluation of The Efficacy of Once Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Individuals.
	Evaluation of a Diagnostic Algorithm for HIV positive Pulmonary TB suspects who are initially smear negative.
	Nevirapine versus Efavirenz-based highly active antiretroviral therapy regimens in antiretroviral-naive patients with HIV and Tuberculosis infection in India.
	HIV Drug Resistance Surveillance and Monitoring (Dr R S Paranjape, NARI) (funded by NACO / WHO)
	NeuroAIDS in India

1. Phase IV, prospective, Randomized, Open Label Evaluation of The Efficacy of Once Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Individuals.

Study Design:

A5175 is a phase IV, randomized, open-label, three-arm antiviral efficacy trial designed to evaluate three antiretroviral (ARV) regimens for treatment naïve HIV-infected participants one regimen containing two nucleoside reverse transcriptase inhibitors (NRTIs) + an HIV-1 protease inhibitor (PI) regimen, and two regimens each containing two NRTIs + a non-nucleoside reverse transcriptase inhibitor (NNRTI). This is a multi-centric international ART study with two centers in India (NARI at Pune and YRGCARE in Chennai).

The primary treatment comparisons in A5175 investigate:1) if a once-daily regimen containing two NRTIs + PI (Arm 1B) is not inferior to a twice-daily regimen containing two NRTIs + NNRTI (Arm 1A), and 2) if a once-daily regimen that contains two NRTIs + NNRTI (Arm 1C) is not inferior to a twice-daily regimen that also contains two NRTIs + NNRTI (Arm 1A). Both evaluations will be based on the primary study endpoint, time to treatment failure of the initial regimens (Step1).

Time to treatment failure will be defined as the time from randomization to the first occurrence of any of the following: 1) death due to any cause; 2) disease progression - defined as a new or recurrent AIDS-defining opportunistic infection or malignancy occurring after completion of 12 weeks of ARV treatment; 3) virologic failure defined as two successive measurements of plasma HIV-1 RNA =1000 copies/mL, with the first measurement at week 16 or later. Participants who experience virologic failure on the Step 1 initial regimen may receive a second ARV regimen in Step 2.

At entry participants will be randomized (1:1:1) to one of the following three treatment arms: Arm 1A: lamivudine (3TC)/zidovudine (ZDV) 150/300 mg PO BID + efavirenz (EFV) 600 mg PO QHS Arm 1B: emtricitabine (FTC) 200 mg PO QD + atazanavir (ATV) 400 mg PO QD + didanosine enteric-coated (ddI-EC) 400 mg PO QD for participants who weigh ³60 kg or 250 mg PO QD for participants who weigh < 60 kg  Arm 1C: Truvada [FTC 200 mg / tenofovir (TDF) 300 mg] PO QHS + EFV 600 mg PO QHS + EFV 600 mg PO QHS.

2. Evaluation of a Diagnostic Algorithm for HIV positive Pulmonary TB suspects who are initially smear negative.

Study Design:

This study is being carried out as a collaborative project between Tuberculosis Research Centre at Chennai and NARI in Pune. HIV seropositive subjects with history of cough for 2 weeks or more and have 3 negative sputum results for AFB are enrolled in the study. An additional 2 sputum samples are collected for sputum AFB and chest radiograph is also carried out. Subsequently, two weeks of antibiotics are administered following which three more sputum samples are collected for acid fast bacilli. If the sputum smears are all negative and the clinical evidence is not in favour of active TB, the subject is requested to come back after two months, when the results of sputum culture results are given to the patient.

So far, 150 subjects have been enrolled in the study and the target enrollment in the study at NARI is 270 subjects.

3. Nevirapine versus Efavirenz-based highly active antiretroviral therapy regimens in antiretroviral-naive patients with HIV and Tuberculosis infection in India.

This study is funded by NACO and is a collaborative project between All India Institute of Medical Sciences, New Delhi and the NARI in Pune.

Objectives of the study:

1. To compare clinical, virological and immunological responses to nevirapine (NVP)-based and efavirenz (EFV)-based highly active antiretroviral therapy (HAART) regimens in antiretroviral-naive patients with HIV and Tuberculosis infection on ATT.
2. To determine the safety of nevirapine based and efavirenz based highly active antiretroviral therapy regimens in antiretroviral-naive patients with HIV and Tuberculosis infection on ATT.
3. To study the response of switching back to nevirapine based regimen from efavirenz based regimen once ATT will over.
4. To characterize drug-associated toxicities of nevirapine based and efavirenz based regimens in HIV and Tuberculosis patients on ATT (especially hepatic, cardiac and hyperlipidemia).

Sample Size:

50 HIV infected TB patients would be randomized to the following two groups after obtaining informed consent:

• Group I - 75 patients with NVP-based highly active antiretroviral therapy regimen with anti-TB treatment.
• Group II - 75 patients with EFV-based highly active antiretroviral therapy regimen with anti-TB treatment.

So far, 32 subjects have been enrolled in the study and the study is ongoing at present.

4. HIV Drug Resistance Surveillance and Monitoring (Dr R S Paranjape, NARI) (funded by NACO / WHO)

The project to determine the Threshold Surveillance and for Monitoring the HIV Drug Resistance in the Mumbai and Chennai regions of India was initiated after obtaining the necessary Government approvals and the NARI and ICMR Ethics Committee approvals. Sample collection at the Mumbai and Chennai sites was initiated in August 2007 and at the Kakinada site in December 2007.

1. Survey to evaluate transmitted HIV drug resistance in recently infected, ARV-naive population attending: (a) voluntary counseling centres in Mumbai and (b) prevention of parent-to-child transmission (PPTCT) centre in Kakinada, East Godavari. Using binomial sequential sampling, blood specimens were collected from 70 eligible, consecutively selected individuals at each site, to assure amplification and genotyping of up to 47 specimens. In each geographical setting, for each drug and drug class used in the national ART regimens, the prevalence of HIV drug resistance will be categorized as < 5%, 5-15%, or >15%.

2. Survey to monitor the emergence of HIV drug resistance in population starting first-line ART attending (a) ART centre, JJ Hospital in Mumbai, and (b) ART centre, Tambaram Hospital in Chennai. At each site, a cohort of approximately 150 eligible patients starting first-line treatment was enrolled consecutively. Participants were evaluated at the start of ART (baseline) and followed-up at 12-15 months after start of treatment (or earlier if they stop, switch, are lost to follow-up or die).

Minimal demographic and clinical data as well as information on history of previous ARV or PPTCT was abstracted from clinic records. Baseline blood specimens was collected for genotyping.

At follow-up, drug adherence data is being obtained and blood specimens collected for viral load testing and genotyping. The proportion of individuals achieving viral suppression on first-line ART at 12 months will be calculated after the follow up at 12 months. Specific mutations and mutation patterns among participants not achieving viral suppression will be aggregated and described by specific mutation, mutation pattern, and for each drug and drug class.

National AIDS Control Organization Programme - NARI ART Link Centre

Total 264 patients were registered in the NACO ART NARI Centre by March 2008 out of which 72 were enrolled during April 2007- March 2008. Out of 72 participants during this year 41 were males and 31 were females. Five patients had side effects due to ART like lactic acidosis, AZT induced anemia, nausea, vomiting and acidity. Twelve were diagnosed with the opportunistic infections like Pulmonary tuberculosis, Oral candidiasis and Herpes zoster. There was increase in six monthly CD4 counts in these patients after initiation of ART.

5. NeuroAIDS in India

Principal Investigator:  Dr. Sanjay Mehendale MD, MPH

Co- Principal Investigator:  Dr. Manisha Ghate DCH MBBS

Funding Agency:  The study is being funded by the National Institutes of Mental Health

Budget for the study:   $ 2,511,110 for entire study period

Study period:  2008-2012

Sample size:  300 HIV infected at various CD4 counts and 300 HIV uninfected individuals

Study Period :                         2008 - 2010

A. Specific Aims

1. To determine the prevalence and nature of HIV associated neurocognitive impairment (HNCI) in individuals who are infected with clade C in India and untreated in a clinic-based setting.
2. To determine the impact of antiretroviral (ARV) treatment on HNCI.
3. To assess the viral genetics associated with HNCI in individuals infected with clade C HIV in India.
4. To determine the relationship between host factors and HNCI in individuals infected with clade C HIV in India.

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