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ONGOING PROJECT
1. Clinical Trials Unit at National AIDS Research Institute, Pune, India: (NARI CTU)
Brief description of the study:
This study provides support to building clinical, laboratory, data management and community work infrastructure to carry our Phase I, II and III clinical trials with evaluable biological end-points in the areas of HIV prevention and therapeutic research. The clinical trials will be conducted by the Clinical Trials Unit [CTU] located at NARI through the following Clinical Research Sites in Pune city.
NARI CRS at National AIDS Research Institute NIV CRS at National Institute of Virology Gadikhana CRS at Dr. Kotnis Municipal Dispensary, Pune Womens' study clinic, Ganesh Peth, Pune [Being established] Womens' study clinic, Ganesh Peth, Pune [Being established]- HIV Prevention Trials Network sponsored HPTN 052 study in HIV discordant couples
- AIDS Clinical Trials Group sponsored ACTG 5175 and 5190 studies
- Microbicides Trials Network sponsored MTN 005 study of intra-vaginal ring [Proposed]
Brief description of the study:
Multicentric, Randomized (1:1), Open Label The study is being conducted in different parts of the world and the expected sample size for Pune is HIV discordant 242 couples.
Principal Investigator: Dr. Sanjay Mehendale MD, MPH
Investigator of Record: Dr. Sheela V. Godbole MD
Category:HIV Prevention Research, Randomized Controlled Clinical Trial
Collaborators:Family Health International and Johns Hopkins University, USA.
Funding Agency:The study is being funded by the National Institutes of Health of the US government through HIV Prevention trials Network and Family Health International; funded by the Division of AIDS.
Budget for the study: $ 12,00,852 [Study specific protocol implementation funds [PIF] for Year II (Feb 08 – Jan 09)]
Objectives:
To determine the long-term safety of two ART Regimen strategies (immediate versus delayed ART) for the treatment of HIV-1 infection. To characterize and compare the patterns and rates of antiretroviral drug resistance of two antiretroviral treatment strategies. To assess factors associated with adherence and to compare the adherence rate of two antiretroviral treatment strategies. To evaluate the usefulness of measures of virologic and immunologic efficacy and measures to detect antiretroviral drug resistance. To determine, characterize and compare the rates of AIDS-defining illness, sexually transmitted diseases, opportunistic infections and immune reconstitution syndromes, with regard o outcomes and survival as observed in different geographic settings andby treatment strategies. To determine and characterize the rates of antiretroviral drug-associated toxicities observed in different geographic settings and by treatment strategies. To evaluate the effectiveness of couples HIV counseling and characterize the patterns of sexual behaviour in couples in both arms of the study.Study rationale, procedures and status:
Sexual Transmission of HIV is the commonest mode of transmission especially in India. Plasma HIV-1 RNA levels can be correlated with the sexual transmission of HIV (Trial done in Uganda, Zambia). ART decreases the concentration of HIV-1 RNA not only in blood but also in male and female genital secretions, rectal mucosa, and saliva, thereby reducing the levels of HIV innoculum to which the susceptible partner is exposed. Hence reducing Plasma HIV-1 levels may decrease transmission of HIV-1.
Thus, this study will assess the use of Anti Retroviral Therapy for Prevention of HIV Transmission in HIV discordant couples [one partner is HIV seropositive (INDEX) and the other is HIV seronegative (PARTNER)]. The study will also try to provide evidence on when is the better time to initiate antiretroviral therapy in HIV-1 infected persons: early or later. About 1750 HIV Discordant Couples in whom the infected partner has a CD4 cell count between 350-550 cells/mm3 will be enrolled in total 9 sites across the world [about 250 couples per site]. The Participants would be randomized to two Arms in this study: Arm 1: Immediate ART + Primary Care and Arm 2: Delayed ART + Primary HIV Care with initiation of ART when 2 consecutive CD4 counts are < 250 per cumm or AIDS defining illness occurs.
The study is currently enrolling HIV discordant couples and it is expected that by 2008 end, enrollment at Pune site will be completed.
An Abstract has been accepted at the XVII International AIDS Conference Mexico City, 3-8 August 2008 for poster presentation: ‘Antiretroviral therapy to prevent the sexual transmission of HIV-1: Initial results from HPTN 052’. Sheela Godbole1, Nagalingeswaran Kumarasamy2, Ying Chen3, et al.
Implementing ICMR institutes:
National AIDS Research Institute (NARI), Pune National Institute of Epidemiology (NIE), Chennai National Institute of Nutrition (NIN), Hyderabad Regional Medical Research Center (RMRC), Dibrugarh National Institute of Medical Statistics (NIMS) Delhi Karnataka Health Promotion Trust (KHPT), BangaloreTechnical Assistance: Family Health International (FHI)
Funded by: Bill and Melinda Gates Foundation (BMGF)
Background:
HIV/AIDS in India is a still concentrated amongst certain high-risk populations such as Female Sex Workers (FSW), Men who have Sex with Men (MSM) and Injecting Drug Users (IDU). With the aim of slowing down the HIV epidemic in India, in the year 2003 Bill & Melinda Gates Foundation (BMGF) initiated Avahan program focusing these high-risk groups in high prevalence states through HIV prevention service providers and offering service packages in line with National AIDS Control Program (NACP). The Integrated Behavioral and Biological Assessment (IBBA) is the first independent evaluation of the Avahan intervention among these populations.
In the first round of IBBA, 29 districts from six states, viz., Andhra Pradesh, Karnataka, Maharashtra, Tamil Nadu, Manipur and Nagaland were covered. Field work was carried out by reputed research agencies.
| IBBA (Round-1) Coverage | |||
| States | Districts | Survey Groups | Sample Achieved |
| Andhra Pradesh | 8 | 17 | 6912 |
| Karnataka | 6 | 2560 | |
| Maharashtra | 6 | 9 | 6230 |
| Tamil Nadu | 5 | 13 | 5260 |
| Nagaland | 3 | 3 | 1286 |
| Manipur | 2 | 2 | 839 |
| National Highway | 4(NH routes) | 4 | 2075 |
| Total | 25162 | ||
Objectives:
To measure the major outcomes and impacts of the interventions funded by ‘Avahan’ under the “India AIDS Initiative”;
To make available data that will be used for estimating sizes of populations targeted by the Avahan project; and To make information available to a partner organization under Avahan for modeling the impact of the intervention. To measure the major outcomes and impacts of the interventions funded by ‘Avahan’ under the “India AIDS Initiative”;IBBA procedures:
The IBBA in the selected districts was initiated with mapping of the sub populations and it was followed by sampling frame development. Simultaneously Community Advisory Boards (CAB) and Community Monitoring Boards (CMB) were established as a part of harm minimization protocol for protecting participants’ rights.
Survey details:
First IBBA survey was piloted in Karimnagar, Andhra Pardesh in October 2005. followed by the surveys among IDUs, MSM, Clients of FSWs and FSWs, across the six prevalent states mentioned above and the long distance truck drivers, helpers along the four National Highways. The average time spent in completing one survey group was 6 -8 weeks. The first round was completed in November 2007 with completion of Bar Girl Survey in Mumbai.
Uniqueness of IBBA:
25,162 sample size spread over Six states, twenty nine districts, four highway sites, (Total 64 Surveys), 180 behavioural and seven biological variables for each participant makes this study unique.
Highlights of data:
FSWs:
The majority of FSW were illiterate in all districts. Consistent condom use with clients was generally high, but lower with regular commercial clients compared with occasional clients. Coverage of interventions by any agency was relative low in bigger cities (Chennai, Mumbai and Hyderabad) compared to other districts Syphilis was the predominant STI in most of the districts. HIV prevalence was also high in many districts, with Maharashtra having the highest prevalence rates. Among the IBBA districts in Tamil Nadu, Chennai had the lowest HIV prevalence.MSM:
Most of the MSM were literate across all districts. Exposure to various intervention services provided by any agency was moderate. MSM reported low levels of condom use for anal sex with their regular sexual partner in all districts except Bangalore. Condom use (last time) with paying male partners was high (above 70%) in all districts. HIV prevalence was above 20% in two districts of Andhra Pradesh (East Godavari and Hyderabad) and in Madurai district of Tamil Nadu.IDUs:
Exposure of IDUs to the various intervention programs was around 50% in the districts surveyed. (Mumbai in Maharashtra, Bishnupur, Churachandpur in Manipur and Wokha and Phek in Nagaland) A majority of the IDUs reported that their usual place of injecting was in their own home or at the home of their injecting partner. Heroin was the most commonly injected drug among almost all IDUs. Only a very small proportion of IDUs reported having commercial sex partners in the past one year and condom use was relatively low. The STI prevalence was low in Manipur; however, the HIV prevalence was high.Clients of FSW:
Many of the clients reported low consistent condom use with sex workers. HIV prevalence above 5% was observed among clients of sex workers in Andhra Pradesh and Maharashtra. In all the above districts, except Vizag, the prevalence of syphilis was also high.
4. HIV-Cervical Cancer Prevention Research Program
Brief description of the study:
Prospective, observational, cohort study. The study is part of a network of four sites in India with the Pune site undertaking prospective follow-up of 300 HIV-infected women.
Principal Investigator: Dr. Sanjay Mehendale MD, MPH
Category: HIV Secondary Prevention Research / Epidemiological study.
Collaborators:
Funding Agency:
The study is being jointly funded by the National Institutes of Health of the US government (through National Cancer Institute, Fogarty International Center and Vanderbilt University) and Indian Council of Medical Research.
Budget for the study: Rs. 26,000,000 (from ICMR) and $99,000 (from NIH)
Objectives:
To expand the research capacity at our existing site (‘VIA clinic’ run by NARI-Vanderbilt University-B.J. Medical College) follow-up of the 300 HIV-infected women enrolled in our current NIH-funded study; with the following specific aims: Determining the incidence of colposcopic-histologically confirmed high-grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) in HIV-infected women prospectively followed in the study. Calculating the sensitivity and specificity of cervical cytology, VIA and HPV testing compared against the colposcopic-histologic ‘gold standard’ among HIV-infected women followed in the study. Describing the change of cervical HPV type compositionover time among HIV-infected women enrolled and followed-up over the year in the study. To develop research capacity through development of clinical research infrastructure and community involvement plan for recruitment and retention of HIV-infected study participants at three new sites in India: The proposed site expansion will be to achieve the following specific aims:
5. Annual HIV Sentinel Surveillance [HSS] for HIV infection
Brief description of the study:
National AIDS Control Organization (NACO) conducts Annual HIV Sentinel Surveillance all over India with the help of National Institute of Health and Family Welfare and National Institute of Medical Statistics since 1998. With a view to improve the quality of the programme, five Regional Institutes were identified and mandated to train, advice, guide, monitor and evaluate HSS in their assigned states. National AIDS Research Institute (NARI) was identified as the Regional Institute for western India.
Regional Institute Coordinator: Dr. Sanjay Mehendale MD, MPH
Other NARI Core team members: Dr. A.R. Risbud and Dr. S.V. Godbole
Category: Operations Research
Funding Agency: National AIDS Control Organization.
Budget for the study: Rs. 26 lakh per year
Period:Ongoing annual activity since 2006
Objectives:
To perform as Regional Institute and to undertake following activities in western states of India namely -
Maharashtra & Mumbai Madhya Pradesh Rajasthan Gujarat Goa Daman & Diu Dadra & Nagar HaveliActivities:
In all the assigned states NARI is responsible to conduct the following activities
Selection of new sites Selection of new testing laboratories Quality control measures Finalization of Timelines Training Monitoring surveillance Overall supervision of the survey Data analysis Provide suggestions for improvement in future rounds Conduct pre surveillance and post surveillance meetings of state level AIDS Control Societies
Principal Investigator: Dr. Sanjay Mehendale, Deputy Director [SG]
Funding Agency:Family Health International
Budget: Total study budget US $ 116790
Type of Research: A basic social science research with focus on prevention.
Period:2006-08
Introduction: This was a behavioral study running parallel to Phase II Clinical Trial of Tenofovir Gel, HPTNO59 Study.
Research Objectives:
Develop women’s, men’s and couple-based measures for psychometric variables related to HIV risk perception, sexual self-efficacy, couple harmony and product acceptability on which women and their partners score differently. Identify those individual and couple-based factors that best predict consistent use of microbicides. Factors to be examined relate to HIV risk perception, sexual self-efficacy, couple harmony, attitudes towards product attributes, and aspects of the clinical trial (including motivation to comply and the influence of trial- related counseling and services). Examine the reciprocal influence of different levels of microbicide use on the above individual and couple-based psychosocial factors. Identify factors that predict the likelihood of choosing to use a microbicide once participation in the research study has ended.Study procedures and current status:
The study involved collection of both qualitative and the quantitative data from the women participating in the HPTN059 study (CT cohort) and the women not eligible or not participating in the 059 study (NON CT Cohort). The qualitative data included collection of information from the participants on a psychosocial scale. The scale had questions on three subscales viz: pervasive HIV risk scale, couple harmony scale, protection control scale. In addition information on the general interest in gel use outside research scale and the motivation to comply with the clinical trial subscale was collected from the women enrolled in the clinical trial cohort. Partners of the women in both the cohorts were also enrolled in the third male cohort. Data was collected from 100 women in each cohort and at least 50% of their partners. The quantitative data was collection at baseline and at every two months interval for six months.
The qualitative information using in depth interviews was collected from a subset of participant i.e. 10 from each cohort. Information was also collected from atleast 50% of the partners of the women from both the cohorts. The constructs for enquiry in the interview guide included information on the family characteristics , household decision making, decision on trial participation , marital harmony, sexual and reproductive decision making, effect of participation in the trial on the daily life, knowledge and susceptibility of HIV/AIDS, risk reduction behavior, knowledge about the microbicides trial and the acceptability of microbicides in general. The qualitative information was collected in the 3rd and the 5th month of follow up. In depth interviews of the care providers involved in the 059 trial was also undertaken with the view to know their attitudes about microbicides acceptability and to see its effect on the retention of the trail participants.
The study was started in the month of July 2006 and started enrolling participants in September 2006. The study has completed all the follow ups with 100% retention in both the cohort and the male participants.
At present the data is being cleaned and would be analyzed and the findings will be presented to the participants and the researchers in a dissemination meeting.
7. ADVAX [DNA] and TBC-M4 [MVA] Prime Boost HIV-1 subtype C vaccine trial
Category: HIV Prevention Research, Phase I human clinical trial using two vaccine candidates
Principal Investigator: Dr Sanjay Mehendale
Co-Investigators: Dr Seema Sahay, Dr Madhuri Thakar
Protocol Title: A Phase I Double-Blind, Placebo-Controlled, Randomized Trial to Evaluate the Safety and Immunogenicity of TBC-M4, a multigenic MVA HIV Vaccine vs ADVAX, a multigenic DNA HIV Vaccine followed by TBC-M4, a multigenic MVA HIV Vaccine
Sponsors: International AIDS Vaccine Initiative , NY, USA.
Study sites: National AIDS Research Institute, Pune and Tuberculosis Research Centre, Chennai
Study Period : 2008 - 2010
Objectives :
Primary : To evaluate the safety of intramuscularly administered ADVAX DNA HIV vaccine at time 0 and 1 month, followed by TBC-M4 at months 3 and 6, compared with TBC-M4 administered intramuscularly at 0, 1, and 6 months. Secondary : To evaluate the immunogenecity of intramuscularly administered ADVAX DNA HIV vaccine at time 0 and 1 month, followed by TBC-M4 at months 3 and 6, compared with TBC-M4 administered intramuscularly at 0, 1, and 6 months. Other : To examine the safety & immunogenicity of the construct in the presence of pre-existing immunity against vaccinia, if any participants have such immunity.Study design : Randomized, double blind, placebo controlled , Prime Boost trial using ADVAX, a DNA vaccine and TBC- M4, a MVA vaccine
Study procedures:
Around 16 healthy, HIV uninfected men and women who are at low risk of acquiring HIV will be screened to determine eligibility to participate.
Eligibility Asessment: Sixteen healthy volunteers at low risk of HIV infection will be enrolled in this trial. The eligibility of interested volunteers will be assessed during screening procedure.
Enrollment in trial:
The eligible persons willing to participate in the study will be randomized in two groups,
- One group of eight volunteers will receive homologous prime boost regimen comprising of MVA based vaccine TBC-M4
- The second group of eight volunteers will receive heterologous prime boost regimen comprised of DNA vaccine - Advax and MVA based vaccine TBC-M4
Participants assigned to Group A will receive first ADVAX vaccine /placebo injection at enrollment and second after 1 month. At 3 and 6 months, they will receive TBC-M4 vaccine / placebo injections.
Participants from Group B will receive injection TBC-M4 vaccine/placebo at enrollment, and at 1 and 6 months following enrollment.
The participants will be followed for 12 months after the last study injection. During the follow up period, safety and immunogenicity assessments will be carried out.
Total duration of study participation for each volunteer will be 18 months.
Status: This trial has been approved by all relevant regulatory bodies. Screening/Enrollment is ongoing
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