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COMPLETED PROJECT
This first Phase-I trial of a newly developed experimental AIDS vaccine was conducted at 2 sites in Germany and Belgium and at NARI in Pune, India. The study was sponsored by the International AIDS Vaccine Initiative (IAVI). The experimental vaccine that was used in the trial was called tgAAC09.
Objectives:
To evaluate the safety of the vaccine and its ability to generate immune response in 30 HIV-uninfected, healthy Indian.
| GROUP | NUMBER OF VOLUNTEERS | DOSE |
|---|---|---|
| Vaccine/Placebo | ||
| Low Dose | 8/2 | 3 x 109 DRP or placebo |
| Mid Dose | 8/2 | 3 x 1010 DRP or placebo |
| High Dose | 8/2 | 3 x 1011 DRP or placebo |
Volunteers:
The community sensitization effort was initiated in December 2004. A three level recruitment plan was devised for recruitment of healthy volunteers. A two step informed consent for screening and enrollment and a consent comprehension test ensured the informed decision made by the volunteer for actual enrollment. In all 80 persons, 31 men and 49 women participated in the screening evaluation of which 30 (16 men and 14 women) were enrolled in the clinical trial. The enrolled participants were between age 20 to 49 years with mean age of 34 years.100% retention was achievedthrough specific counseling to each volunteer at every visit.
Safety and immunogenicity assessments were carried out at designated time points as per the schedule of procedures. The vaccine appears to be safe and well-tolerated at all dosage groups. No vaccine-related serious adverse events were reported. Three adverse events were judged to have possible relationship with administration of vaccine. Cellular immunogenicity was assessed using a IFN-? secretory ELISPOT assay, designed to detect the number of T-cells releasing IFN- ? from stimulated PBMCs. Overall 5 of 25 (20%) of volunteers from highest dose tested
(3x1011 DRP), responded by ELISPOT. Response rates after receipt of placebo, 3x109 DRP and 3x1010 DRP were 1 of 16 (6%), 1 of 16 (6%) and 2 of 23 (9%), respectively. All responses were to gag epitopes and the magnitude was modest (40-385 SFC/106 PMBC). No anti-gag antibodies were detected in the serum samples of any of the volunteers participated in the vaccine trial. A dose-dependent increase in geometric mean anti-AAV2 neutralizing titres was observed after vaccination with tgAAC09. The percentage of responders at each dose level was similar in Indian and European volunteers, even though more Indian volunteers (97%) had detectable baseline titres than European volunteers (48%).
The paper presenting the findings of this study has been accepted for publication in AIDS Researchand Human Retroviruses: A Phase 1 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV-1 Subtype C Adeno-Associated Virus Vaccine. S Mehendale, van Lunzed Jan, Clumeck Nathan et al.
2.HIV Incidence and Participant Retention Protocol [HPTN 034 Study]
HIV Incidence and Participant Retention Protocol [HPTN 034] was a prospective cohort study of HIV incidence conducted in Pune, India. The overall objective of this study was to provide an opportunity for the HIV Prevention Trial Unit in Pune to prepare for upcoming microbicides and clinical trials. Therefore, HPTN 034 enrolled two cohorts. The first cohort consisted of HIV-negative, non-sexworker, adult women who are attending STD clinics in Pune (these women meet general enrollment criteria for the planned microbicides trials), and the second cohort consisted of HIV sero-discordant sexual couples (the index cases meet general enrollment criteria for the ongoing antiretroviral trials). The study was initiated during September 2002 and was closed on August 31, 2005.
Specific objectives:
To determine the current incidence of HIV among a cohort of 400 newly identified high risk women as well as among 400 HIV-uninfected partners of HIV-infected persons. To determine the retention rate in high-risk women, as well as HIV-serodiscordant couples, among a target population eligible for screening for upcoming HPTN clinical trials. To assess risk factors for HIV and other STDs in high-risk women and among HIV-serodiscordant couples. To identify and address potential barriers to participation and high-level retention (>95% 1-year retention) for the upcoming clinical trials.
Enrollment and retention:
The study was designed to enroll HIV negative high-risk women and HIV serodiscordant couples and subsequent follow-up once every 3 months for one year. Enrollment to the study in both the cohorts was completed by November 2004. In all, 1014 HIV-serodiscordant couples were screened and of them, 457 couples were enrolled in the 27-month enrollment period. The corresponding figures for the HIV negative high-risk women cohort were 1015 and 423 women, respectively.
All study participants are expected to complete one year of follow-up, with study visits at three, six, nine, and twelve months. At study close-out (as of 31 August 2005), the 3-month, 6-month, 9-month, and 12-month retention rates for the HIV sero-discordant couples cohort were 95%, 92%, 88%, and 90%, respectively. The retention rates in the HIV negative high-risk women’s cohort were 75%, 66%, 61%, and 64%, respectively.
Incidence estimates:
In the couple’s cohort, seven uninfected partners sero-converted in 491 person-years of follow-up. Overall incidence estimate was 1.43 per 100 person-years (95% CI 0.57-2.94%). In the women’s cohort, one woman seroconverted resulting in an overall incidence estimate of 0.38 per 100 person-years (95% CI 0.01 to 2.13%).
Major achievements:
First estimates of HIV-1 incidence among married serodiscordant couples in Pune, India
First estimates of rate and cost of hospitalization in HIV infected individuals in Pune, India
First estimates of common opportunistic
infections in a propective cohort of HIV infected individuals in Pune, India
Study of reported sexual practices among partners of discordant couples and agreement of reporting between both the partners
Publications:
Rate of hospitalization and inpatient care costs for HIV-1-infected patients in Pune, India. Natl Med J India. 2006 Jan-Feb;19(1):10-4. Ghate MV, Tripathy SP, Kumar BK, Godbole SV, Chittake A, Nyayanirgune P, Gangakhedkar RR, Divekar AD, Thakar MR, Risbud AR, Bollinger RC, Mehendale SM.
Low HIV-1 incidence among married serodiscordant couples in Pune, India.J Acquir Immune Defic Syndr. 2006 Mar;41(3):371-3. Mehendale SM, Ghate MV, Kishore Kumar B, Sahay S, Gamble TR, Godbole SV, Thakar MR, Kulkarni SS, Gupta A, Gangakhedkar RR, Divekar AD, Risbud AR, Paranjape RS,Bollinger RC..
Incidence of common opportunistic infections in HIV infected individuals in Pune, India: Analysis by stages of immuno-suppression represented by CD4 counts. Manisha V Ghate,Swapna S Deshpande, M.Sc; Srikanth P Tripathy , Madhura Nene, Preeti Gedam , Sheela V Godbole, Madhuri R Thakar, Arun R Risbud, Robert Bollinger, Sanjay M Mehendale. Accepted for publication in International Journal of Infectious Diseases.
HPTN 059 study was a multi-centric Phase II study of 1% Tenofovir Gel vaginal microbicide. The study was sponsored by National Institutes of Health, USA under the HIV Prevention Trials Network. Apart from NARI, Pune other international sites are in Bronx Lebanon Hospital Center and University of Alabama in the United States. The total sample size of this study is 200 with 100 enrollments at NARI and 100 in the US. The goal of this study is to determine the safety of tenofovir 1% gel as a vaginal microbicide over 24 weeks of use, and to gain additional information about the product's acceptability. The study was a four-arm, randomized, double-blind, controlled trial, comparing two frequencies of study gel use (daily and coitally dependent) and corresponding study arms in which participants used a placebo gel.
The study was initiated in August 2006 at NARI and enrollment of 100 participants was completed in March 2007. The study has been completed with 100% retention at NARI and >95% retention at the international sites. The overall safety profile of the product was good at all the three participating sites. The data are being analyzedand manuscripts on safety and acceptability are being finalized.
4. Previously completed vaginal microbicide studies
a. Phase II study to assess safety, acceptability and adherence of a candidate microbicide 1% tenofovir gel
This was a four-arm, multi-center, randomized controlled Phase II (expanded safety) trial that aims to assess the safety and acceptability of an antiretroviral-based candidate microbicide called tenofovir topical gel (1 % tenofovir gel) used either daily or before each act of sex. This study was sponsored by Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), NIH and conducted by National AIDS Research Institute under Microbicide trial Network (HIV prevention trial Network previously) as one of the sites among three multinational sites. Study recruited 100 HIV negative women between August 2006 to April 2007. Safety and acceptability assessments were done. Researchers found both approaches equally safe and women's adherence to product use similar.
b. Expanded Safety Study of Praneem Polyherbal vaginal tablet among HIV un-infected women in Pune, India
The study was conducted between July 2004 between August 2005. This study was sponsored by National AIDS Control organization, India and conducted by National National AIDS Research Institute, Pune, India. This was randomized double blind placebo controlled trial to assess long term safety and acceptability of Praneem Polyherbal Tablet as a microbicide for short term use. They were given Praneem Polyherbal tablet to use intravaginally . Praneem Tablet contains purified extracts of dried leaves of Azadirachta indica (Neem tree) along with purified saponins from Sapindus mukerosi and Mentha Citrata Oil, Sodium Alginate as excepient and Citric Acid Monohydrate and Sodium Bi-Carbonate, as effervescent. 100 HIV un-infected, 50 were randomized in study product arm and 50 in the placebo arm. Participants were requested to use the study product at least half an hour before each sexual act for six months. Study involved 6 monthly visits. Safety was assessed at 3 monthly and 6 monthly visits. Acceptability was assessed by semi structured interview at 6 monthly visits. Praneem Polyherbal Tablet was safe for vaginal use up to 6 months with each act of sex among low risk women.
The study was conducted between April 2004 and January 2006. This study was sponsored by National AIDS Control organization, India and conducted by National National AIDS Research Institute, Pune, India. The objective was to assess preliminary safety and acceptability of Praneem Polyherbal Tablet as a microbicide for short term use. They were given Praneem Polyherbal tablet to use intravaginally once daily for 14 consecutive days. Praneem Tablet contains purified extracts of dried leaves of Azadirachta indica (Neem tree) along with purified saponins from Sapindus mukerosi and Mentha Citrata Oil, Sodium Alginate as excepient and Citric Acid Monohydrate and Sodium Bi-Carbonate, as effervescent.20 HIV sero-negative participants were enrolled in a phase I study. They were instructed to use the product intra-vaginally once daily at night for fourteen consecutive days between the menstruations. Clinical examination and laboratory diagnosis for STIs were done at screening, enrollment, day 7 and day 14 visits. Baseline colposcopic examination was done at enrollment and was repeated for local safety assessment on day 14. Acceptability was assessed through structured questionnaires at study exit. Praneem tablet was found to be safe and acceptable for once daily intra-vaginal use for 14 consecutive days in HIV uninfected female sex workers.
Publications:
Joshi S, Dutta S, B KK, Katti U, Kulkarni S, Risbud A, Mehendale S.Expanded Safety Study of Praneem Polyherbal vaginal tablet among HIV un-infected women in Pune, India: A Phase II clinical trial report. Sex Transm Infect. 2008 Apr 21.
Phase I safety and acceptability of Praneem polyherbal tablet among HIV uninfected female sex workers in Pune, India [in Press].
c. Phase I safety study of Praneem polyherbal vaginal tablet use among HIV-uninfected women in Pune, India.
The study was conducted between July 2003 and January 2004. This study was sponsored by National AIDS Control organization, India and conducted by National National AIDS Research Institute, Pune, India. The objective was to assess preliminary safety and acceptability of Praneem Polyherbal Tablet as a microbicide for short term use. 20 HIV negative, low risk and healthy women were recruited for the study. They were given Praneem Polyherbal tablet to use intravaginally once daily for 14 consecutive days. Praneem Tablet contains purified extracts of dried leaves of Azadirachta indica (Neem tree) along with purified saponins from Sapindus mukerosi and Mentha Citrata Oil, Sodium Alginate as excepient and Citric Acid Monohydrate and Sodium Bi-Carbonate, as effervescent. Colposcopy was done at enrollment and on day 14 and speculum examination on day 7 to assess the local toxicity. Acceptability was assessed with semi structured questionnaire and focus group diacussions with participating women and their male partners. Praneem Polyherbal Tablet was found to be safe and acceptable in once daily dose in low risk women after consecutive use for 14 days.
Publications:
Joshi SN, Katti U, Godbole S, Bharucha K, B KK, Kulkarni S, Risbud A, Mehendale S. Phase I safety study of Praneem polyherbal vaginal tablet use among HIV-uninfected women in Pune, India.Trans R Soc Trop Med Hyg. 2005 Oct;99(10):769-74. Joglekar NS, Joshi SN, Navlakha SN, Katti UR, Mehendale SM. Acceptability of Praneem polyherbal vaginal tablet among HIV uninfected women & their male partners in Pune, India--Phase I study. Indian J Med Res. 2006 Apr;123(4):547-52d. Phase I safety study of 0.5% PRO 2000 vaginal Gel among HIV un-infected women in Pune, India.
The study was conducted between July 2003 to March 2004 This study was sponsored by Division of AIDS .National Institute of Allergy and Infectious Diseases (NIAID), NIH and conducted by National AIDS Research Institute, Pune, India in collaboration with Johns Hopkins University, USA as a part HIV prevention trial Network. The study assessed safety and acceptability of PRO 2000 Gel which is an investigational vaginal microbicide based on a synthetic naphthalene sulphonate polymer that has been shown to be active against HIV. Forty-two eligible volunteers (30 low-risk and 12 high-risk) were given 0.5% PRO 2000 Gel for intra-vaginal application twice daily for 14 consecutive days. Safety was assessed colposcopically on enrollment (baseline), day 2 and day14 day and acceptability was assessed with semi structured interview and Focus Group Discussions. PRO 200 gel appeared to be safe and acceptable when used twice-daily by sexually active HIV-uninfected women from Pune, India.
Publications:
Smita J, Soma D, Beverly B, Albert P, JoAnn K, Fang G, Missy C, Lydia ST, Anjali P, Arun R, Sanjay M, Steven J R; HIV Prevention Trial Network (HPTN) 047 Protocol Team. Phase I safety study of 0.5% PRO 2000 vaginal Gel among HIV un-infected women in Pune, India. AIDS Res Ther. 2006 Feb 20; 3:4. Joglekar N, Joshi S, Kakde M, Fang G, Cianciola M, Reynolds S, Mehendale S; HIV Prevention Trial Network 047 Protocol Team. Acceptability of PRO2000 vaginal gel among HIV un-infected women in Pune, India. AIDS Care. 2007 Jul;19(6):817-21. Das Soma, Joglekar Neelam, Reynolds Steve, Joshi Smita. Experience of conducting a Phase I safety and acceptability clinical trial of a candidate vaginal microbicide 0.5% PRO 2000/5 Gel in Pune, India: Lessons learned" Accepted for publication In IJMR.e. Phase 1 trial to assess safety and acceptability of tropical Microbicide Buffer gel
The study was conducted between June 1998 and Dec 1998. This was a National Institute of Allergy and Infectious Diseases (NIAID), NIH funded HIV Network for Prevention Trial study conducted by National AIDS Research Institute, Pune, India in collaboration with Johns Hopkins University, USA as a part of multicentric, multinational HIVNET trial. Them product investigated was Buffergel which is a odorless and clear gel with a pH of 3.9. It buffers twice its volume of semen to a pH of approximately 5.0, maintaining the protective acidity of the vagina during and after intercourse. The study objective was to assess preliminary safety and acceptability of Bufferegl as a microbicide for short term use. 20 HIV negative, low risk and healthy women were recruited in two groups Sexually active (15) and sexually abstinent (5). They were given ‘Buffergel’ for vaginal use twice daily for 14 consecutive days between menses. Colposcopy was done at enrollment and on day 14 and speculum examination on day 7 to assess the local toxicity. Acceptability was assessed with semi structured questionnaire. BufferGel was found to be safe and well tolerated by the cervicovaginal epithelium and acceptable to the participants.
Publications:
Van de Wilgert J, Fullem A, Kelly C, Mehendale S, Rugpao S, Kumwenda N, Chirenje Z, Joshi S, Taha T, Padian N, Bollinger R and Nelson K. Phase 1 trial of tropical Microbicide Buffer gel Safety Results from four international sites. JAIDS 2001, 26: 21-7 Bentley ME, Fullem AM, Tolley EE, Kelly CW, Jogelkar N, Srirak N, Mwafulirwa L, Khumalo-Sakutukwa G, Celentano DD. Acceptability of a microbicide among women and their partners in a 4-country phase I trial. Am J Public Health. 2004 Jul;94(7):1159-64.f. Phase I safety & preliminary acceptability of nonoxynol-9 vaginal pessary as a vaginal microbicide in low risk women in Pune, India.
The study was conducted between January 1998 to June 1998. This was a National Institute of Allergy and Infectious Diseases (NIAID), NIH sponsored study conducted by National AIDS Research Institute, Pune, India in collaboration with Johns Hopkins University, USA The study objective was to assess preliminary safety and acceptability of nonoxynol-9 pessary as a microbicide for short term use. 23 HIV negative, low risk and healthy women were recruited in two groups Sexually active (18) and sexually abstinent (5). They were given ‘Today pessary’ containing 5 per cent of Nonoxynol-9 for vaginal use at bedtime for 14 days. Colposcopy was done at enrollment and on day 14 and speculum examination on day 7 to assess the local toxicity. Acceptability was assessed with semi structured questionnaire. Nonoxynol-9 vaginal pessary was found to be safe and acceptable in once daily dose in low risk women after consecutive use for 14 days. Willingness for future use, if found safe and effective for HIV prevention was shown by 8 (34.8%) women.
5. Study Title: Prevalence of HIV in Cutaneous Adverse Drug Reactions
This was a collaborative project between NARI and Dermatology department of Sassoon General Hospitals, Pune
Principal Investigator: Dr. Neeta Gokhale, Dr. Sunil Tolat, Dr. Damle (Dept of Skin & VD, SGH), Dr. Arvind, Dr. S M Mehendale
Study Duration: 2003 -2005
Design: Case control Study
Funding: NARI intramural study
Objectives:
Assess the HIV prevalence among the cases and controls
Describe the patter of adverse cutaneous drug reactions among persons of unknown HIV status presenting to this centre
Study Description:
This pilot study was initiated to see if drug rash can act as an indicator for HIV testing and was designed as a case control study. It is well known that persons infected with HIV are more likely to develop skin reactions to drugs. These drugs could be drugs used to treat opportunistic infections in HIV, antiretroviral drugs or any other drugs. This study was initiated to see if skin reactions to drugs may be an indicator for HIV testing. This could help in early diagnosis of HIV infection which is beneficial in clinical care of patient and would help in prevention too.
Cases:
All persons presenting to Skin department of Sassoon General Hospitals (SGH), who did not know their HIV status were included as cases in the study. Known HIV seropositive patients were excluded from the study.
Controls:
consisted of age and sex matched patients attending skin OPD who did not have HIV related dermatoses but were attending for other complaints.Participants received HIV pre and post test counseling, care and treatment for their skin complaints and CD4 test is done for all participants who test HIV positive. Skin Biopsy for histopathology is done after taking consent in a subset of patients.
Publications:
Manuscript in preparation
This was a collaborative project between Johns Hopkins University and NARI Pune
Principal Investigator: Dr. Sheela Godbole
Co-Principal Investigators: Dr. Amita Gupta JHU
Co-Investigators: Dr. Sanjay Mehedale, Dr. S.P. Tripathy, Dr.M. Ghate (NARI), Dr. R. Bollinger (JHU)
Study Duration: 2005 - 2007
Study Design: Pilot Survey
Objectives:
- To describe how health care providers are providing care and treatment of HIV-infected persons with particular emphasis on their experience with antiretroviral therapies
- To determine the availability of antiretroviral therapies and how pharmacies are providing these therapies.
Study Description:
208 health care providers and 204 pharmacists were surveyed using both self completed and interviewer administered survey tools. HCP and Pharmacists were sampled from four randomly selected electoral wards in Pune as well as from randomly selected private hospitals listed in the PMC registration list and from public dispensaries/hospitals under the jurisdiction of the PMC. Official Lists from Chemists’s association’ was used for pharmacists survey. A detailed questionnaire that included questions about provider characteristics, provision of HIV care and treatment , and referral patterns was be administered to consenting providers. Additionally self completed self assessment of confidence and an objective knowledge test assessing knowledge about HIV prevention, and management were alsoadministered.
Pharmacists were surveyed with a short questionnaire that included questions about what is available on their formulary and how it is provided to patients , attitudes of pharmacists as well as a test of knowledge related to ART and HIV.
Publications:
Abstracts:
Self-assessment identifies training needs in HIV care and management among Allopathic and Non-Allopathic Health Care Providers in Pune, India. Accepted for poster presentation at the XVIIth International AIDS Conference, being held at Mexico, 6 August 2008 Authors: S Godbole, S Mehendale, S Sane, R Bollinger, A Gupta
National AIDS Research Institute, Pune All rights reserved.