HIV/AIDS related research

Research Plan: Epidemiological studies of the causes of HIV-1 in low income countries.

Non-Technical Summary:
HIV-1 transmission studies in low income settings. We have performed a meta-analyses of exiting studies from Africa and India of risk factors for HIV-1, quantifying the risks of sex work contact, sexually-transmitted infections (STI), male circumcision, condom use and alcohol abuse.  CGHR has been working closely with the Indian government and our academic partners in India to carry out a set of studies to better understand India’s HIV epidemic.  A great deal of this analysis is complete, and we are in the process of proposing to repeat these analysis in other low income countries with both high and low HIV-1 prevalence. 

Background: Purpose of the Proposed and Ongoing Research
The 20th century has seen unparalleled achievements in global health. Life expectancy in the last 40 years has improved more than in the preceding 4,000 years. Ensuring that these remarkable gains extend to the 21st century requires control of a few major diseases, with specific attention to the two large and growing causes of deaths worldwide: HIV-1 and tobacco. HIV/AIDS has already killed over 20 million people; 40 million people are infected with the virus, and the infection continues to spread unabated in many countries. HIV-1 has already reduced life expectancy in sub-Saharan Africa and it may soon do so in India and other parts of Asia. The growth in the HIV-1 epidemic is uncertain, and it may well kill several hundreds of millions of people in this century.

Epidemiological studies on the consequences of HIV-1 infection are required to raise public knowledge and to guide control programs. Targeted interventions must be knowledge based; the evidence from these epidemiological studies will guide these programs to be more efficient and effective in decreasing HIV-1 transmission.

Proposed Research Activity:

Our focus to date has been on the epidemiology of HIV-1 in India.  There are over 5 million people infected with HIV-1 in India, ranking second only to 5.3 million infected in South Africa. “With a population of 1 billion, large numbers of commercial sex workers, mobile male workers, a high prevalence of STDs, low reported condom use with non-regular partners and a low prevalence of male circumcision, India is set to experience an explosion of HIV- 1 cases.” (CMAJ, 2004).  Our efforts are therefore geared towards understanding the transmission dynamics and providing evidence for targeted interventions.  We have used data from a variety of sources including antenatal clincs (ANCs), Voluntary counseling and treatment clincs (VCTCs), sexually transmitted infection clinics (STIs), and surveys including the Reproductive and Child Health Rapid Household Survey (RCH), and the Behavioural Surveillance Survey (BSS).

Below is a list of the studies we have completed or are in the process of completing.

A. Population levels, trends and determinants of HIV prevalence

1. Trends in HIV among 300,000 antenatal clinic attendees in North and South India.
   • This study was published in the Lancet in March 2006 and is the world’s largest published study of HIV among a routine resting population. The study documents a 30% decline in HIV prevalence from 2000 to 2004 among young women in the South. This is most likely due to increased condom usage between male clients of female sex workers.

2. HIV prevalence among urban and rural antenatal clinics in North and South India.

This study will examine differences in HIV levels, trends and determinants of infection between urban (n=100,000) and rural (n=49,000) India using two different definitions of residence; one site-based and one individual-based.

3. Trends in HIV prevalence among 120,000 male and female sexually transmitted infection (STI) clinic attendees in North and South India.

·        This study documents changes in HIV prevalence among males with genital ulcer from 2000 to 2004. Genital ulcer among male STI clinic attendees is a marker for recent high-risk sex contact and helps document changes in male sexual behaviour.

4. Geographic analysis of HIV in 115 districts of South India.
   • There is a substantial geographical heterogeneity of HIV prevalence existing within the 115 districts of the 4 states analyzed. Our findings are robust with respect to the specification of the prior distribution. Prevalence of STDs in the previous year and average age at marriage are significantly associated with district-wise HIV infection. Spatial mapping will be used to quantify locality and risk of HIV infection.

5. Ecological Study of HIV-1 in 115 Districts in 4 Southern States of India
   • This study examined the differing risk factors on an ecological level in 115 districts in 4 high prevalence southern states of India: Andhra Pradesh, Karnataka, Maharashtra and Tamil Nadu.

6. Measurement of AIDS mortality from a large scale representative community-based national household survey.
   • Part of a much larger cohort study called the “Million Death Study” that aims to document causes of death in 1.3 million households (approximately 7.6 million people) from 2004 to 2014

7. Meta-analysis of behavioural and sexual risk factors for HIV in Africa

·        The study synthesizes evidence from 79 studies done in African countries and provides strong evidence that commercial sex work multiple sex partners, HSV-2 and male lack of circumcision were significantly associated with HIV infection. The meta-analysis will be expanded to Asia. (link to be posted soon)

8. Review of Behavioural Surveys in India.
   • We have systematically analyzed data from over 25 behavioural surveys covering more than 100,000 adults at high-risk of HIV infection (female sex workers and their male clients) and at lower risk (general population). These analyses will help us better understand sexual networks in India. (link to be posted soon)

B. Improved tools for population-based HIV measurement

9. Risk of HSV-2 infection among general population survey subjects.

• We aim to use HSV-2 as a marker for high-risk sexual activity in our general population survey of 3,000 adults to improve validity of sexual behavioural surveys. We are in talks with biotech firms to develop a “risk chip”. This bloodspot-based technology would yield results for an individual’s HIV status, including incident versus prevalent infection, and status of an STI such as HSV-2.

10. Comparative study of demographics of ANC attendees and the Indian general population from the reproductive child health survey.

·        A large proportion of women in India utilize private ANC services. HIV sentinel surveillance among pregnant women in India draws from only public ANCs. We are studying ANC public versus private usage behaviour among general population women in India to assess validity of HIV estimates of prevalence and trends.

11. Audio-assisted confidential voting interview to improve validity of data on sexual risk taking behaviour from community based surveys.
    • In low literacy setting, audio assisted confidential voting interview method may extract more valid information related to sexuality than the conventional face to face interview or the self administered questionnaire.

12. HIV prevalence and risk factors among 30,000 voluntary counselling and testing centre (VCTC) attendees in Tamil Nadu, India.
    • A descriptive analysis of the population attending VCTC services. Marked heterogeneity exists in reason for attending. We are attempting to characterize HIV risk sub groups within this high-risk self-selected population.

C. Policy and programmatic impact

13. Comprehensive mathematical model of HIV transmission in India

·        Our comprehensive model suggests almost all of the new HIV-1 infections arise from first or second generation exposure to FSWs. The most practical and effective intervention is to increase the rate of condom use. We are currently working on modeling the effects of a HIV-1 vaccine, with and without disinhibition, a Herpes Simplex Virus 2 (HSV-2) vaccine, male circumcision and the population impact of antiretroviral roll-out.

14. Monitoring and evaluation of HIV sentinel surveillance system expansion in India

• A pilot project in five sentinel surveillance sites in both the north and south of India to evaluate ways in which a few simple low cost improvements to the surveillance system in the behavioural questionnaire and biological testing could greatly improve explanatory power of routinely collected data

15. Qualitative examination of uptake of information from the Ecological Study

·        This study aims to determine whether the provision of evidence for preventative HIV interventions to policy makers and program officers at the district and state level translates into programmatic changes. The study also includes a two day Workshop aimed at information dissemination to key policy makers and NGOs involved in targeted interventions in India.

Impact:
The 21st century may well see most people living to old age if they can avoid the few major causes of death today, specifically HIV-1 and tobacco. These epidemiological studies are unique, large and of high quality and impact; the HIV-1 transmission studies will be central to understanding the spread of HIV-1 in low income settings, and thus will guide effective control programs. The studies will strengthen analytic capacity within Canada for large-scale population-based epidemiological research.

Because of the success of the HIV-1 studies in India to date, there is interest from several additional low income countries to replicate our epidemiological studies.