Observational HIV Studies Programme in Rural Uganda / Clinical Cohort Project

Lead Research Organisation: MRC/UVRI Uganda Research Unit on AIDS

Abstract

The clinical course of HIV infection seems to some extent to be different between industrialised and developing countries. Clinical data on HIV infection in Africa have mostly become available from research conducted at urban hospitals. Few clinical data are available from rural parts of Africa. Data on the natural course of the infection from its onset are even scarcer. Research is required to understand the natural course of the disease in the context of rural Africa, and in particular the nature of opportunistic infections and other disorders that define AIDS in this environment. Such data are needed to optimise treatment guidelines and to plan health interventions. Data on survival after the time of infection are also of interest for epidemiology and for epidemiological modelling. Since 1990, MRC has been following a clinical cohort of HIV infected patients that reside in an area where the MRC keeps a population of 25 rural communities under surveillance (as described in another abstract). Patients are regularly examined, and observations are recorded. An HIV-negative control group is also included, in order to provide information on background disease patterns and mortality. All study participants are treated whenever ill. This Rural Clinical Cohort (RCC) has provided very detailed insights in the natural course of HIV infection and its disease manifestation. In recent years, more effective drugs have become available to treat HIV infection. Such antiretroviral therapy (ART) can drastically reduce HIV in the blood and the tissue, and reinstall the competence of the bodys immune response to other infections and to HIV associated cancers. In industrialised countries, ART has been shown to have a strong positive impact on the survival and the general health of HIV infected patients. It has initially been unclear whether in the African environment (that is characterised by a great variety of additional health problems), and in particular in rural Africa where the majority of Africans live, similar successes may be possible. Another concern is what effect successful ART provision may have on sexual risk taking. It is also not clear to what extent the required adherence to ART will be possible in areas in which it is not easy for the population to attend regular clinical appointments. Such appointments are required to re-supply drugs and to check patients for side effects. Research is needed to establish whether ART can be effective in areas with limited infrastructure. ART has been introduced in the RCC in January 2004, and has since been provided to all study participants who are in need of it, both from the RCC and from the wider study population within which the RCC resides. The opportunity is used to investigate the research questions discussed above, and in particular to explore the effects of ART on the course of HIV infection and mortality, to identify problems with the provision and follow-up of ART, and to develop practical solutions. The RCC also provides an opportunity to contribute to the basic science research of the MRC in Uganda, for example in investigating which different types of HIV strains are circulating in the population, what their relationship is to HIV disease progression, and whether and how resistance to the drugs used for ART develops.

Technical Summary

Purpose: The project aims (1) to determine the rate of HIV-disease progression, including survival times to AIDS and death, (2) to describe disease manifestations, (3) to identify virological, immunological and other risk factors for progression, (4) to describe the impact of antiretroviral therapy (ART) on HIV related morbidity, mortality, transmission and behaviour in a rural African community. Data on the natural course of HIV infection in the context of rural Africa, and in particular the nature of opportunistic infections and other disorders that define AIDS in this environment are needed to optimise treatment guidelines and to plan health interventions. Data on survival after the time of infection are of interest for epidemiology and epidemiological modelling. Data are also required on the effectiveness of ART in the rural African environment with its limited infrastructure; and on its possible effects on sexual risk taking. Methods: The cohort: In 1990, a random selection of the HIV-1 seropositive adults identified from the initial survey round of a Rural General Population Cohort (GPC) in SW Uganda (see separate abstract) were invited to enrol into a Rural Clinical Cohort (RCC). Thereafter, HIV seroconvertors identified during subsequent surveillance rounds of the GPC have been enrolled as incident cases. HIV seronegative controls have been randomly selected from the GPC and were also enrolled in the RCC. Since 2004, participants from the GPC who present with symptoms and are clinically or haematologically eligible for ART are also enrolled. Data collection has been continuing since 1990. Following written informed consent, participants attend a study clinic situated at the rural MRC field station every three months. On these occasions, they are seen by clinicians who administer a detailed medical and behavioural questionnaire and perform a physical examination. Routine laboratory tests include a full blood count, urine and stool analyses and microscopy to detect malaria parasites. A CD4 count is performed in HIV positive participants every 6 months and once per year in HIV negative participants. HIV viral load is determined once a year in HIV positive participants. Participants are also requested to attend the clinic for the investigation and treatment of any medical problems occurring between routine appointments. They are encouraged to use the MRC counselling services provided both at the clinic and in the community, in order to obtain their HIV status. Data management and analysis are performed by the Statistics Section at the main MRC office in Entebbe. ART related research: Since January 2004, we provide antiretroviral treatment (ART) to participants already enrolled in the RCC and to participants from the GPC who qualify for ART according to Ugandan Ministry of Health (MoH) guidelines. Currently, first line treatment consists of a combination of zidovudine (AZT), lamivudine (3TC) and nevirapine (NVP), with possibility of switching to stavudine (d4T) in case of AZT toxicity and to efavirenz (EFZ) in case of NVP toxicity or concurrent tuberculosis treatment. Patients are intensively prepared through 3 counselling visits and a medical examination before starting on ART, and thereafter are seen at the clinic after 2 weeks, 4 weeks and then monthly. At baseline and every quarter, a detailed medical and sexual history and clinical examination are performed. Data are recorded on a pre-coded questionnaire. A full blood count is performed at baseline, at 1 month and every quarter. CD4 counts are performed at baseline and then 3-monthly, and liver and renal function tests at baseline, after 1 month, 3 months and then every 6 months. For research purposes, viral load is determined at baseline and every 6 months.

Publications

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Lieve Vd (2007) Effect of pregnancy on HIV disease progression and survival among women in rural Uganda. in Tropical medicine & international health : TM & IH

 
Description Poster presentation at the First Global Congress on Verbal Autopsy in Bali, Indonesia 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact The Global Congress was attended by over 100 participants

The Congress organisers requested to prepare a manuscript for publication in a special supplement for proceedings from the congress
Year(s) Of Engagement Activity 2011