HIV Care Research Programme / Follow up of slow disease progressors and of individuals on long term ART

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


A group of about 700 patients was recruited who have been on ART for up to 7 years. This unusual follow-up group provides an opportunity to address questions about the long term effects of ART with respect to HIV disease and treatment side effects. Such effects may differ from those seen in the North because of genetic characteristics, type of ART regimen received, differences in treatment adherence, or due to other diseases typical for Africa. We will also make use of this group for a trial to investigate the safety of stopping cotrimoxazole prophylaxis in patients doing well on ART (this is a drug that prevents bacterial infections in patients with weak immune system and may no longer be needed in patients who regained their immunity due to ART). We will also explore whether nurses (rather than doctors) can provide routine follow up care for ART patients (which would be important for areas where there is no doctor), or whether larger intervals between drug refills (e.g. 3 months versus 1 month) are safe in managing patients. - We also keep regular contact with patients who have been HIV infected for a long time, but who are still well and do not need ART yet. This group is important for research on the immunological factors that may protect individuals from becoming HIV infected at all or infected individuals from experiencing fast diseases progression. Such knowledge may be helpful for the design of an effective vaccine against HIV infection.

Technical Summary

In 2009, a well characterised cohort has been established at the MRC/UVRI Uganda Unit in Entebbe of about 700 HIV-infected patients who have been receiving anti-retroviral therapy (ART) for 5 years or more, with some on ART since 2003. Most of these patients had formerly participated in the international DART trial. Researchers from the DART research centres in Uganda and Zimbabwe agreed to maintain follow up of DART study participants and collect compatible data so that the various former DART sub-cohorts continue to provide good quality longitudinal data to inform ART treatment policy in Africa. Together they form one of the longest standing ART cohorts in the continent. The Entebbe project also comprises an additional group of about 100 infected individuals who have been diagnosed with HIV infection more than 5 years ago, but whose disease progression is very slow and who do not require ART yet. Patients in this population are seen at clinic every 3 months. For the long-term ART group, the objective is to study (i) the outcomes of 1st line ART up to 10 years, in terms of rates of treatment failure necessitating a switch to 2nd line ART (after 5 years, 19% of DART patients in Uganda had switched to 2nd line ART, how this proportion changes over time is important information for ongoing ART programmes); (ii) the possible long-term toxicities of 1st line ART in African populations; (iii) the medium-term impact of the boosted protease inhibitor class which is currently widely introduced in Africa as the mainstay of 2nd line ART (protease inhibitors may have a different toxicity profile in Africans compared to populations of industrialised countries, due to different dietary and other risk factors for the established cardiovascular and metabolic complications of this drug class; (iv) the durability of this 2nd line ART regimen; (v) the long term impact of initiating ART with a single class (3NRTI) regimen as used for many patients in DART (initiating therapy with a 3NRTI regimen was uniquely implemented in DART and has the advantage of preserving 2 ART drug classes; (vi) whether the good adherence to 1st line ART as observed in DART will be maintained outside of a trial situation and which factors are associated with good long term adherence; (vii) the development of viral resistance among patients who have not been managed using real time viral load; and (viii) the pattern of morbidity and mortality among patients with long term ART in Africa. Part of the cohort will provide a valuable resource for the MRC funded COSTP trial, that will investigate whether cotrimoxazole prophylaxis can be safely discontinued among patients who have regained their immune-competence on ART. The sub-cohort on long term progressors will continue to provide valuable data and blood specimens in support of the Units Basic Science Programme research on immunological characteristics that may be helpful for vaccine development.


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Walker AS (2012) Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Description Uganda National Council of Science and Technology 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact National consultative meeting of research and medicines regulators to discuss ethical appropriateness of further trials on cotrimoxazole prophylaxis among HIV infected patients on antiretroviral therapy. We provided data on effect of Cotrimoxazole on haematologic parameters of untreated HIV infected adults.

A call was made for further studies evaluating continued prophylactic treatment with Cotrimoxazole for HIV infected patients on antiretroviral therapy
Year(s) Of Engagement Activity 2008