Complications of long-term antiretroviral therapy in Uganda. (CoLTART); a prospective Cohort Study

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

Abstract

There are few published papers on the clinical consequences of the clinical consequences of long standing treated HIV infection among Africans and since Antiretroviral therapy (ART) of HIV for is a recent clinical intervention in sub-Saharan Africa there is as yet little information on the long term impact of antiretroviral drugs (ARVs) and on the long term ARV drug toxicities among African populations.
One of the reasons for this is that few treatment centres in Africa have the capacity to routinely assess the required clinical and laboratory markers of ARV drug effect and complications.
Currently, ART practice guidelines in sub-Saharan Africa are based on information gathered from industrialised country settings, even though there are significant differences between industrialised countries and sub-Saharan Africa in terms of the profile of HIV infected patients, the background risk factors for HIV related infections and complications of long term HIV infection; and there are possibly also differences in individuals’ susceptibility to the toxic effects of ARV drugs.
In this 3 year cohort study, approximately 1400 HIV infected Ugandan adults, who have been on ART for up to 10 years, will be observed to document indicators of those long term effects of ART that are known, for example: effects of some of the ARVs on kidney function and the risk of heart disease. The effectiveness of HIV treatment among these patients will also be documented in relation to the types of ARV drugs that they have been treated with.
Studies such as this one, among African patients on long term ART, are required in order to inform evolving guidelines on the treatment of HIV infection within African populations.

Technical Summary

Widespread use of antiretroviral therapy (ART) for HIV infection is a relatively recent intervention in sub-Saharan Africa and there have been few studies on the clinical consequences of long term treated HIV infection or the long-term impact of antiretroviral (ARV) drug treatment or ARV toxicities among Africans.
CoLTART is a prospective cohort study aimed at documenting the occurrence of cardio-metabolic abnormalities and renal dysfunction among Ugandan patients on long term ART, and at assessing outcomes of ARV treatment in relation to type of the initial ARV regimens used.
Participants in the prospective cohort will be drawn from 2 existing MRC cohorts and will comprise approximately 742 patients who initiated ART within the MRC funded DART trial and 597 patients of the MRC rural clinical cohort (RCC) who have cumulatively been on ART for 8-10 years. Data collected from the prospective follow up will be supplemented by available retrospective / historical clinical data collected during and after the DART trial and within the RCC.
At quarterly review, each cohort participant will be assessed for occurrence of clinical events, and for biochemical markers of renal and cardio-metabolic function as well as immunological and virological markers of treatment effect.
The primary objectives of CoLTART are:
1. To compare mean values for Cardio-metabolic markers (serum cholesterol, HDL, LDL, triglyceride and blood glucose levels) and mean blood pressure among patients on a Protease Inhibitor (PI)-containing ART regimen and those on a non PI-containing ART regimen.
2. To compare mean values of markers of renal function renal function tests (creatinine clearance, estimated Glomerular filtration rate, renal phosphate clearance) among patients on a tenofovir (TDF) containing ART regimen and those on a non-TDF containing ART regimen.
3. To compare the time to failure of the 1st line ARV regimen and immunologic response (CD4 trajectory over time) among patients who were initiated on a triple nucleoside ARV regimen and those who were initiated on a standard (2NRTI / 1 NNRTI) first line ART regimen.
Exploratory objectives of CoLTART will examine:
- Factors associated with the metabolic outcome variables and markers of renal dysfunction and whether the effect of any of these factors is modified by the type of ART regimen.
-Whether there is an association between the presence of metabolic abnormalities or renal dysfunction and immunological outcomes of ART, treatment failure or death.
Data from this study will be useful to inform evolving practice guidelines in the wider ART access programs of the region, specifically, rational choice of ART regimens and the detection and management of ARV related toxicities.

Publications

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