Metabolic Complications of HAART in a South African Black Population

Nombulelo Princess Magula, Umesh Lalloo

Abstract


The clinical and immunological benefits of HAART in patients infected with the human immunodeficiency virus (HIV) appear to be associated with changes in metabolic function and body composition described as lipodystrophy. A wide variation in reports of prevalence (20-84%), incidence, severity, risk factors and responses to interventions has been attributed to a lack of an objective case definition of lipodystrophy.

HIV-related lipodystrophy is a term that has been used to collectively to describe fat accumulation (lipohypertrophy), dyslipidemia, insulin resistance and an associated subcutaneous fat wasting (lipoatrophy). The Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) recently proposed a new methodology for evaluating the individual components of lipodystrophy. FRAM was initiated in the United States in 2000 to evaluate the prevalence and correlates of changes in fat distribution, insulin resistance and dyslipidemia in a geographically and ethnically diverse population of infected with HIV compared with controls.

This HAART related complication emerged in resource-rich countries soon after the introduction of HAART. Initially lipodystrophy was attributed to the use of Protease Inhibitors (PI). However there were subsequent reports in patients that were treated with Nucleoside Reverse Transcriptase Inhibitors (NRTIS), particularly the thymidine analogues. Thymidine analogue NRTIs such as stavudine is now avoided in resource-rich countries as a strategy to reduce metabolic and other related complications. Current treatment guidelines in South Africa recommend the use of thymidine analogue NRTIs that include stavudine. There is poor access to non-thymidine analogue NRTIs.

Other metabolic complications that may be associated with the lipodystrophy syndrome include asymptomatic hyperlactatemia, bone demineralization and rarely, symptomatic lactic acidosis. Metabolic complications associated with HAART may lead to increased risk in morbidity especially cardiovascular disease. The signs of lipodystrophy usually appear progressively over an 18 to 24 months period. The interplay between HAART, HIV and host factors may explain why some patients develop lipodystrophy while others are spared.

It is hypothesized that lipodystrophy (lipo-atrophy, fat accumulation, insulin resistance and dyslipidemia ) and associated metabolic complications is common in Black patients receiving HAART and may be genetically pre-determined.

In order to prove this hypothesis, this study will employ the FRAM instruments and it will be conducted in two steps. Step 1 will be a cross-sectional design that will determine the patterns of fat distribution and prevalence of lipodystrophy in a group of healthy HIV-infected, HAART nave subjects (study group) and an age, gender and body mass index matched, healthy non HIV-infected subjects (control group). Step 2 of the study will be a prospective cohort design that will evaluate the incidence of lipodystrophy and associated metabolic complications in a cohort of Black patients who are HAART nave, commenced on HAART within the South African Antiretroviral Treatment Rollout Program and followed up for at least 24 months. This study will examine pathogenic mechanisms for the development of the individual components of these metabolic complications in this population.

The significance of this study is that the prevalence and incidence of these metabolic complications remain unknown in resource-constrained settings. Knowledge gained from examination of the pathogenic mechanisms of these complications will contribute to designing treatment strategies for reducing or effectively managing these treatment related complications