Quantitative assessment of the prevalence of mitochondrial toxicity in HIV/AIDS patients initiated on a stavudine containing regimen in Mount Ayliff Hospital ARV clinic

Abstract

Since the introduction of Anti-Retroviral Therapy (ART) worldwide, Human Immunodeficiency Virus (HIV)-related morbidity and mortality has reportedly improved for many People Living With HIV/AIDS (PLWHA). The treatment of HIV/AIDS (Acquired Immune Deficiency Syndrome) consists of taking a combination of three or more antiretroviral drugs (ARVs) known as Highly Active ART (HAART). Chronic administration of HAART can lead to various adverse events that include mitochondrial toxicity which not only impacts adherence to therapy, but also patient safety. Mitochondrial toxicity has been most commonly associated with stavudine (d4T). Mitochondrial toxicity may manifest as peripheral neuropathy, lactic acidosis/hyperlactatemia and lipoatrophy. The South African ART guidelines launched in 2004 uses d4T as part of the first line HAART regimen in the management of HIV/AIDS [National Department of Health (NDoH), 2004]. This is a retrospective study of 803 enrolled HAART-naïve adult patients initiated on a d4T-containing regimen between January 2006 and June 2009. The aim of the research was to quantitatively assess for the prevalence of mitochondrial toxicity as a result of d4T use in their individual regimens. A total of 120 (14.9%) of the study population (803) experienced peripheral neuropathy, with the majority reporting peripheral neuropathy within 6 months (median 5.9 months) after d4T initiation. Twelve patients on concurrent anti-TB drug treatment complained of increased severity of peripheral neuropathy with d4T use. The blood lactate level of 70 patients were reviewed, 18 (8.7%) of the study population had lactate levels > 2.2mmol/l. Fourteen patients (1.7%) of the study population experienced lipoatrophy. The mean duration before developing hyperlactatemia was 21.8 months (SD± 7.6) and 24.5 months (SD± 7.3) for lipoatrophy. An awareness of the early detection of symptoms associated with mitochondrial toxicity is useful to enable optimal clinical outcomes, and support adherence and compliance to therapy. In-service training of clinicians in pharmacovigilance protocols may also be improved. Since 2010, Tenofovir has been added to the first line regimen, and although d4t is no longer the first line ARV of choice, a large number of patients are still being maintained on a d4t-containing regimen. Finally, this research may be used in assessing the risk profile for patients being initiated on NRTI based regimens.