The role of stavudine in the South African public sector antiretroviral programme: Should the perfect be the enemy of the good?

Abstract

Stavudine (d4T) was one of the first nucleoside analogues developed as an HIV antiretroviral (ARV). An early monotherapy trial demonstrated similar antiviral activity to zidovudine (AZT), and a comparative study of d4T and AZT in combination with lamivudine (3TC) and a protease inhibitor(PI) reported similar therapeutic outcome in each randomised treatment arm. Since registration in 1993 by the US Federal Drug Agency, d4T has been used extensively in combination therapy and was one of the first ARVs to become available in South Africa as a generic formulation. There is recently published evidence that its use is associated with higher CD4 cell count responses than other nucleoside analogues. The generic formulation with 3TC and nevirapine (NVP) is currently the cheapest ARV combination therapy available worldwide. With the development of a necessary public health approach to expanded access to ARVs in resource-poor settings the World Health Organization (WHO) included d4T in its recommended first-line ARV regimens. Following widespread use of d4T, adverse events including lipodystrophy, neuropathy and lactic acidosis associated with long-term therapy have been increasingly recognised. Despite the proven utility of d4T in more than a decade of use and its very low cost there has been an increasing swing of medical opinion against use of d4T and a search for alternatives.