d4T dose reduction does not result in poorer treatment outcomes in South African patients

The use of a reduced dose of d4T (stavudine), as recommended by the World Health Organization, did not reduce the likelihood of viral load suppression after six months in a large cohort of South African patients, researchers from the Aurum Institute of Health Research report in the August 24th edition of AIDS.

The use of d4T in first-line treatment has been phased out in the developed world due to toxicity, but in developing countries fixed-dose combinations containing d4T are still widely used due to the drug’s low cost compared to tenofovir or abacavir. In South Africa d4T remains a staple component of first-line treatment in the public health system, despite widespread calls for its use to be phased out.

The key toxicities associated with d4T are lipoatrophy (fat loss), hyperlactatemia and lactic acidosis, and peripheral neuropathy.

The drug was originally licensed at a dose of 40mg twice daily in adults weighing more than 60kg.

In 2007 the World Health Organization recommended that developing country treatment programmes should use a 30mg dose of d4T if it was not possible to phase out use of the drug. Their recommendation was based on a number of small studies which showed no negative effect of using a lower dose in adults weighing more than 60kg.

Adoption of the 30mg dose has been slow in some national programmes, and data are still lacking from an African population on the virological effects of initiating therapy with a lower dose of d4T.

Researchers at the Aurum Institute in Johannesburg analysed data from 618 patients enrolled in community-based HIV care programmes in South Africa who initiated treatment containing d4T between January 2006 and January 2008. All patients had been followed for at least six months after starting treatment, and weighed at least 60kg at baseline.

Of the eligible patients, 110 received a 30mg dose and 508 received a 40mg dose. Those receiving a 30mg dose were slightly more likely to receive nevirapine than efavirenz and to have WHO stage 4 HIV disease, and had significantly lower baseline CD4 counts (91 vs 115, p=0.0001). These differences were not a result of individualisation of treatment, say the investigators, but due to a change in guidelines during the period under study.

There was no significant difference after six months of treatment in the proportion of patients who had viral load below 400 copies/ml or 50 copies/ml (79% vs 81% and 60% vs 58% respectively). Multivariate analysis which adjusted for NNRTI agent, baseline viral load and weight showed no effect of dose on viral suppression.

The investigators say their findings provide additional evidence to support the WHO recommendation, but note that evaluation of long-term side effects according to dose is essential.