Fat loss caused by the d4T (stavudine) component of triple antiretroviral therapy is beginning to trigger treatment changes among people receiving HIV treatment in South Africa, doctors from Durban’s McCord Hospital reported at last week’s 2006 Implementers Meeting of the President’s Emergency Plan for AIDS Relief in Durban, South Africa.
These data are the first substantial indicator from southern Africa that fat loss due to d4T is a problem for African patients. The study, reported by Jane Hampton of McCord Hospital, showed a switch rate of 73 cases per 1000 patient years of follow-up.
Previous data from Cape Town, presented at the Thirteenth Conference on Retroviruses and Opportunistic Infections earlier this year, had suggested that switching from d4T-based treatment due to lipodystrophy was uncommon. The study found an unexpectedly high incidence of lactic acidosis, a life-threatening side-effect of d4T treatment, especially among women with a higher body mass, and led in part to the publication of guidelines by the Southern African HIV Clinicians Society on monitoring and managing patients at risk of lactic acidosis.
The McCord Hospital study reported data from 2323 patients who had initiated antiretroviral therapy at its Sinikithemba clinic since 2004. Just over eight per cent had died after beginning treatment, 3.8% were lost to follow-up and 8.9% had changed treatment centre.
The predominant regimen prescribed was d4T/3TC/efavirenz. The cohort had accumulated 1204 patient years of treatment with d4T, while 2022 had received treatment with efavirenz, 290 with nevirapine and 330 with AZT in their first-line regimen.
The most common reason for a switch of treatment was peripheral neuropathy caused by d4T, which caused 160 switches (56% taking place between months 6 and 12 of treatment).
A total of 40 cases of hyperlactatemia (lactate levels above 5mmol/l) were observed up until March 2006. Twenty-six cases were observed up to July 2005 (two men, 24 women), leading to four deaths, an incidence rate of 37 per 1000 patient years of d4T treatment. This compares with an incidence rate of 15 cases per 1000 patient years of follow-up in the Cape Town cohort, although the two groups may not be strictly comparable.
No further deaths occurred after July 2005, when new guidelines on starting treatment were introduced. Women with a body mass index above 28 (the highest risk group for developing lactic acidosis among South African patients) would henceforth start treatment with AZT/3TC rather than a d4T-containing regimen, whilst women with a BMI above 28 already receiving d4T would be switched to AZT and given dietary advice in a bid to reduce their weight. No cases of hyperlactatemia have occurred in those who have received AZT or switched to it.
Ninety-seven patients switched from d4T due to lipodystrophy, a rate of 73 switches per 1000 patient years. Fat loss manifested more commonly in the buttocks and thighs than in the arms or face among women. Changes were a consequence not only of fat loss, but of fat accumulation too. Twenty-three women who switched treatment experienced breast enlargement and 19 experienced abdominal fat accumulation, but no details were available to describe whether these women had received efavirenz-containing regimens.
The study’s authors say that the documentation of side-effects and reasons for switching treatment is necessary in order to inform policy makers, and that the choice of ARV drugs presently used in South Africa will need to be reconsidered.
Further discussion of serious side effects in resource-limited settings can be read in HIV & AIDS Treatment in Practice, NAM's electronic newsletter on HIV treatment in resource-limited settings.
Hampton J et al. ART side effects resulting in a change of regimen in a cohort of patients treated at McCord Hospital, Durban, KZN, South Africa. The 2006 HIV/AIDS Implementers Meeting of the President’s Emergency Plan for AIDS Relief, Durban, South Africa, abstract 488.