795 
High Rates of Non-fatal Toxicities in a 24-Month Cohort Receiving Publicly Funded HAART in South Africa
Emily B Wong*1, D Murdoch2, J Wing3, C Feldman3, and W Venter4
1Univ of California, San Francisco, US; 2Duke Univ Med Ctr, Durham, NC, US; 3Univ of the Witswatersrand, Johannesburg, South Africa; and 4Reproductive Hlth and HIV Res Unit, Johannesburg, South Africa
Background: In April 2004, publicly funded ART in South Africa
was rolled-out using stavudine (d4T)+lamivudine (3TC)+efavirenz (EFV) as
the first-line combination for treatment-naive, non-pregnant adults. There is
little literature on the rates of side effects of this regimen in a Sub-Saharan
African population.
Methods: To characterize the long-term side effects of
this regimen, we performed a retrospective chart review of the first 305
treatment-naive, non-pregnant adults who initiated ART at a large publicly
funded clinic in Johannesburg.
Demographic information, tuberculosis and opportunistic infection history,
weight, CD4 count, viral load, and complications were recorded over 24 months
of therapy. Statistical analyses were performed with STATA v8.2.
Results: The mean duration of follow-up for 305
patients was 1.49±0.58 years, with a total of 445 patient-years of follow-up. Mean
CD4 cell count increased from 95±73 to 245±121 cells/mm3, mean
weight increased from 61.7±12.8 to 64.1±11.7 kg, and 81.3% of patients had ≥1
documented undetectable viral load after ART initiation. Of the total, 135
(44.1%) patients experienced ≥1 treatment-related side effects, yielding
an incidence rate of 30.3 events/100 patient-years. The most common side
effects were peripheral neuropathy (n
= 97, 31.8% of all treated patients), lipodystrophy (n = 26, 8.5%), gynecomastia (n
= 27, 8.9%), lipodystrophy/lipoatrophy (n = 26, 8.5%), and lactic acidosis (n = 20, 6.6%). Treatment limiting side
effects necessitated ART regimen change in 60 (19.7%) patients. On average,
regimen changes occurred after 14.5±7.4 months of therapy. During the follow-up
period there were 17 (5.6% of all treated patients) deaths, 2 of which were
attributed to fatal toxicities of ART (1 to lactic acidosis, and 1 to fulminant
hepatitis).
Conclusions: Although publicly funded ART treatment in
South Africa is associated with low mortality and favorable clinical and
immunological responses, significant non-fatal adverse effects—including peripheral
neuropathy, lipodystrophy/lipoatrophy, and lactic
acidosis—necessitated a regimen change in one-fifth of patients initiated on
d4T+3TC+EFV. These findings support the recently revised WHO guidelines for ART
therapy in resource-limited settings that caution against the toxicities of d4T-containing
regimens.
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