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Lipodystrophy/Metabolic Complications of ART in South Africa
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Session 143 Complications of ART in Resource Poor and Developed Countries.
Tuesday, February 27, 2007
Carl J. Fichtenbaum, M.D. University of Cincinnati College of Medicine
There were 2 papers in this session addressing metabolic and related issues in resource poor settings. No real surprises reported here with significant toxicity observed with d4T based regimens resulting in lipid abnormalities and lipodystrophy. These articles continue to sound the drumbeat for eliminating d4T from regimens in the World when there are safer alternatives.
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 ³1 documented undetectable viral load after ART initiation. Of the total, 135 (44.1%) patients experienced ³1 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 effectsÑincluding peripheral neuropathy, lipodystrophy/lipoatrophy, and lactic acidosisÑnecessitated 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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Metabolic Complications of ART in Black South African Patients
Jaya George*, N Lutchman, and N Crowther
Natl Hlth Lab Svc, Univ of the Witwatersrand, Johannesburg, South Africa
Background: This 2-year longitudinal study is the first longitudinal study to look at metabolic effects of standard first-line therapy in African patients. Although several studies investigated similar effects in American and European patients, black patients are known to be metabolically different than white patients. In addition, the burden if HIV disease is in Africa, adding to the relevance of the study.
Methods: We report a 24-month longitudinal observational study conducted at the HIV clinic of the Johannesburg Hospital to investigate the effects of ART on metabolic parameters and body shape changes in black South African HIV+ subjects. We enrolled in the study 60 black patients attending the HIV clinic at the Johannesburg, of whom 43 completed it. Anthropometric and metabolic variables were measured every 4 months. These included body mass index, skin-fold thickness, fasting glucose, lipogram, insulin, and C peptide. Lipodystrophy was diagnosed from patient's own perception and physician observation of body shape changes. Statistical methods employed were multiple regression analysis, and t-tests.
Results: At the end of 2 years of follow-up, 39% of subjects on stavudine (d4T), lamivudine (3TC), and efavirenz (EFV) had developed lipodystrophy. Prior to initiation of ART these subjects had had higher body mass index (24.7±4.9 vs 22.3±3.2; p <0.05) and skin-fold thicknesses than subjects who did not develop lipodystrophy. After 1 year of therapy none of the subjects had developed lipodystrophy based on their perceptions or physician perception of body shape changes. Body shape changes were apparent after about 18 months of therapy. Subjects with lipodystrophy had significant increases above the baseline value for waist-to-hip ratio (0.79±0.04 to 0.86±0.10; p <0.01), glucose (4.25±0.41 to 4.68±0.62 mM) and triglyceride (1.11±0.77 to 1.45±1.12 mM; p = 0.07) levels whereas subjects without lipodystrophy did not. All subjects, irrespective of the development of lipodystrophy, had significant increases above baseline values for body mass index (23.3±4.2 to 25.1±4.0; p <0.0005) and serum levels of total cholesterol (3.64±0.95 to 4.59±1.18 mM; p <0.0001), cholesterol LDL (2.29±0.73 to 2.67±0.84 mM; p <0.01) and HDL (0.89±0.31 to 1.40±0.49 mM; p <0.0001). These data suggest that subjects who develop lipodystrophy have greater levels of body fat prior to ART than subjects who do not develop lipodystrophy and that in the former subjects ART causes increased waist-to-hip ratio, glucose, and triglyceride concentrations.
Conclusions: Standard first-line therapy in South Africa leads to increased body mass index and increased serum total, LDL and HDL cholesterol levels independently of any effects on body fat re-distribution. Patients with higher body mass index prior to initiation of ART are at increased risk for developing body fat changes. The risk of developing lipodystrophy increases with longer duration of therapy.
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