Effect of toxicities to triomune on virologic outcomes among HIV-1infected adults at the Infectius Diseases Insititute, Uganda

Abstract

Introduction: Use of fixed dose generic combination of stavudine, lamivudine and nevirapine (Triomune) for the treatment of HIV I AIDS is wide spread in Resource Limited Settings (RLS). However, the clinical benefits of these drugs may be limited by associated toxicities. The factors associated with Triomune related toxicity and the effects of these toxicities on virologic outcome are not well studied in Uganda, a RLS. Objectives: To establish the factors [demographic, clinical and laboratory] associated with selected Triomune related toxicities (peripheral neuropathy, skin rash, liver injury and hyperlactaemia) and the effect of these toxicities on virologic outcome during the first year of treatment among HIV-1 infected adults at Infectious Diseases Institute (IDI) Mulago. Methodology: This was a retrospective cohort study using the database and patient records from an earlier established cohort of consecutively enrolled HIV-infected adults at the IDI between April 2004 and April 2005. Univariate and multivariate analysis was used to compare demographic, clinical and laboratory characteristics at baseline of patients who developed toxicity and those who did not develop toxicity. Results: Three hundred eighty eight patients were included in this study of which 73% were female. The median age was 37 (IQR= 32- 44) years, median BMI was 20 kg/m2 IQR (18-22). In addition most of the patients had advanced HIV disease (92% WHO stage 3 or 4), median CD4 count of 91 (IQR= 14-158) cells/mm3 and a high median viral load (VL) [5.410glO (IQR= 5.1-5.7)] copies / ml. A total of 146 (36.9%) patients developed at least one of the selected toxicities during the first year of therapy, with peripheral neuropathy (PN) as the most frequent toxicity. Over weight patients (BMI above 25kg/m2) were almost six times more likely to develop toxicity as compared to the underweight patients OR 5.69 (95% CI 2.33-14.2) P = < 0.001 Patients with haemoglobin concentration below 11.5g/dl were twice as likely to develop toxicity as patients whose haemoglobin concentration was above 11.5g/dl [OR = 1.92 (95% CI: 1.25-2.96) p = 0.002]. Patients who were treated with 40mg of stavudine had twice the likelihood of developing toxicity compared to patients treated with 30mg [OR 1.96 (95% CI: 1.24-3.49) P = 0.003]. However, patients whose self- reported adherence above 95% were not more likely to develop toxicity than those who replied less adherence. A baseline CD4 count above 200 cells/mm OR 2.39 (95% CI 1.18-4.84) p = 0.015 and a viral load more than 5 10glO copies OR 1.82 (95% CI, 1.01-3.26) p = 0.04, were associated with occurrence of PN, while baseline CD4 count below 100 cells/ml OR 3.27 (95% CI 1.60- 6.68) P = 0.001 was associated with liver injury. Of the 306, patients with complete data at 12 months, 86.6% had virologic suppression. There was no significant difference in virologic suppression among patients who developed any toxicity compared to patients who did not develop toxicity. Conclusions: In this cohort, development of toxicity to Triomune had no effect on virologic outcome. There was a high incidence of toxicity especially peripheral neuropathy. Being over weight, having low haemoglobin concentration and receiving 40mg of stavudine were associated with increased likelihood of developing toxicity to Triomune.