Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda (original) (raw)
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Management of antiretroviral drug toxicity
Current Opinion in HIV and AIDS, 2006
Purpose of review With the emergence of very potent antiretroviral regimens, the major limitation to the success of treatment is now the tolerability of drugs, which can ultimately affect adherence. It is important, therefore, to review the current understanding on antiretroviral drug toxicity, and examine key recent data that can inform the successful avoidance or management of such toxicities. Recent findings A common theme of recent research has focussed on the genetic predisposition to important immediate side-effects, such as abacavir hypersensitivity, nevirapine hepatotoxicity, efavirenz neurotoxicity and hyperbilirubinemia with atazanavir. Long-term toxicities such as body-composition changes and hyperlipidemia have been more closely linked to thymidine analogues and certain protease inhibitors. The management of these toxicities has also been clarified by studies addressing switching antiretroviral drugs or specific treatments for metabolic syndromes. Summary Recent data emphasize the need for the prevention of antiretroviral toxicity by the avoidance of some drugs in certain genetically predisposed populations or by the avoidance of entire classes if possible. In addition, recent studies emphasize the importance of ongoing research to determine the emergence of additional toxicities, as new drugs emerge and achieve widespread use.
Stavudine Toxicity in Adult Longer-Term ART Patients in Blantyre, Malawi
PLoS ONE, 2012
Background: Stavudine is an effective and inexpensive antiretroviral drug, but no longer recommended by WHO for firstline antiretroviral regimens in resource-limited settings due to toxicity concerns. Because of the high cost of alternative drugs, it has not been feasible to replace stavudine in most adults in the Malawi ART programme. We aimed to provide policy makers with a detailed picture of stavudine toxicities in Malawians on longer-term ART, in order to facilitate prioritization of stavudine replacement among other measures to improve the quality of ART programmes. Methods: Prospective cohort of Malawian adults who had just completed one year of stavudine containing ART in an urban clinic, studying peripheral neuropathy, lipodystrophy, diabetes mellitus, high lactate syndromes, pancreatitis and dyslipidemia during 12 months follow up. Stavudine dosage was 30 mg irrespective of weight. Cox regression was used to determine associations with incident toxicities. Results: 253 patients were enrolled, median age 36 years, 62.5% females. Prevalence rates (95%-confidence interval) of toxicities after one year on stavudine were: peripheral neuropathy 21.3% (16.5-26.9), lipodystrophy 14.7% (2.4-8.1), high lactate syndromes 0.0% (0-1.4), diabetes mellitus 0.8% (0-2.8), pancreatitis 0.0% (0-1.5). Incidence rates per 100 personyears (95%-confidence interval) during the second year on stavudine were: peripheral neuropathy 19.8 (14.3-26.6), lipodystrophy 11.4 (7.5-16.3), high lactate syndromes 2.1 (0.7-4.9), diabetes mellitus 0.4 (0.0-1.4), pancreatitis 0.0 (0.0-0.2). Prevalence of hypercholesterolemia and hypertriglyceridemia increased from 12.1% to 21.1% and from 29.5% to 37.6% respectively between 12 and 24 months. 5.5% stopped stavudine, 1.3% died and 4.0% defaulted during follow up. Higher age was an independent risk factor for incident peripheral neuropathy and lipodystrophy. Conclusion: Stavudine associated toxicities continued to accumulate during the second year of ART, especially peripheral neuropathy and lipodystrophy and more so at increasing age. Our findings support investments for replacing stavudine in first-line regimens in sub-Saharan Africa.
Journal of the International Association of Physicians in AIDS Care, 2007
Background: Generic, low-cost, nevirapine (NVP)-based antiretroviral therapy (ART) has improved survival in HIV-infected individuals living in resource-limited settings. However, there is concern about the potential hepatotoxicity of these regimens. Methods: The authors conducted a prospective study of persons initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. Results: The 97 study participants were predominantly women (64%), median age was 35 (interquartile range [IQR] 30-40), median CD4 at baseline was 56 cells/mm3 (IQR 8-138), and 19% had lifetime alcohol problems (CAGE ≥ 2). Severe liver enzyme elevations (LEEs) of grade 3-4 were rare (2.2%); however, 1 patient died in the setting of grade 4 LEEs. Grade 1-4 LEEs occurred among 22.2% of participants, and 9.8% had new grade 1-4 LEEs after the initiation of treatment. Discussion: The authors found that LEEs were common but that severe hepatotoxicity in persons initiating NVP-based ART was infrequent yet potentially...
Adverse Effect Profile of Antiretroviral Drugs in the Initial Three Months of Therapy
2018
BACKGROUND HIV disease is becoming increasingly prevalent. With ART being available in government ART centres and also drugs prices getting cheaper, most HIV patients receive ART. Success of ART treatment depends on patient compliance and major factor interfering with compliance is drugs toxicities. Adverse effects often trivial earlier are the major cause of patient drop out. Hence, we studied ART toxicity in first 3 months of therapy. MATERIALS AND METHODS Ninety-three successive patients started on ART in our institutional ART centre were enrolled for this study. Base line parameters including clinical status, CD4 count and baseline investigation were done as per NACO guidelines. (1,4). They were followed for three months for clinical and lab evidence of toxicity. Laboratory monitoring was done as per NACO recommendations. The impact of toxicity on treatment interruptions were documented and analysed. RESULTS Following common early toxicity was observed in this study: anorexia and vomiting occurred in 44% (N 24 + 17 pts) fatigue and anaemia in 26% (24 pts) pruritus and rash in 10% (9 pts). 6% patient had psychiatric manifestation and 7% (6 pts) had ALT elevation however hepatotoxicity was not found to be a major problem despite many patients being on ART and ATT simultaneously. None of the patients with gastro-intestinal symptoms, psychiatric manifestation and ALT elevation needed change in ART due to toxicities. 5 of 9 (56%) patients who had skin reactions and 10 of 24 (42%) patients who had developed anaemia had to change their initial ART regimen. Stavudine for zidovudine in patients associated with anaemia and Nevirapine to Efavirenz in patients with skin reactions. Minimal number of patients stopped their treatment for 1-2 weeks for rash, vomiting etc., underscoring the importance of this minor symptoms in patient compliance. Age, gender, baseline CD4 count and concurrent ATT were not predictors of toxicity in our study, zidovudine was found to be significantly associated with occurrence of anaemia and Nevirapine with skin toxicity. CONCLUSION In this study of 93 HIV positive patients newly started on ART, the early toxicities observed were anorexia and vomiting, fatigue and anaemia, pruritus and skin rash, psychiatric manifestations and ALT elevations.