Stavudine Toxicity in Adult Longer-Term ART Patients in Blantyre, Malawi

Abstract

BackgroundStavudine is an effective and inexpensive antiretroviral drug, but no longer recommended by WHO for first-line 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.MethodsProspective 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.Results253 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 person-years (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.ConclusionStavudine 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.

Comparison of Zidovudine Combination and Tenofovir Combination on the Effectiveness of Therapy and Side Effects in Hiv/Aids Patients in Rsal Mintohardjo

“…Patients using a combination of zidovudine in this study of patients were anemic when using zidovudine-containing therapy, and as many as 15% of the patients had to substitute therapy due to severe anemia. The results of this study were in line with the results of a study conducted by Parkes-Ratanshi et al (2016) that showed the risk of anemia in patients taking zidovudine was 2.7 times greater than that of patients taking a tenofovir combination [5].…”

“…Stavudine was replaced by tenofovir, which was formerly a second-line therapy [5]. Tenofovir has shown fewer side effects compared to either stavudine or zidovudine [6].…”

Profile of serious adverse drug events in a tertiary care hospital of South India - a five years experience

“…35 Pancreatitis has been predominantly associated with the usage of nucleoside reverse transcriptase inhibitors (NRTIs) such as didanosine and stavudine. 36 Being used widely and frequently, NSAIDs are often associated with ADEs. 37 The main safety concerns while using NSAIDs are gastrointestinal, renal, cardiovascular, hematologic effects, hepatic and allergic reactions.…”

Acute Pancreatitis in Patients Living with HIV

“…It represents a management problem because of its diverse modes of expression, multiplicity of causes and the high mortality rate. [4] Historically, this has been predominantly associated with the usage of nucleoside reverse transcriptase inhibitors (NRTIs) such as didanosine and stavudine [5,6], release of opportunistic agents (cytomegalovirus, cryptosporidiosis, Mycobacterium tuberculosis) or Kaposi disease. The advent of protease inhibitors in the late 1990s enabled a clear regression of incidence of these diseases [7].…”