A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects

BackgroundThere has been major improvement in the survival of HIV-1 infected individuals since the South African Government introduced highly active anti-retroviral therapy (HAART) in the public sector in 2004. This has brought new challenges which include the effects of stavudine-related toxicities.MethodsProspective analysis of a cohort of 9040 HIV-infected adults who were initiated on HAART at the Themba Lethu Clinic (TLC) in Johannesburg between April 1, 2004 to December 31, 2007, and followed up until June 30, 2008.ResultsAmongst the 9040 study subjects, 8497(94%) were on stavudine based therapy and 5962 (66%) were women. The median baseline CD4 count was 81 cells/mm3 (IQR 29-149). Median follow up on HAART was 19 months (IQR: 9.1-31.6). The proportion of HAART-related side effects for stavudine compared to non-stavudine containing regimens were, respectively: peripheral neuropathy,17.1% vs. 11.2% (p < 0.001); symptomatic hyperlactataemia, 5.7% vs. 2.2% (p < 0.0005); lactic acidosis, 2.5 vs. 1.3% (p = 0.072); lipoatrophy, 7.3% vs. 4.6% (p < 0.05). Among those on stavudine-based regimens, incidence rates for peripheral neuropathy were 12.1 cases/100 person-years (95%CI 7.0-19.5), symptomatic hyperlactataemia 3.6 cases/100 person-years (95%CI 1.2-7.5), lactic acidosis 1.6 cases/100 person-years (95%CI 0.4-5.2) and lipoatrophy 4.6 cases/100 person-years (95%CI 2.1-9.6). Females experienced more toxicity when compared to males in terms of symptomatic hyperlactataemia (p < 0.0001), lactic acidosis (p < 0.0001), lipoatrophy (p < 0.0001) and hypertension (p < 0.05).ConclusionsWe demonstrate significant morbidity associated with stavudine. These data support the latest WHO guidelines, and provide additional evidence for other resource limited HAART rollout programs considering the implementation of non-stavudine based regimens as first line therapy.

• Publication year

  2011

• Venue

  BMC Infectious Diseases

• Publication date

  2011-09-17

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/1471-2334-11-244PMID 21923929PMCID 3189398
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• 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.

  2010cited by this paper
• Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

  2009cited by this paper
• Long term outcomes of antiretroviral therapy in a large HIV/AIDS care clinic in urban South Africa: a prospective cohort study

  2009cited by this paper
• Incidence and Risk Factors for New-Onset Diabetes in HIV-Infected Patients

  2008cited by this paper
• Metabolic Function and the Prevalence of Lipodystrophy in a Population of HIV-Infected African Subjects Receiving Highly Active Antiretroviral Therapy

  2007cited by this paper
• Use of antiretroviral therapy in resource-limited countries in 2006: distribution and uptake of first- and second-line regimens

  2007cited by this paper
• Higher-Than-Expected Rates of Lactic Acidosis Among Highly Active Antiretroviral Therapy-Treated Women in Botswana: Preliminary Results from a Large Randomized Clinical Trial

  2007influential reference
• Substitutions Due to Antiretroviral Toxicity or Contraindication in the First 3 years of Antiretroviral Therapy in a Large South African Cohort

  2007cited by this paper
• Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort.

  2007cited by this paper
• A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context.

  2006cited by this paper
• HIV/AIDS preventive vaccine ‘prime-boost’ phase III trial: foundations and initial lessons learned from Thailand

  2006cited by this paper
• Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.

  2006cited by this paper
• National adult antiretroviral therapy guidelines in resource-limited countries: concordance with 2003 WHO guidelines?

  2006cited by this paper
• Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa

  2004cited by this paper
• An objective case definition of lipodystrophy in HIV-infected adults: a case-control study.

  2003cited by this paper
• Outcome and predictors of failure of highly active antiretroviral therapy: one-year follow-up of a cohort of human immunodeficiency virus type 1-infected persons.

  1999cited by this paper
• Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.

  1998cited by this paper
• Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection.

  1998cited by this paper
• Decline in deaths from AIDS due to new antiretrovirals.

  1997cited by this paper

• A programmatic assessment of dolutegravir adverse events and discontinuations in Uganda

  2025cites this paper
• Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain

  2023cites this paper
• Global Prevalence of Chronic Pain in Women with HIV: A Systematic Review and Meta-analysis

  2023cites this paper
• Prevalence and incidence of hypertension in a heavily treatment-experienced cohort of people living with HIV in Uganda

  2023cites this paper
• Functioning Problems Associated with Health Conditions with Greatest Disease Burden in South Africa: A Scoping Review

  2022cites this paper
• Dyslipidemia and associated risk factors among HIV/AIDS patients on HAART in Asmara, Eritrea

  2022cites this paper
• Incidence and associated factors of type 2 diabetes mellitus onset in the Brazilian HIV/AIDS cohort study

  2021influential citation
• Neuroinflammation in HIV-Related Neuropathic Pain

  2021cites this paper
• Development of HIV drug resistance in a cohort of adults on first-line antiretroviral therapy in Tanzania during the stavudine era

  2020cites this paper
• HIV_A_275314 507..524

  2020influential citation
• Lipodystrophic syndrome of HIV and associated factors: a study in a university hospital.

  2020cites this paper
• Lipodystrophic syndrome of HIV and associated factors: a study in a university hospital

  2020cites this paper
• Conditional expression of HIV-1 Tat in the mouse alters the onset and progression of tonic, inflammatory, and neuropathic hypersensitivity in a sex-dependent manner.

  2020cites this paper
• Antiretroviral Therapy-Associated Metabolic Complications: Review of the Recent Studies

  2020cites this paper
• Epidemiology and factors associated with peripheral neuropathy among HIV infected patients in Gondar, Ethiopia: A cross-sectional study

  2019cites this paper
• Schistosomiasis and HIV-1 viral load in HIV-infected outpatients with immunological failure in Tanzania: a case-control study

  2019cites this paper
• Effective public-private partnerships for sustainable antiretroviral therapy: outcomes of the Right to Care health services GP down-referral program

  2019cites this paper
• Assessing treatment outcomes of people living with HIV on antiretroviral therapy at Kakamega County General Hospital in Kenya

  2019cites this paper
• Environmental fate and ecotoxicological effects of antiretrovirals: A current global status and future perspectives.

  2018cites this paper
• Anthropometric definitions for antiretroviral-associated lipodystrophy derived from a longitudinal South African cohort with serial dual-energy X-ray absorptiometry measurements

  2018cites this paper
• Pharmacogenetic variation influences sensory neuropathy occurrence in Southern Africans treated with stavudine-containing antiretroviral therapy

  2018cites this paper
• Sensitive detection of HIV-1 resistance to Zidovudine and impact on treatment outcomes in low- to middle-income countries

  2017cites this paper
• Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients

  2016cites this paper
• Stavudine-associated toxicity in patients on low-dose versus high-dose Stavudine in an HIV treatment cohort

  2016influential citation
• Metabolic complications resulting from the use of antiretroviral therapy in HIV-infected patients

  2016influential citation
• HIV and Statin Use in the Women's Interagency HIV Study

  2016influential citation
• Uptake of WHO Recommendations for First-Line Antiretroviral Therapy in Kenya, Uganda, and Zambia

  2015cites this paper
• Mechanisms involved in the accumulation of mitochrondrial DNA defects following anti-HIV therapy

  2015cites this paper
• Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study.

  2015cites this paper
• Changes in blood pressure, glucose levels, insulin secretion and anthropometry after long term exposure to antiretroviral therapy in South African women

  2015cites this paper
• Changing utilization of Stavudine (d4T) in HIV‐positive people in 2006–2013 in the EuroSIDA study

  2015cites this paper
• Predictors of Nonadherence to Antiretroviral Therapy among HIV-Infected Adults in Dar es Salaam, Tanzania

  2015cites this paper
• Peripheral Neuropathy in Children on Stauvudine Therapy

  2015cites this paper
• HIV/AIDS and lipodystrophy: Implications for clinical management in resource-limited settings

  2015influential citation
• Characteristics and Factors Associated with the Clinical Forms of Lipoatrophy during Highly Active Antiretroviral Therapy in Ouagadougou, Burkina Faso

  2014cites this paper
• Drug-induced peripheral neuropathy.

  2014cites this paper
• A randomized clinical trial comparing metabolic parameters after 48 weeks of standard‐ and low‐dose stavudine therapy and tenofovir disoproxil fumarate therapy in HIV‐infected South African patients

  2014cites this paper
• The development of simple anthropometric measures to diagnose antiretroviral therapy-associated lipodystrophy in resource limited settings

  2014cites this paper
• Factors associated with developing symptomatic HIV-associated sensory neuropathy

  2014cites this paper
• Hyperlactatemia in a group of HIV patients living in Yaounde-Cameroon

  2014influential citation
• Breast hypertrophy and gynaecomastia in HIV-associated lipodystrophy, a problematic side-effect of life-saving antiretroviral therapy

  2014cites this paper
• Monitoring the treatment and health of patients accessing HIV care in low and middle-income countries

  2014influential citation
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  2014cites this paper
• Simplification of Antiretroviral Therapy: A Necessary Step in the Public Health Response to HIV/AIDS in Resource-Limited Settings

  2014cites this paper
• Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial

  2014cites this paper
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  2014cites this paper
• Stavudine Induced Multiple Adverse Effects in HIV-Infected Patient

  2013cites this paper
• The nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors in the treatment of HIV infections (AIDS).

  2013cites this paper
• HIV-related neuropathy: current perspectives

  2013cites this paper
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  2013cites this paper
• Metabolic complications and treatment of perinatally HIV-infected children and adolescents

  2013cites this paper
• HIV-associated lipodystrophy in South Africa: the impact on the patient and the impact on the plastic surgeon.

  2013cites this paper
• Mitochondrial subhaplogroups and differential risk of stavudine-induced lipodystrophy in Malawian HIV/AIDS patients.

  2013cites this paper
• First-line antiretroviral therapy and changes in lipid levels over 3 years among HIV-infected adults in Tanzania.

  2013cites this paper
• [Pharmacosurveillance regarding Colombian patients being treated with stavudine].

  2013cites this paper
• Acute pancreatitis in HIV/AIDS patients: an issue of concern.

  2013cites this paper
• Stavudine dosage reduction : effect on symptomatic hyperlactataemia and lactic acidosis in patients at Dr George Mukhari Hospital, Pretoria : scientific letter

  2013cites this paper
• Investigation of lipodystrophy syndrome in a multicentre prospective cohort of HIV-infected children and adolescents living in Europe

  2013cites this paper
• Resultados de una intervencion de farmacovigilancia en pacientes con VIH/ SIDA tratados con estavudina Pharmacosurveillance regarding Colombian patients beingtreated with stavudine

  2013cites this paper
• The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV‐infected patients: a randomized trial

  2013cites this paper
• The effects of progressive resisted exerxcises on performance-oriented mobility in persons with HIV related poly-neuropathy

  2013cites this paper
• QUANTITATIVE ASSESSMENT OF THE PREVALENCE OF MITOCHONDRIAL TOXICITY IN HIV/AIDS PATIENTS INITIATED ON A STAVUDINE CONTAINING REGIMEN IN MOUNT AYLIFF HOSPITAL ARV CLINIC

  2013cites this paper
• The nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors in the treatment of HIV infections (AIDS).

  2013cites this paper
• Perinatally HIV‐Infected Adolescents

  2013cites this paper
• Painful HIV-associated sensory neuropathy.

  2012cites this paper
• HIV-1 Nef-Src Family Kinase Interaction: A Novel Target for the Inhibition of HIV-1 Pathogenesis

  2012cites this paper
• Why it’s time to say goodbye to stavudine ... everywhere

  2012cites this paper
• Stavudine induced lactic acidosis, risk factors and predictive laboratory markers : a nested case-control study in South Africa.

  2012cites this paper
• HIV in Africa: Challenges and Directions for the Next Decade

  2012cites this paper
• HIV-Associated Sensory Neuropathy: Risk Factors and Genetics

  2012influential citation
• HIV treatment and care in resource-constrained environments: challenges for the next decade

  2012cites this paper
• Prevalence of peripheral neuropathy in antiretroviral therapy naïve HIV-positive patients and the impact on treatment outcomes—a retrospective study from a large urban cohort in Johannesburg, South Africa

  2012cites this paper
• HIV-associated sensory neuropathy in HIV-1 infected patients at the Douala General Hospital in Cameroon: a cross-sectional study

  2012cites this paper
• Stavudine Toxicity in Adult Longer-Term ART Patients in Blantyre, Malawi

  2012cites this paper
• Women and HIV: motherhood and more

  2012cites this paper