Stavudine toxicity in women is the main reason for treatment change in a 3-year prospective cohort of adult patients started on first-line antiretroviral treatment in Uganda

J Acquir Immune Defic Syndr. 2011 Jan 1;56(1):59-63. doi: 10.1097/QAI.0b013e3181f5bd03.

Abstract

Purpose: In resource-limited settings, there are only a few antiretroviral treatment (ART) options. Our objective was to evaluate the reasons for first-line ART changes in resource-limited settings.

Methods: Prospective research cohort of patients initiating ART between April 2004 and April 2005 in Kampala, Uganda. The main endpoint was the substitution of at least 1 drug included in the initial combination.

Results: Five hundred Fifty-nine patients initiated on ART, 70% were female, median CD4+ count 98 (21-163) cells per microliter, median HIV RNA log₁₀ 5.4 (5.0-5.8). 413 (74%) patients were started on stavudine, lamivudine, and nevirapine, and 146 (36%) on zidovudine, lamivudine and efavirenz. One hundred Forty-eight (26.5%) had at least one treatment change (incidence rate 14.3 per 100 person-years; confidence interval: 12.2 to 16.9). The main reason for first treatment change was drug toxicity (n = 91, 61.5%). Stavudine accounted for the majority of the toxicities that led to drug substitution (n = 76, 84%). In the multivariate analysis, being female (P = 0.011) and being stage 3-4 as compared with 1-2 at ART initiation were predictive of stavudine substitution (P = 0.05). There was no difference in virologic outcome in patients who changed due to toxicity compared with those who did not.

Conclusions: The majority of the treatment changes were due to stavudine-related toxicity. Long-term stavudine use is less well tolerated in women.

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Benzoxazines / administration & dosage
  • Benzoxazines / therapeutic use
  • Cyclopropanes
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Lamivudine / administration & dosage
  • Lamivudine / therapeutic use
  • Male
  • Multivariate Analysis
  • Nevirapine / administration & dosage
  • Nevirapine / therapeutic use
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Stavudine / administration & dosage
  • Stavudine / adverse effects*
  • Stavudine / therapeutic use
  • Uganda / epidemiology
  • Zidovudine / administration & dosage
  • Zidovudine / therapeutic use

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Lamivudine
  • Zidovudine
  • Nevirapine
  • Stavudine
  • efavirenz