title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Research Department, Infectious Diseases Institute, Makerere University, Kampala Uganda. bcastelnuovo@idi.co.ug
authors.forename: Barbara
authors.initials: B
authors.lastname: Castelnuovo
authors.forename: Agnes
authors.initials: A
authors.lastname: Kiragga
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Yukari
authors.initials: Y
authors.lastname: Manabe
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D015999:Multivariate Analysis; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D014454:Uganda / Q000453:epidemiology; D015215:Zidovudine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D018119:Stavudine; C098320:efavirenz