title: Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study.
abstract: BACKGROUND
  The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain.
  
  
  OBJECTIVE
  The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study.
  
  
  METHODS
  Patients eligible for participation in the Recover Study are aged10 ≥18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ≥3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ≥6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003.
  
  
  RESULTS
  A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18-67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6-156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART regimens. The NRTIs with the highest discontinuation rates were stavudine (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI-related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550 cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170 [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine (70/77 cases [90.9%]).
  
  
  CONCLUSIONS
  The results of this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART.
authors.affiliation: Infectious Diseases Unit, Hospital Virgen de la Victoria, Málago, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Palacios
authors.affiliation: Infectious Diseases Unit, Hospital Virgen de la Victoria, Málago, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Santos
authors.affiliation: Deportment of Infectious Diseases, Donosti Hospital, Donosti, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Camino
authors.affiliation: Department of Infectious Diseases, Miguel Servet Hospital, Zaragoza, Spain.
authors.forename: Piedad
authors.initials: P
authors.lastname: Arazo
authors.affiliation: Department of Infectious Diseases, Severo Ochoa Hospital, Legonés, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Torres Perea
authors.affiliation: Department of Infectious Diseases, Marqués de Voldecilla University Hospital, Santander, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Echevarrfa
authors.affiliation: Department of Infectious Diseases, Vall d'Hebron Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Ribera
authors.affiliation: Medical Department, Gilead Sciences, Madrid, Spain.
authors.forename: Rainel
authors.initials: R
authors.lastname: Sánchez de la Rosa
authors.affiliation: Department of Infectious Diseases, Hospital Ramón y Cajol, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno Guillen
keywords: AIDS; HIV-1 infection; abacavir; didanosine; highly active antiretroviral therapy; lamivudine; nucleoside analogue reverse transcriptase inhibitor toxicity; stavudine; tenofovir; zidovudine