Objective: To establish the influence of genotypic resistance-guided treatment decisions and patient-reported adherence on the virological and immunological responses in patients failing a potent antiretroviral regimen in a randomized, controlled trial in a tertiary care infectious diseases department.
Patients: A total of 174 patients with virological failure were randomly assigned to receive standard of care (SOC) or additional genotypic resistance information (G). Adherence was measured by a self-administered questionnaire.
Main outcomes measures: Primary endpoints were the proportion with HIV-RNA < 500 copies/ml at 3 and 6 months by intention-to-treat analysis. Secondary endpoints were changes from baseline HIV-RNA levels and CD4 cell counts.
Results: At entry, 25% had failed three or more highly active antiretroviral therapy (HAART) regimens and 41% three drug classes; there were more resistance mutations in G. In 127 evaluable questionnaires, 43% reported last missed dose during the previous week. At 3 months, 11 of 89 patients (12%) in SOC and 23 of 85 (27%) in G had HIV-RNA < 500 copies/ml (OR 2.63, 95% CI 1.12–6.26); the relative proportions were 17 and 21% at 6 months. CD4 cell changes did not differ between arms. Six month CD4 cell changes were +62 in adherent and −13 cells/μl in non-adherent patients (P < 0.01). Being assigned to G, good adherence, previous history of virological success, fewer experienced HAART regimens and lower baseline viral load were independently predictive of 3 month virological success.
Conclusion: The virological benefit of genotype-guided treatment decisions in heavily pre-exposed patients was short term. Patients adherence and residual treatment options influenced outcomes.
From the aIstituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy; and bIstituto Nazionale per le Malattie Infettive ‘Lazzaro Spallanzani', IRCCS, Rome, Italy.
Requests for reprints and correspondence to: Andrea De Luca, MD, Istituto di Clinica delle Malattie Infettive, Università Cattolica del S. Cuore, Largo Agostino Gemelli, 8 – 00168 Rome, Italy. Tel: +39 06 3015 4945; fax: +39 06 3054 519; e-mail: email@example.com
Received: 18 May 2001;
revised: 17 September 2001; accepted: 19 September 2001.
Sponsorship: This work was supported by Programma Nazionale di Ricerca sull'AIDS, Istituto Superiore di Sanità, Progetto Patologia, Clinica e Terapia and by Ricerca Corrente e Finalizzata degli IRCCS, Ministero della Sanità, Italy.