Article

Cingolani A, Antinori A, Rizzo MG, et al.. Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study (ARGENTA)

Istituto di Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy.
AIDS (Impact Factor: 6.56). 03/2002; 16(3):369-79. DOI: 10.1097/00002030-200202150-00008
Source: PubMed

ABSTRACT 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.
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.
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.
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/microl 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.
The virological benefit of genotype-guided treatment decisions in heavily pre-exposed patients was short term. Patients adherence and residual treatment options influenced outcomes.

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    • "Taking into account antiviral drug resistance, when choosing a therapy, is included in international guidelines (Vandamme et al., 2004; Yeni et al., 2004). Although both resistance phenotyping and genotyping after treatment failure have proven to be predictive for the next therapy response (Cingolani et al., 2002; Cohen et al., 2002; Mazzotta et al., 2003; Meynard et al., 2002; Perez-Elias et al., 2003; Tural et al., 2002; Wegner et al., 2004), genotyping is the preferred test for the routine follow-up of patients because of its faster turn-around time, the less complicated technique, and its lower cost (300–500D versus 800–1000D ). So far, no controlled prospective clinical studies have shown the advantage of using resistance testing in untreated patients although many retrospective studies support resistance testing also in drug naives (Little et al., 2002; Novak et al., 2005) such that guidelines also include resistance testing in particular circumstances for the first regimen. "
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    • "However, even though an exhaustive IAS mutation list is accessible to clinicians and many free-of-charge websites [Beerenwinkel et al., 2003; Kuiken et al., 2003; Rhee et al., 2003] furnish a computer-assisted interpretation of mutational profiles, some discrepancies continue to exist between these resistance profiles and response to therapy [Kijak et al., 2003; Ravela et al., 2003; Sturmer et al., 2003; Torti et al., 2003; De Luca et al., 2004]. Although good compliance with treatment regimens [Paterson et al., 2000; Cingolani et al., 2002], optimal antiviral potency [Daar, 2003; Gathe, 2003], "
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