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)
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.
- SourceAvailable from: Jurgen Vercauteren
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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. "
ABSTRACT: Drug resistance testing has proven its use to guide treatment decisions in HIV-1 infected patients. Genotyping is the preferred technique for clinical drug resistance testing. Many factors complicate the interpretation of mutations towards therapy response, such that an interpretation system is necessary to help the clinical virologist. No consensus interpretation exists to date and experts often have quite different opinions. As a result, several algorithms for the interpretation of HIV-1 genotypic drug resistance information have been designed. Clinical evaluation of their genotypic interpretation is not always straightforward. We describe a few publicly available systems and their clinical evaluation. We also stress that in addition to drug resistance, for effective management of HIV infection the clinician needs to take into account all potential causes of treatment failure. Successful therapy heavily relies on the expertise of the clinician.Antiviral Research 10/2006; 71(2-3):335-42. DOI:10.1016/j.antiviral.2006.05.003 · 3.94 Impact Factor
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- "The success of HAART is dependent upon close adherence to prescribed medication regimens (Carpenter et al., 1997; Hogg et al., 1998; Mocroft et al., 1998; Palella et al., 1998). When adherence is optimal, there is a high likelihood of virologic and immunologic success, and less likelihood of spread of drug resistant virus (Bangsberg et al., 2000; Cingolani et al., 2002; Little, 2001; Paterson et al., 2000). However, in resource-rich countries, the benefits of successful HIV therapy have not been realized by all persons living with HIV/AIDS (Anderson & Mitchell, 2000; Bozzette et al., 2001; Cunningham et al., 1999; Hader et al., 2001; Shapiro et al., 1999). "
ABSTRACT: Sustained virological suppression requires adherence to >95% of doses of therapy. Overall there is paucity of data on adherence interventions among women and post-intervention outcomes. In this pilot study, we evaluated a novel strategy of weekly delivery of medications (Directly Delivered Therapy: DDT) for six months using an outreach worker (ORW), among ARV naïve indigent women starting HAART and compared the 'during intervention' and 'post-intervention' outcomes to the health care team (a nurse educator, a case worker, a pharmacist and social worker/drug addictions counsellor) based approach termed Adherence Coordination Services (ACS) and the Standard of Care (SoC) historical referent group. The baseline characteristics of the three groups were comparable. The proportion of women who achieved sustained virologic suppression in 4-8 month period for DDT; ACS and SoC groups were 86% (18/21); 54% (6/11); and 36% (8/22) (P<0.004); and in the 10-14 month period were 80% (12/15); 54% (6/11) and 45%(10/22) (P=0.036 for DDT vs. SoC). Retention rate in the DDT was 87%, and 92% of 307 ORW visits were kept, and post-intervention satisfaction was high. Short-term weekly delivery of medications using a community based liaison is a feasible, acceptable and a cost-effective strategy for improving both short-term and perhaps long-term adherence among women initiating their first HAART regimen.AIDS Care 06/2006; 18(4):332-8. DOI:10.1080/09540120500162155 · 1.60 Impact Factor
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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], "
ABSTRACT: An extended spectrum of HIV-1 reverse-transcriptase (RT) mutations in HAART-treated patients has been recently described. To verify the possible association of previously unreported RT mutations with a decrease of phenotypic susceptibility to nucleoside (NRTIs) and non-nucleoside (NNRTIs) RT inhibitors, the RT sequence of 328 HIV-1-positive patients (102 naïve and 226 treated with HAART participating in either the PhenGen or Genpherex study) was analyzed. All treated patients were tested at the time of therapeutic failure with both phenotypic (Antivirogram, Virco) and genotypic analyses (VircoGen); the frequency of RT substitutions (positions 1-240) with respect to consensus B was compared to that of naïve patients using a Chi-square test. Amino acid changes at 13 positions not included in the IAS list of resistance-associated mutations were detected more frequently in treated than in naïve subjects. The mutations involving 10 of these positions were associated with a reduced susceptibility to antiretroviral drugs; K20R, T39A, K43EQN, E203KD, H208Y, and D218E were correlated with NRTI resistance while mutations K101EQP, H221Y, K223EQ, L228HR were associated to NNRTI resistance. A correlation was found between K20R and lamivudine resistance (P = 0.006) while T39A (P = 0.005), K43EQN (<0.001), E203KD (P = 0.010), and H208Y (P = < 0.001) seemed to be associated with a previous use of zidovudine and stavudine and with the development of thymidine analog resistance. For H208Y, an association with use/resistance to abacavir (P = 0.004) was also noted. D218E showed a weak association to didanosine resistance (P = 0.013). The data confirm that previously unreported mutations are associated with antiretroviral drug experience and, more importantly, with a reduced susceptibility to NRTIs and NNRTIs.Journal of Medical Virology 01/2006; 78(1):9-17. DOI:10.1002/jmv.20500 · 2.22 Impact Factor