Alexia Carmona

Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients

Objectives: To assess the effect of antiretroviral therapy (ART) adherence on survival in HIV‐infected patients. Design: Cohort study at a single hospital in Barcelona, Spain. Methods: Data on HIV‐infected patients older than 18 years of age who began ART during the period 1990 to 1999 were analyzed. Patients were considered nonadherent if the total dose of antiretroviral drug was less than 90% of that prescribed. Adherence was assessed through self‐report and hospital pharmacy appointments. Cox regression with time‐dependent variables was used. Results: A total of 1219 patients were included. The first ART was with monotherapy in 23.7% of cases, with two drugs in 30.5%, and with triple therapy in 45.8%. In multivariate analysis, the variables that presented significant differences with respect to mortality were clinical stage at the beginning of treatment (AIDS: relative hazard (RH) = 2.97; 95% confidence interval [CI]: 2.14‐4.13), CD4 cell count (<200 cells/&mgr;L: RH = 5.89; CI: 3.44‐10.10), type of treatment (monotherapy: RH = 9.76; CI: 4.56‐20.90; bi‐therapy: RH = 9.12; CI: 4.23‐19.64), and adherence (nonadherence: RH = 3.87; CI: 1.77‐8.46). Conclusions: The modifiable factors most strongly associated with survival were type of treatment and adherence. It would be desirable to accompany therapy with intervention strategies intended to improve adherence.

Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study

Objective To assess the effectiveness of the simplified medication adherence questionnaire (SMAQ) in identifying non-adherent patients. Design Prospective observational study of adherence. The six-item SMAQ was developed. The following aspects were evaluated: (i) criterion validity, comparison with electronic adherence monitoring; (ii) construct validity, association between adherence, as defined by the SMAQ, and virological outcomes; and (iii) reliability, internal consistency and reproducibility. Patients A group of 3004 unselected HIV patients who had initiated nelfinavir therapy combined with other antiretroviral drugs [21% naive, 15% protease inhibitor (PI)-naive, 64% PI-experienced] between January 1998 and December 1999 were enrolled in 69 hospitals in Spain. The SMAQ was administered at months 3, 6 and 12. Results The SMAQ showed 72% sensitivity, 91% specificity and a likelihood ratio of 7.94 to identified non-adherent patients, compared with the medication-event monitoring system (40 patients evaluated). At month 12, 1797 patients were evaluated, of whom 32.3% were defined as non-adherent; viral load < 500 copies/ml found in 68.3% of the adherent, and 46% of the non-adherent patients. A logistic regression analysis of PI-naive patients was performed, including age, sex, baseline viral load > 5 log10/ml, CD4 cell count < 200 × 106/l, and non-adherence as independent variables. Non-adherence was the only significant risk factor in failing to achieve virological suppression. Cronbachs alpha internal consistency coefficient was 0.75, and overall inter-observer agreement was 88.2%. Conclusion The SMAQ appears to be an adequate instrument with which to assess adherence in HIV-infected patients, and may be applied in most clinical settings.

Virologic Outcome and Predictors of Virologic Failure of Highly Active Antiretroviral Therapy Containing Protease Inhibitors

In this observational single-center cohort study outside the clinical trial setting, outcome and predictors of virologic failure of highly active antiretroviral therapy (HAART) containing a protease inhibitor were evaluated in human immunodeficiency (HIV)-infected persons. The study population consisted of 807 protease inhibitor-naive HIV-seropositive patients who initiated antiretroviral therapy with reverse transcriptase inhibitors and protease inhibitors (indinavir, nelfinavir, ritonavir) between January 1997 and January 1999. Demographic variable, plasma HIV-1 RNA levels, CD4+ T-cell count, adverse drug reactions, and adherence to HAART were assessed. Virologic treatment response was defined as a decrease in plasma HIV-1 RNA load from baseline to below 500 copies per milliliter after 12 months of therapy. Levels of HIV-1 RNA were undetectable in 43% of patients at 12 months. Factors associated with failure to suppress viral load included age 40 years or younger, baseline CD4+ T cell count less than 200 x 10(6) per liter baseline viral load greater than 4.3 log(10) per milliliter, and non-adherence to HAART. After adjustment by logistic regression, non-adherence was the only statistically significant variable associated with virologic failure (odds ratio 0.38, 95% confidence interval 0.21 to 0.67). Unselected patients in whom protease inhibitor is started in a usual clinical setting achieve viral suppression less frequently than do patients in controlled clinical trials. Failure to adherence to HAART was the strongest predictor of virologic failure.

Design of a score to identify hospitalized patients at risk of drug‐related problems

The potential impact of drug‐related problems (DRP) on morbidity and mortality is a serious concern in hospitalized patients. This study aimed to design a risk score to identify patients most at risk of a DRP.

Simplified Therapy with Zidovudine, Lamivudine, and Abacavir for Very Nonadherent, Treatment-Failing Patients

Abstract Objective: To assess the effectiveness of a simplified therapy for very nonadherent patients who had previously failed with HAART. Method: We performed a prospective open-label study of antiretroviral-experienced patients. Dosing schedule comprised (co-formulated) zidovudine, lamivudine, and abacavir bid. Eligible patients had to have plasma HIV RNA >5000 copies/mL, previous therapy, and very poor adherence to the medication regimen. Results: Eighty-five patients were included (mean viral load, 4.4 log/mL; mean CD4, 240 cells/mL; IDUs, 78%; methadone maintenance program, 42%; AIDS, 28%). Number of previous therapies: one, 53%; two, 28%; three or more, 19%. In the intent-to-treat analysis at 1 year, 38 patients (44.7%) achieved viral load below 500 copies/mL. Adherence greater than 90% of prescribed drugs was reported in 49% of patients, adverse events were reported in 17.6%, mortality in 6%, and lost to follow-up in 26%. The factors associated with virologic failure were nonadherence (odds ratio [OR], 4.4; 95% CI 1.5-12.3), baseline CD4 cell count <200 cells/mL (OR, 3.4; 95% CI 1.3-8.9; p = .01), and more than one previous treatment (OR, 2.7; 95% CI 1.1-6.9). Conclusion: Regarding previously very nonadherent patients, this simplified combination therapy containing three NRTIs obtained satisfactory results in ART-experienced patients. However, more aggressive interventions to enhance adherence are needed to improve results.