Risk factors for urological symptoms in a cohort of users of the HIV protease inhibitor indinavir sulfate: The ATHENA cohort

Background: Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency. Objective: To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use. Methods: This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996. Results: The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7;95% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2;95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4;95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1;95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9;95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass. Conclusion: Increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environments

Limited patient adherence to highly active antiretroviral therapy for HIV-1 infection in an observational cohort study

Background: Adherence to highly active antiretroviral therapy (HAART) for human immunodeficiency syndrome type 1 (HIV-1) infection is essential to sustain viral suppression and prevent drug resistance. We investigated adherence to HAART among patients in a clinical cohort study. Methods: Patients receiving HAART had their plasma concentrations of protease inhibitors or nevirapine measured and completed a questionnaire on adherence. We determined the percentage of patients who reported taking all antiretroviral medication on time and according to dietary instructions in the past week. Drug exposure was compared between patients reporting deviation from their regimen and fully adherent patients. Among patients who received HAART for at least 24 weeks, we assessed the association between adherence and virologic outcome. Results: A total of 224 of 261 eligible patients completed a questionnaire. Forty-seven percent reported taking all antiretroviral medication on time and according to dietary instructions. Patients who reported deviation from their regimen showed lower drug exposure compared with fully adherent patients (median concentration ratio, 0.81 vs 1.07; P=.001). Among those receiving HAART for at least 24 weeks, patients reporting deviation from their regimen were less likely to have plasma HIV-1 RNA levels below 500 copies/mI. (adjusted odds ratio, 4.0; 95% confidence interval, 1.4-11.6) compared with fully adherent patients. Conclusions: Only half of the patients took all antiretroviral medication in accordance with time and dietary instructions in the preceding week. Deviation from the antiretroviral regimen was associated with decreased drug exposure and a decreased likelihood of having suppressed plasma HIV-1 RNA loads. Patient adherence should remain a prime concern in the management of HIV-1 infection