Cystatin C as a marker of renal function is affected by HIV replication leading to an underestimation of kidney function in HIV patients.

BACKGROUND: Broad use of tenofovir and an ageing HIV- infected population have created an interest in renal function in HIV patients. Serum cystatin C is a newer marker of renal function and might be more sensitive than creatinine. METHODS: Patients were enrolled consecutively in an observational study. HIV-seropositive patients naive to antiretroviral therapy (n = 261) were compared with healthy volunteers undergoing check-up procedures (n = 193). Estimated glomerular filtration rate (eGFR) was derived using creatinine-based Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formulas or cystatin C-based calculations. HIV-seropositive patients starting antiretroviral therapy (n = 92) were followed prospectively after enrolment. RESULTS: MDRD showed a higher median eGFR in antiretroviral-naive HIV-seropositive patients compared with controls (104 versus 93 ml/min; P < 0.001). Cockcroft-Gault gave similar results (118 versus 106 ml/min; P < 0.001). By contrast, cystatin C levels in HIV-seropositive individuals were higher, resulting in a lower median eGFR compared with controls (99 versus 120 ml/min; P < 0.001). Cystatin C was positively correlated with HIV RNA (r = 0.33, P < 0.01) and inversely correlated with CD4+ T-cell count (r = -0.29, P < 0.01). Initiating antiretroviral therapy (n = 92) decreased cystatin C levels and led to an increased cystatin C-based eGFR from median 84 to 103 ml/min at week 24 (P < 0.001). Serum creatinine was not substantially altered. CONCLUSIONS: Correlation of cystatin C with HIV RNA and CD4+ T-cell count, plus decrease of cystatin C after suppression of HIV replication, suggest an increase of cystatin C levels by active HIV infection. This might result in overestimation of renal impairment, particularly in treatment-naive patients. Therefore, use of cystatin C to calculate GFR in HIV-seropositive individuals should not be recommended without further validation.

Predictors of short-term success of antiretroviral therapy in HIV infection.

OBJECTIVES: The success of highly active antiretroviral therapy (HAART) in HIV infection may be influenced by numerous host factors. There is a lack of data presenting a combined assessment of a variety of these parameters for treatment efficacy in clinical routine practice. METHODS: Different indices of therapeutic drug monitoring (TDM) were evaluated prospectively in the context of self-reported adherence, health-related quality of life and social determinants, as measured by a questionnaire. RESULTS: A total of 210 individuals were studied between 2002 and 2004, 77% were males, mean age was 44 years, mean CD4 count was 336 cells/mm3 and 63% had a viral load < 50 copies/mL. In univariate analysis, baseline viral load, unscheduled drug levels, a 4 h pharmacokinetic profile (PK-P) at a scheduled visit and self-reported complete adherence within the previous 2 weeks were significantly associated with virological success of HAART at 12 weeks. At 24 weeks, only baseline viral load, the 4 h PK-P and adherence were significantly associated with HAART efficacy. In multivariate analysis, baseline viral load, adherence, unscheduled drug levels, trough levels at a visit with appointment as well as the 4 h PK-P were significantly associated with virological success at 12 weeks. At 24 weeks, only adherence was significantly linked to outcome. The other parameters were not found to have an impact on treatment efficacy. CONCLUSIONS: TDM and self-reported adherence were independently predictive of short-term HAART success in this prospective study. Unscheduled drug measurements provided similar diagnostic information as a 4 h PK-P. Thus, we propose the use of unscheduled drug level monitoring and self-reported adherence to help identify patients with elevated risk of virological failure.