Recombinant HIV-2 Tat Protein (D194)

International guidelines recommend the use of integrase strand transfer inhibitor (INI)-based regimens as first-line antiretroviral (ARV) in both naive and experienced HIV-infected patients. We analyzed a multicenter cohort of HIV-infected patients, both naive and experienced, starting an ARV, including an INI. Chi-square test and nonparametric tests were used to assess differences in categorical and continuous variables, respectively. Kaplan-Meier survival analysis was performed to estimate the probability of maintaining the study drug and Cox-regression analysis to evaluate predictors of discontinuation. We enrolled 4,343 patients: 3,143 (72.4%) were males, with a median age of 49 years (interquartile range 41-55). Naive patients were 733 (16.9%), of whom 168 (22.9%) were AIDS presenters. Overall, 2,282 patients (52.5%) started dolutegravir (DTG), 1,426 (32.8%) raltegravir (RAL), and 635 (14.7%) elvitegravir (EVG). During 10,032 patient years of follow-up (PYFU), we observed 1,278 discontinuations (13 per 100 PYFU); 448 of them (35%) due to simplification and 355 (28%) to toxicities (98 for central nervous system toxicity). Reasons of discontinuation were different between INIs. Estimated probability of maintaining DTG at 3 and 4 years were 81.5% [95% confidence interval (CI): 80.5-82.5] and 76.3% (95% CI: 73.9-78.7), respectively; RAL 61.6% (95% CI: 60.2-63.0) and 54.1% (95% CI: 52.7-55.5); EVG 71.6% (95% CI: 69.2-74.0) and 68.3% (95% CI: 65.3-71.3) (p < .001). At a multivariable analysis, being on a RAL-based ARV [vs. DTG, adjusted hazard ratio (aHR) 2.9, 95% CI: 2.3-3.6, p < .001], a EVG-based ARV (vs. DTG, aHR 1.3 95% CI: 1.1-1.7, p = .049), and a peak HIV-RNA >500k cp/mL (aHR 1.3, 95% CI: 1.1-1.6, p = .006) predicted INI discontinuation. Our data confirm the good tolerability of INIs in clinical practice. Differences emerge between the three drugs in reasons for discontinuation.

Background: Reliable estimates of glomerular filtration rate (GFR) are important in the clinical management of HIV-positive patients. Data on the performance of widely used estimating equations (eGFR) relative to exogenously measured GFR are sparse in this population. Methods: We evaluated cross-sectional and longitudinal accuracy and bias of eGFR, based on creatinine and cystatin C, relative to disappearance of infused iohexol from plasma (iGFR) in a cohort of participants followed annually for up to 7 years. Results: A total of 222 HIV-positive and 139 HIV-negative participants contributed 1240 visits with valid iGFR and eGFR measures. Estimated GFR based on both creatinine and cystatin C performed the best. Estimated GFR based on creatinine alone overestimated iGFR by 9 mL center dot min center dot 1.73 m(-2) on average and was significantly less accurate in HIV-positive than HIV-negative individuals. The performance of equations based on either creatinine alone or cystatin C alone were significantly affected by participant factors (eg, non-suppressed HIV RNA, nadir CD4 count, hepatitis C virus coinfection). The average iGFR slope was -4% per year in HIV-positive participants. In both HIV-positive and HIV-negative participants, eGFR slope measures were generally unbiased but inaccurate, with only 60%-74% of observations falling within +/- 5% points of iGFR slope. Conclusions: Both creatinine and cystatin C have limitations as GFR indices in HIV-positive individuals. Estimated GFR based on both creatinine and cystatin C performed best in our study and may be preferred in HIV-positive persons with kidney disease or comorbidities that place them at high risk for kidney disease.