Exposure to dolutegravir in pregnant women living with HIV in Central and Eastern Europe and neighboring countries — data from the ECEE Network Group

Objectives: The purpose of this study was to investigate dolutegravir (DTG) use among women and exposure to DTG during pregnancy in real world in Central and Eastern Europe and neighboring countries. Material and methods: Centres from 20 countries included in the Euroguidelines in Central and Eastern Europe (ECEE) Network and Finland were asked to complete an on-line questionnaire. Results: Seven centres from Czech Republic, Finland, Greece, Poland, Slovakia, and Turkey provided detailed information. DTG exposure was reported in 415 women, of which 26 were during pregnancy. Of those, 22 were on DTG at the time of conception and 4 had started DTG during pregnancy. Few women had conventional risk factors. The data on folic acid usage was unknown for eight women; 14 were using and four were not using folic acid. Four pregnancies were ongoing at the time of the study and of those with an outcome, 77.3% resulted with term, 13.6% preterm delivery, 4.5% spontaneous and 4.5% medical abortion. Conclusions: The DTG signal report indicates the importance of safety research for drug use in pregnancy and highlights the urgent need for systematic surveillance of pregnancy outcomes and neonatal surveillance. Countries with low- or moderate HIV prevalence should be included in studies reviewing pregnancy outcomes and in any surveillance system to ensure the accuracy of drug safety revision

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are 500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Risk Factors for Low CD4+ Count Recovery Despite Viral Suppression among Participants Initiating Antiretroviral Treatment with CD4+ Counts > 500 cells/mm3: Findings from the Strategic Timing of AntiRetroviral Treatment (START) Trial.

BACKGROUND Low CD4+ recovery among HIV-positive individuals who achieve virologic suppression is common but has not been studied among individuals initiating treatment at CD4+ counts > 500 cells/mm. SETTING United States, Africa, Asia, Europe & Israel, Australia, Latin America. METHODS Among immediate-ART participants in the Strategic Timing of AntiRetroviral Therapy trial, low CD4+ recovery was defined as a CD4+ increase < 50 cells/mm from baseline after 8 months despite viral load ≤ 200 copies/mL. Risk factors for low recovery were investigated with logistic regression. RESULTS 39.7% of participants had low CD4+ recovery. Male gender (OR 1.53, p = 0.007), lower screening CD4+ (OR 1.09 per 100 fewer cells/mm, p = 0.004), higher baseline CD8+ (OR 1.05 per 100 more cells/mm, p < 0.001), and lower HIV RNA (OR 1.93 per log10 decrease, p < 0.001) were associated with low CD4+ recovery. D-dimer had a quadratic association with low CD4+ recovery, with lowest odds occurring at 0.32 μg/mL. At lower HIV RNA levels, odds of low recovery were elevated across levels of screening CD4+ count, but at higher levels, odds of low CD4+ recovery were greater among those with lower versus higher screening CD4+. CONCLUSION Low CD4+ recovery is frequent among participants starting ART at high CD4+ counts. Risk factors include male gender, lower screening CD4+ cell counts, higher CD8+ cell counts, and lower HIV RNA levels. More follow-up is required to determine the impact of low CD4+ recovery on clinical outcomes

Chronic Kidney Disease and Exposure to ART in a large cohort with Long-term Follow-up: The EuroSIDA study

For the EuroSIDA study Groupinfo:eu-repo/semantics/nonPublishe

Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

OBJECTIVES: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. DESIGN: A cohort study including 6843 HIV-positive persons with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. METHODS: CKD was defined as either confirmed (two measurements >or=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above 60 ml/min per 1.73 m or confirmed 25% decline in eGFR for persons with baseline eGFR of 60 ml/min per 1.73 m or less, using the Cockcroft-Gault formula. Poisson regression was used to determine factors associated with CKD. RESULTS: Two hundred and twenty-five (3.3%) persons progressed to CKD during 21 482 person-years follow-up, an incidence of 1.05 per 100 person-years follow-up [95% confidence interval (CI) 0.91-1.18]; median follow-up was 3.7 years (interquartile range 2.8-5.7). After adjustment for traditional factors associated with CKD and other confounding variables, increasing cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06-1.25, P < 0.0001), indinavir (IRR 1.12, 95% CI 1.06-1.18, P < 0.0001), atazanavir (IRR 1.21, 95% CI 1.09-1.34, P = 0.0003) and lopinavir/r (IRR 1.08, 95% CI 1.01-1.16, P = 0.030) were associated with a significantly increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral drugs were associated with increased incidence of CKD. CONCLUSION: In this nonrandomized large cohort, increasing exposure to tenofovir was associated with a higher incidence of CKD, as was true for indinavir and atazanavir, whereas the results for lopinavir/r were less clear

Plasma HIV-1 Tropism and the Risk of Short- Term Clinical Progression to AIDS or Death

Objective To investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management. Design Nested case-control study within the EuroSIDA cohort. Methods Cases were subjects with AIDS or who died from any cause, with a plasma sample with HIV-1 RNA >1000 copies/mL available for tropism testing 3 to 12 months prior to the event. At least 1 control matched for age, HIV-1 RNA and HCV status at the time of sampling were selected per each case. Conditional logistic regression was used to investigate exposures associated with clinical progression to AIDS or death. A linear mixed model with random intercept was used to compare CD4+T-cell slopes by HIV tropism over the 12 months following the date of sampling. Results The study included 266 subjects, 100 cases and 166 controls; one quarter had X4 HIV; 26% were ART-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0.022) and calendar year of sample [OR = 0.84 (95CI = 0.77, 0.91) per more recent year, p<0.001). Baseline tropism was not associated with the risk of clinical progression or death. CD4+T-cell slopes did not differ within or between tropism groups