Cerebrospinal fluid HIV-1 RNA during treatment with ritonavir/saquinavir or ritonavir/saquinavir/stavudine

Objective: To assess the HIV-1-RNA response and drug concentrations in cerebro-spinal fluid (CSF) and serum during treatment with saquinavir (SQV)/ritonavir (RIV) or SQV/RIV plus stavudine (d4T) in HIV-1-infected patients. Design: A multicentre, open-label, randomized controlled trial. Methods: A total of 208 protease inhibitor (PI) and d4T-naive, HIV-1-infected patients were treated with RTV 400 mg twice daily and SQV 400 mg twice daily with or without d4T 40 mg twice daily. Intensification with reverse transcriptase inhibitors was allowed if serum HIV RNA remained above 400 copies/ml after 12 weeks. In 27 volunteers, CSF and serum HIV RNA were measured at baseline, weeks 12 and 48, using the Roche Amplicor and the ultrasensitive assay. In 22 patients, serum and CSF drug concentrations were determined at week 12. Results: The median baseline serum and CSF HIV-RNA concentrations were 4.81 and 3.21 log10 copies/ml, respectively. A difference in the proportion of patients with a CSF HIV-RNA level below the limit of quantification ( LLQ at week 12 in logistic regression analysis (P= 0.005). CSF RIV and SQV concentrations were < LLQ in most patients. Conclusion: RTV/SQV alone cannot suppress detectable CSF HIV-1-RNA levels to < LLQ after 12 weeks of treatment in the majority of patients. CSF drug concentrations of RTV and SQV < LLQ may explain the suboptimal antiretroviral effect in the CSF. (C) 2000 Lippincott Williams and Wilkins

Vie illustrée de Monseigneur de Ségur , par le Marquis de Ségur...

Background The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands. Materials and methods We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery. Results A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03−1.77, p = 0.03). The risk for SGA was highest in women who started a

Baseline characteristics of HIV-negative and HIV-positive women (by group–those starting cART prior to conception and those starting cART after conception).

<p>Baseline characteristics of HIV-negative and HIV-positive women (by group–those starting cART prior to conception and those starting cART after conception).</p

Neonatal outcomes stratified for PI- and NNRTI-based regimens and based on whether cART was started before or after conception.

<p>Neonatal outcomes stratified for PI- and NNRTI-based regimens and based on whether cART was started before or after conception.</p

Risk of babies being born SGA <10th percentile, by univariate and multivariate analysis, using a generalized estimation equation.

<p>Risk of babies being born SGA <10th percentile, by univariate and multivariate analysis, using a generalized estimation equation.</p

Outcome of HIV-exposed uninfected (HEU) singleton infants born to HIV-positive mothers by timing of initiation of cART—preconception vs postconception.

<p>Outcome of HIV-exposed uninfected (HEU) singleton infants born to HIV-positive mothers by timing of initiation of cART—preconception vs postconception.</p

Risk of a baby being born SGA <10th percentile.

<p>Multivariate analysis using a generalized estimation equation and stratified for PI- and NNRTI-based cART regimens.</p

High treatment uptake in human immunodeficiency virus/ hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands

Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa–based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients