Evolution of renal function in African patients initiating second-line antiretroviral treatment : findings from the ANRS 12169 2LADY trial

Background: To investigate change in renal function in African patients initiating second-line antiretroviral therapy (ART) including ritonavir-boosted protease inhibitor (PI/r) with or without tenofovir disoproxil fumarate (TDF). Methods: HIV-1-positive adults, failing standard first-line ART were randomized to either TDF/emtricitabine (FTC)+LPV/r, abacavir + didanosine +LPV/r or TDF/FTC+darunavir (DRV)/r and followed for 18 months. Patients with an estimated glomerular filtration rate (eGFR) >= 60 ml/min/1.73 m(2) at baseline were included in this analysis. Results: Data from 438 out of 454 randomized patients were analysed. Median age was 38 years and 72% were women. Initiation of PI/r-based second-line regimen induced a marked eGFR decline of -10.5 ml/min/1.73 m2 at week 4 in all treatment groups with a greater decrease in TDF/FTC+LPV/r arm (-15.1 ml/min/1.73 m(2)). At month 18, mean eGFR in the non-TDF containing regimen recovered its baseline level and was significantly greater than eGFR 18-month levels in the TDF-containing regimens that experienced only partial recovery (difference: -10.7; CI -16.8, -4.6; P=0.001 in TDF/FTC+LPV/r and -6.4; CI -12.5, -0.3; P=0.04 in TDF/FTC+DRV/r). At 18 months, prevalence of stage 3 chronic kidney disease was low (60 ml/ml/1.73 m(2) at baseline. They also support the recommendation of reassessing renal function 1 month after initiation of treatment including ritonavir to account for the ritonavir-related artefactual decrease of eGFR and determine the new reference baseline value

Etiology of the portal hypertension syndrome in the tropics

Le syndrome d'hypertension portale (HTP) est fréquemment rencontré dans les services de Médecine à Bamako. Cependant, aucune étude au Mali ne lui a été consacrée ; d'où l'intérêt de notre étude dont l'objectif était de déterminer la fréquence de l'HTP et ses différentes étiologies. Nous avons réalisé une étude rétrospective allant de janvier 1990 à décembre 1998 et prospective de janvier à décembre 1999. Les malades ayant une HTP et ayant eu une biopsie hépatique ont été inclus. Les dossiers ne comportant pas de résultats de l'examen anatomopathologique n'ont pas été inclus. Les fragments biopsiques ont été prélevés avec une pince à biopsie au cours de la laparoscopie ou par la ponction biopsie hépatique (PBH) à l'aiguille de Menghini. 206 malades répondaient aux critères d'inclusion : 132 hommes et 74 femmes. L'âge moyen était de 43,2 +/-15 ans avec des extrêmes à 8 et 80 ans. La fréquence de l'HTP a été de 10,9 % (524/4858). Les étiologies ont été dominées par la cirrhose : 43,2 % (89/206), le cancer primitif du foie : 18,4 % (38/206) et l'hépatite chronique : 14,5 % (30/206). La bilharziose hépatique a été une étiologie rare dans notre série : 3,4 %

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP) : a multicentre, randomised, parallel, open-label, superiority trial

Background Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). Methods We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaounde, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per mu L, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1: 1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (< 50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059. Findings Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3.0%; 95% CI 0.8-7.6) of 132 participants on dual therapy and 33 (24.8%; 17.7-33.0) of 133 participants on monotherapy (relative risk 8.2, 95% CI 3.0-22.5; odds ratio 10.6, 95% CI 3.6-42.1). The difference between groups (21.8%, 95% CI 13.9-29.7; p< 0.0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung dise

Individual and healthcare supply-related barriers to treatment initiation in HIV-positive patients enrolled in the Cameroonian antiretroviral treatment access programme

International audienceIncreasing demand for antiretroviral treatment (ART) together with a reduction in international funding during the last decade may jeopardize access to ART. Using data from a cross-sectional survey conducted in 2014 in 19 HIV services in the Centre and Littoral regions in Cameroon, we investigated the role of healthcare supply-related factors in time to ART initiation in HIV-positive patients eligible for ART at HIV diagnosis. HIV service profiles were built using cluster analysis. Factors associated with time to ART initiation were identified using a multilevel Cox model. The study population included 847 HIV-positive patients (women 72%, median age: 39 years). Median (interquartile range) time to ART initiation was 1.6 (0.5-4.3) months. Four HIV service profiles were identified: (1) small services with a limited staff practising partial task-shifting (n = 4); (2) experienced and well-equipped services practising task-shifting and involving HIV community-based organizations (n = 5); (3) small services with limited resources and activities (n = 6); (4) small services providing a large range of activities using task-shifting and involving HIV community-based organizations (n = 4). The multivariable model showed that HIV-positive patients over 39 years old [hazard ratio: 1.26 (95% confidence interval) (1.09-1.45), P = 0.002], those with disease symptoms [1.21 (1.04-1.41), P = 0.015] and those with hepatitis B co-infection [2.31 (1.15-4.66), P = 0.019] were all more likely to initiate ART early. However, patients in the first profile were less likely to initiate ART early [0.80 (0.65-0.99), P = 0.049] than those in the second profile, as were patients in the third profile [association only significant at the 10% level; 0.86 (0.72-1.02), P = 0.090]. Our findings provide a better understanding of the role played by healthcare supply-related factors in ART initiation. In HIV services with limited capacity, task-shifting and support from community-based organizations may improve treatment access. Additional funding is required to relieve healthcare supply-related barriers and achieve the goal of universal ART access