CD4:CD8 ratio and CD8 count as prognostic markers for mortality in HIV-positive patients on ART:Antiretroviral Therapy Cohort Collaboration

We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count. We used data from 13 European and North American cohorts of human immunodeficiency virus-infected, antiretroviral therapy (ART)-naive adults who started ART during 1996-2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0-0.40, 0.41-0.64 [reference], >0.64) and CD8 count (0-760, 761-1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines. During 276526 person-years, 1834 of 49865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00-1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01-1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality. In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART

A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries

BACKGROUND: Mortality in HIV-infected patients has declined substantially with combination antiretroviral therapy (ART), but it is unclear whether it has reached that of the general population. We compared mortality in patients starting ART in nine countries of Europe and North America with the corresponding general population, taking into account their response to ART. METHODS: Eligible patients were enrolled in prospective cohort studies participating in the ART Cohort Collaboration. We calculated the ratio of observed to expected deaths from all causes [standardized mortality ratio (SMR)], measuring time from 6 months after starting ART, according to risk group, clinical stage at the start of ART and CD4 cell count and viral load at 6 months. Expected numbers of deaths were obtained from age-, sex- and country-specific mortality rates. RESULTS: Among 29 935 eligible patients, 1134 deaths were recorded in 131 510 person-years of follow-up. The median age was 37 years, 8162 (27%) patients were females, 4400 (15%) were injecting drug users (IDUs) and 6738 (23%) had AIDS when starting ART. At 6 months, 23 539 patients (79%) had viral load measurements or=350 cells/microL and suppressed viral replication to 10 were 4, 14 and 47%. CONCLUSIONS: In industrialized countries, the mortality experience of HIV-infected patients who start ART and survive the first 6 months continues to be higher than in the general population, but for many patients excess mortality is moderate and comparable with patients having other chronic conditions. Much of the excess mortality might be prevented by earlier diagnosis of HIV followed by timely initiation of ART

Determinants of restoration of CD4 and CD8 cell counts and their ratio in HIV-1 positive individuals with sustained virological suppression on antiretroviral therapy

Background: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV uninfected individuals more likely and whether restoration depends on gender, age and other individual characteristics. Methods: We determined median and quartile reference values for CD4 and CD8 cell count and their ratio using cross-sectional data from 2,309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed effects models. Results: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first two years median CD8 cell counts converged towards median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm3. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm3. Discussion: Starting ART with a CD4 cell count of ≥500 cells/mm3 makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals, because of persisting high CD8 cell counts. To what extent these subnormal immunological responses have impact on specific clinical endpoints requires further investigation

Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis

Objectives:To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure.Design:Collaborative analysis of data from eight European and three Canadian cohorts.Methods:Adults (N>20000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4(+) cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression.Results:The most prevalent subtypes were B (15419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104649 person-years of observation, 1172/20784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4(+) cell count below, or more than, 100 cells/l, respectively. There was no difference in mortality between subtypes A, B and C after viral failure.Conclusion:Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved