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1.
Hepatology ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31466125

RESUMO

BACKGROUND: HIV-HCV co-infected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, non-alcoholic steatohepatitis (NASH), a known risk factor for mortality. The fatty liver index (FLI), a non-invasive steatosis biomarker, has recently drawn attention for its clinical prognostic value, although its capacity to predict mortality risk in HIV-HCV co-infected patients has never been investigated. Using a Cox proportional hazards model for mortality from all causes, with data from the French ANRS CO13 HEPAVIH cohort (983 patients; 4,432 visits), we tested whether elevated FLI (≥60) was associated with all-cause mortality. MAIN RESULTS: After multiple adjustment, individuals with FLI≥60 had almost double the risk of all-cause mortality (adjusted hazard ratio [95% confidence interval]: 1.91 [1.17-3.12], p = 0.009), independently of the following factors: HCV cure (0.21 [0.07-0.61], p=0.004), advanced fibrosis (1.77 [1.00-3.14], p=0.05), history of hepatocellular carcinoma and/or liver transplantation (7.74 [3.82-15.69], p<10-3 ), history of indirect clinical signs of cirrhosis (2.80 [1.22-6.41], p=0.015), and HIV CDC clinical stage C (2.88 [1.74-4.79], p<10-3 ). CONCLUSION: An elevated fatty liver index (FLI≥60) is a risk factor for all-cause mortality in HIV-HCV co-infected patients independently of liver fibrosis and HCV cure. In the present era of nearly 100% HCV cure rates thanks to direct-acting antivirals, these findings encourage the more systematic use of non-invasive steatosis biomarkers to help identify co-infected patients with higher mortality risk. This article is protected by copyright. All rights reserved.

2.
AIDS Behav ; 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286317

RESUMO

Mortality among individuals co-infected with HIV and hepatitis C virus (HCV) is relatively high. We evaluated the association between psychoactive substance use and both HCV and non-HCV mortality in HIV/HCV co-infected patients in France, using Fine and Gray's competing-risk model adjusted for socio-demographic, clinical predictors and confounding factors, while accounting for competing causes of death. Over a 5-year median follow-up period, 77 deaths occurred among 1028 patients. Regular/daily cannabis use, elevated coffee intake, and not currently smoking were independently associated with reduced HCV-mortality (adjusted sub-hazard ratio [95% CI] 0.28 [0.10-0.83], 0.38 [0.15-0.95], and 0.28 [0.10-0.79], respectively). Obesity and severe thinness were associated with increased HCV-mortality (2.44 [1.00-5.93] and 7.25 [2.22-23.6] versus normal weight, respectively). Regular binge drinking was associated with increased non-HCV-mortality (2.19 [1.10-4.37]). Further research is needed to understand the causal mechanisms involved. People living with HIV/HCV co-infection should be referred for tobacco, alcohol and weight control interventions and potential benefits of cannabis-based therapies investigated.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31094856

RESUMO

OBJECTIVES: Although common among patients coinfected with HIV and hepatitis C virus (HCV), sleep disturbances (SD) are still poorly documented in this population in the HCV cure era. This longitudinal study aimed at analysing SD in HIV-HCV coinfected patients and identifying their clinical and sociobehavioural correlates. METHODS: We used 5-year annual follow-up data from 1047 participants in the French National Agency for Research on Aids and Viral Hepatitis Cohort 13 'Hépatite et VIH' (ANRS CO13 HEPAVIH) cohort of HIV-HCV coinfected patients to identify clinical (medical records) and behavioural (self-administered questionnaires) correlates of SD (mixed-effects logistic regression). SD were identified using one item documenting the occurrence of insomnia or difficulty falling asleep (ANRS 'Action Coordonnée 24' self-reported symptoms checklist), and two items documenting perceived sleep quality (Center for Epidemiologic Studies Depression and WHO Quality of Life HIV-specific brief scales). RESULTS: Seven hundred and sixteen (68.4%) patients with completed self-administered questionnaires reported SD at their most recent follow-up visit. In the multivariable model, hazardous alcohol consumption (Alcohol Use Disorders Identification Test-Consumption score≥4 for men, ≥3 for women) (adjusted odds ratio=1.61; 95% confidence interval: 1.09-2.36), depressive symptoms (6.78; 4.36-10.55) and the number of other physical and psychological self-reported symptoms (1.10; 1.07-1.13) were associated independently with SD after adjustment for sex, age and employment status. HCV cure was not associated significantly with SD. CONCLUSION: SD remain frequent in HIV-HCV coinfected patients and are associated with a series of modifiable behavioural risk factors. Independent of HCV cure, improved screening and comprehensive management of alcohol use, physical and psychological self-reported symptoms and depression are essential in this population. Closer investigation of these risk factors of SDs may both increase sleep quality and indirectly improve patients' clinical outcomes.

5.
Am J Epidemiol ; 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063192

RESUMO

Effect estimates from randomized trials and observational studies may not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a three-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocol (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive to the human immunodeficiency virus from the START randomized trial and the observational HIV-CAUSAL Collaboration.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31033848

RESUMO

OBJECTIVES: HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients. PATIENTS AND METHODS: HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization. RESULTS: A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively. CONCLUSION: To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.

7.
PLoS One ; 14(1): e0211286, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682180

RESUMO

BACKGROUND: The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. METHODS: HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. RESULTS: 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. CONCLUSION: Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

9.
J Acquir Immune Defic Syndr ; 80(4): 461-466, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30570526

RESUMO

BACKGROUND: Hepatitis C virus (HCV) and HIV infections are associated with higher risk of autoimmune diseases and T-cell dysfunction. SETTING: We evaluate prevalence and factors associated with the presence of autoimmune antinuclear (ANA), anti-smooth muscle actin (aSMA), and anti-liver kidney microsome (aLKM1) antibodies (Ab) in HCV/HIV-coinfected patients during the post-combined antiretroviral therapy era. METHODS: A cross-sectional observational study nested in the ANRS CO13 HEPAVIH cohort (NCT number: NCT03324633). We selected patients with both ANA testing and T-cell immunophenotyping determination during the cohort follow-up and collected aLKM1 and aSMA data when available. Logistic regression models were built to determine factors associated with the presence of auto-Ab. RESULTS: Two hundred twenty-three HCV/HIV-coinfected patients fulfilled selection criteria. Prevalence of ANA and aSMA was 43.5% and 23.2%, respectively, and both were detected in 13.3% of patients. Isolated aSMA were detected in 9.9% and aLKM1 in 2 patients. In multivariable analysis, only a low nadir CD4 T-cell count was significantly associated with ANA detection. CONCLUSIONS: ANA and aSMA detection remain frequent in HCV/HIV-coinfected patients during the post-combined antiretroviral therapy era, despite fair immune restoration. These results advocate for a close monitoring of ANA before immune checkpoint inhibitor therapy in these patients with greater caution for those with a low nadir CD4 T-cell count.

10.
Hepatology ; 70(3): 939-954, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30569448

RESUMO

It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child-Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine-Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow-up similar rates of HCV eradication than HCV mono-infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5-year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co-infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15-3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV-infected patients with cirrhosis, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions.

11.
BMC Med Res Methodol ; 18(1): 159, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514234

RESUMO

BACKGROUND: Biological assays for the quantification of markers may suffer from a lack of sensitivity and thus from an analytical detection limit. This is the case of human immunodeficiency virus (HIV) viral load. Below this threshold the exact value is unknown and values are consequently left-censored. Statistical methods have been proposed to deal with left-censoring but few are adapted in the context of high-dimensional data. METHODS: We propose to reverse the Buckley-James least squares algorithm to handle left-censored data enhanced with a Lasso regularization to accommodate high-dimensional predictors. We present a Lasso-regularized Buckley-James least squares method with both non-parametric imputation using Kaplan-Meier and parametric imputation based on the Gaussian distribution, which is typically assumed for HIV viral load data after logarithmic transformation. Cross-validation for parameter-tuning is based on an appropriate loss function that takes into account the different contributions of censored and uncensored observations. We specify how these techniques can be easily implemented using available R packages. The Lasso-regularized Buckley-James least square method was compared to simple imputation strategies to predict the response to antiretroviral therapy measured by HIV viral load according to the HIV genotypic mutations. We used a dataset composed of several clinical trials and cohorts from the Forum for Collaborative HIV Research (HIV Med. 2008;7:27-40). The proposed methods were also assessed on simulated data mimicking the observed data. RESULTS: Approaches accounting for left-censoring outperformed simple imputation methods in a high-dimensional setting. The Gaussian Buckley-James method with cross-validation based on the appropriate loss function showed the lowest prediction error on simulated data and, using real data, the most valid results according to the current literature on HIV mutations. CONCLUSIONS: The proposed approach deals with high-dimensional predictors and left-censored outcomes and has shown its interest for predicting HIV viral load according to HIV mutations.

12.
PLoS One ; 13(12): e0208657, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30562358

RESUMO

Compared to the general population, HIV-infected patients are at higher risk of developing non-AIDS-defining cancers. Chronic HCV infection has also been associated with a higher risk than that of the general population of developing cancers other than hepatocarcinoma. Evaluation of the impact of HCV-related factors on non-AIDS-defining and non HCV-liver (NANL) related cancers among HIV/HCV co-infected patients are scarce. The aim of this study was to identify the impact of HIV/HCV clinical characteristics on NANL related cancers in a large cohort of HIV/HCV-coinfected patients followed from 2005 to 2017. Cox proportional hazards models with delayed entry were used to estimate factors associated with NANL related cancer. Among 1391 patients followed for a median of 5 years, 60 patients developed NANL related cancers, yielding an incidence rate of 8.9 per 1000 person-years (95% CI, [6.6-11.1]). By final multivariable analysis, after adjustment for sex, tobacco or alcohol consumption, baseline CD4 cell count and HCV sustained viral response (SVR), age and a longer duration since HIV diagnosis were independently associated with a higher risk of NANL related cancer (aHR for each additional year 1.10, 95% CI 1.06-1.14, p<0.0001 and 1.06, 95% CI 1.01-1.11, p = 0.02, respectively). Duration of HCV infection, cirrhosis, HCV viral load, genotype and SVR were not associated with the occurrence of NANL related cancer. Among HIV/HCV-coinfected patients, age and the duration of HIV infection were the only characteristics found to be associated with the occurrence of NANL related cancer. In contrast, no association was observed with any HCV-related variables.


Assuntos
Infecções por HIV/epidemiologia , Hepatite C/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adulto , Coinfecção , Feminino , Humanos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
14.
PLoS One ; 13(7): e0199874, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29975764

RESUMO

BACKGROUND: Direct-acting antivirals (DAA) have dramatically increased HCV cure rates with minimal toxicity in HIV-HCV co-infected patients. This study aimed to compare the socio-behavioral characteristics of patients initiating pegylated-interferon (PEG-IFN)-based HCV treatment with those of patients initiating DAA-based treatment. METHODS: ANRS CO13 HEPAVIH is a national multicenter prospective cohort started in 2005, which enrolled 1,859 HIV-HCV co-infected patients followed up in French hospital outpatient units. Both clinical/biological and socio-behavioral data were collected during follow-up. We selected patients with socio-behavioral data available before HCV treatment initiation. RESULTS: A total of 580 patients were included in this analysis. Of these, 347 initiated PEG-IFN-based treatment, and 233 DAA-based treatment. There were significant differences regarding patient mean age (45 years±6 for the PEG-IFN group vs. 52 years±8 for the DAA group, p<0.001), unstable housing (21.4% vs. 11.2%, p = 0.0016), drug use (44.7% vs. 29.6%, p = 0.0003), regular or daily use of cannabis (24.3% vs. 15.6%, p = 0.0002), a history of drug injection (68.9% vs 39.0%, p<0.0001) and significant liver fibrosis (62.4% vs 72.3%, p = 0.0293). In multivariable analysis, patients initiating DAA-based treatment were older than their PEG-IFN-based treatment counterparts (aOR = 1.17; 95%CI [1.13; 1.22]). Patients receiving DAA treatment were less likely to report unstable housing (0.46 [0.24; 0.88]), cannabis use (regular or daily use:0.50 [0.28; 0.91]; non-regular use: 0.41 [0.22; 0.77]), and a history of drug injection (0.19 [0.12; 0.31]). CONCLUSION: It is possible that a majority of patients who had socio-economic problems and/or a history of drug injection and/or a non-advanced disease stage were already treated for HCV in the PEG-IFN era. Today, patients with unstable housing conditions are prescribed DAA less frequently than other populations. As HCV treatment is prevention, improving access to DAA remains a major clinical and public health strategy, in particular for individuals with high-risk behaviors.

15.
Nutrients ; 10(6)2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29857547

RESUMO

BACKGROUND: Coffee intake has been shown to modulate both the effect of ethanol on serum GGT activities in some alcohol consumers and the risk of alcoholic cirrhosis in some patients with chronic diseases. This study aimed to analyze the impact of coffee intake and alcohol consumption on advanced liver fibrosis (ALF) in HIV-HCV co-infected patients. METHODS: ANRS CO13-HEPAVIH is a French, nationwide, multicenter cohort of HIV-HCV-co-infected patients. Sociodemographic, behavioral, and clinical data including alcohol and coffee consumption were prospectively collected using annual self-administered questionnaires during five years of follow-up. Mixed logistic regression models were performed, relating coffee intake and alcohol consumption to ALF. RESULTS: 1019 patients were included. At the last available visit, 5.8% reported high-risk alcohol consumption, 27.4% reported high coffee intake and 14.5% had ALF. Compared with patients with low coffee intake and high-risk alcohol consumption, patients with low coffee intake and low-risk alcohol consumption had a lower risk of ALF (aOR (95% CI) 0.24 (0.12⁻0.50)). In addition, patients with high coffee intake had a lower risk of ALF than the reference group (0.14 (0.03⁻0.64) in high-risk alcohol drinkers and 0.11 (0.05⁻0.25) in low-risk alcohol drinkers). CONCLUSIONS: High coffee intake was associated with a low risk of liver fibrosis even in HIV-HCV co-infected patients with high-risk alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Café/efeitos adversos , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Fígado/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos de Coortes , Progressão da Doença , Feminino , França/epidemiologia , Infecções por HIV/sangue , Infecções por HIV/virologia , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Autorrelato , Índice de Gravidade de Doença
16.
AIDS ; 32(10): 1361-1367, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29851663

RESUMO

OBJECTIVE: Model trajectories of CD4 and CD8 cell counts after starting combination antiretroviral therapy (ART) and use the model to predict trends in these counts and the CD4 : CD8 ratio. DESIGN: Cohort study of antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with more than 6 months of follow-up data. METHODS: We jointly estimated CD4 and CD8 cell count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4 : CD8 ratio trend from this model. We assessed whether CD4 and CD8 cell count trends and the CD4 : CD8 ratio trend varied according to CD4 cell count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. RESULTS: A total of 39 979 patients were included (median follow-up was 53 months). Among patients with baseline CD4 cell count at least 50 cells/µl, predicted mean CD8 cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4 : CD8 ratio. During 15 years of follow-up, normalization of the predicted mean CD4 : CD8 ratio (to >1) was only observed among patients with baseline CD4 cell count at least 200 cells/µl. A higher baseline CD4 cell count predicted a shorter time to normalization. CONCLUSION: Declines in CD8 cell count and increases in CD4 : CD8 ratio occurred up to 15 years after starting ART. The likelihood of normalization of the CD4 : CD8 ratio is strongly related to baseline CD4 cell count.

17.
AIDS ; 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29734221

RESUMO

OBJECTIVE: Model trajectories of CD4 and CD8 cell counts after starting combination antiretroviral therapy (ART), and use the model to predict trends in these counts and the CD4:CD8 ratio. DESIGN: Cohort study of antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with >6 months of follow-up data. METHODS: We jointly estimated CD4 and CD8 count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4:CD8 ratio trend from this model. We assessed whether CD4 and CD8 count trends and the CD4:CD8 ratio trend varied according to CD4 count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. RESULTS: A total of 39,979 patients were included (median follow-up was 53 months). Among patients with baseline CD4 count ≥50 cells/mm, predicted mean CD8 counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4:CD8 ratio. During 15 years of follow-up, normalisation of the predicted mean CD4:CD8 ratio (to >1) was only observed among patients with baseline CD4 count ≥200 cells/mm. A higher baseline CD4 count predicted a shorter time to normalisation. CONCLUSIONS: Declines in CD8 count and increases in CD4:CD8 ratio occurred up to 15 years after starting ART. The likelihood of normalisation of the CD4:CD8 ratio is strongly related to baseline CD4 count.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

20.
J Antimicrob Chemother ; 72(10): 2869-2878, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29091198

RESUMO

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Estudos de Coortes , Europa (Continente) , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Carga Viral
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