ABSTRACT
Background: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4+T-cell decline. We investigated host genetic factors associated with protection against CD4+T-cell loss in HIV-1-controllers. Methods: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4+T-cells counts >500 cells/mm3 for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4+T-cells counts <500 cells/mm3 Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined. Additionally, in a subgroup of individuals HIV-1-specific T-cell responses and soluble cytokines were analysed RESULTS: HLA-B*57 was independently associated with the LTNP-C phenotype (OR=3.056 (1.029-9.069) p=0.044 and OR=1.924 (1.252-2.957) p=0.003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590, OR=0.401 (0.171-0.942) p=0.036 or A/A, rs12980275, OR=0.637 (0.434-0.934) p=0.021) in the Spanish and validation cohort, respectively, after adjusting for sex, age at HIV-1 diagnosis, IFNL4-related polymorphisms and different HLA-B haplotypes. LTNP-C showed lower plasma IP-10 (p=0.019) and higher IFN-γ (p=0.02) levels than the HIV-1-controllers with diminished CD4+T-cell numbers. Moreover, LTNP-C exhibited higher quantities of IL2+CD57- and IFN-γ+CD57- HIV-1-specific CD8+T-cells (p=0.002 and 0.041, respectively) than non-LTNP-C. Conclusions: We have defined genetic markers able to segregate stable HIV-1-controllers from those who experience CD4+T-cell decline. These findings allow for identification of HIV-1-controllers at risk for immunologic progression, and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.
Subject(s)
Genetic Predisposition to Disease/genetics , HIV Infections/genetics , HLA-B Antigens/genetics , Interleukins/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Cohort Studies , Disease Progression , Female , Genetic Predisposition to Disease/epidemiology , HIV Infections/epidemiology , HIV-1 , Humans , Male , Young AdultABSTRACT
The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously cleared HCV, although 78% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV-coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV-1-positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment.
Subject(s)
Carrier Proteins/genetics , Genetic Variation , HIV Infections/complications , Hepacivirus/classification , Hepacivirus/genetics , Hepatitis C/virology , Viral Nonstructural Proteins/genetics , Carrier Proteins/metabolism , Cluster Analysis , Genotype , HIV Infections/virology , HIV-1/isolation & purification , Hepacivirus/enzymology , Hepacivirus/isolation & purification , Hepatitis C/epidemiology , Humans , Intracellular Signaling Peptides and Proteins , Male , Molecular Epidemiology , Molecular Sequence Data , Phylogeny , Proteolysis , RNA, Viral/genetics , Sequence Analysis, DNA , Viral Nonstructural Proteins/metabolismABSTRACT
OBJECTIVES: The aim of the study was to assess the progression of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients with no or mild-to-moderate fibrosis (stages F0-F2). METHODS: Liver fibrosis was reassessed by transient elastometry (TE) between January 2009 and November 2011 in HIV/HCV-coinfected patients with stage F0-F2 fibrosis in a liver biopsy performed between January 1997 and December 2007. Patients with liver stiffness at the end of follow-up < 7.1 kPa were defined as nonprogressors, and those with values ≥ 9.5 kPa or who died from liver disease were defined as progressors. Cirrhosis was defined as a cut-off of 14.6 kPa. The follow-up period was the time between liver biopsy and TE. Cox regression models adjusted for age, gender and liver fibrosis stage at baseline were applied. RESULTS: The median follow-up time was 7.8 years [interquartile range (IQR) 5.5-10 years]. The study population comprised 162 patients [115 (71%) nonprogressors and 47 (29%) progressors; 19 patients (11.7%) had cirrhosis]. The median time from the diagnosis of HCV infection to the end of follow-up was 20 years (IQR 16.3-23.1 years). Three progressors died from liver disease (1.8%). The variables associated with a lower risk of progression were age ≤ 38 years (hazard ratio (HR) 0.32; 95% confidence interval (CI) 0.16-0.62; P = 0.001], having received interferon (HR 2.18; 95% CI 1.14-4.15; P = 0.017), being hepatitis B virus surface antigen (HBsAg) negative (HR 0.20; 95% CI 0.04-0.92; P = 0.039), and baseline F0-F1 (HR 0.43; 95% CI 0.28-0.86; P = 0.017). CONCLUSIONS: A high proportion of patients with stage F0-F2 fibrosis progress to advanced liver fibrosis. Advanced liver fibrosis must be included in the list of diseases associated with aging. Our results support the recommendation to offer HCV antiviral therapy to HIV/HCV-coinfected patients at early stages of liver fibrosis.
Subject(s)
Antiviral Agents/therapeutic use , Coinfection/drug therapy , HIV Infections/drug therapy , Hepatitis C/drug therapy , Interferons/therapeutic use , Liver Cirrhosis/pathology , Ribavirin/therapeutic use , Adult , Age Factors , Antiretroviral Therapy, Highly Active , Antiviral Agents/administration & dosage , Disease Progression , Female , HIV Infections/complications , Hepatitis C/complications , Humans , Interferons/administration & dosage , Liver Cirrhosis/mortality , Male , Prospective Studies , Retrospective Studies , Ribavirin/administration & dosage , Risk FactorsABSTRACT
In this prospective, multicentre cohort study, we analysed specific prognostic factors and the impact of timing of highly active antiretroviral therapy (HAART) on disease progression and death among 625 human immunodeficiency virus (HIV)-1-infected, treatment-naïve patients diagnosed with an AIDS-defining disease. HAART was classified as early (<30 days) or late (30-270 days). Deferring HAART was significantly associated with faster progression to a new AIDS-defining event/death overall (p 0.009) and in patients with Pneumocystis jiroveci pneumonia (p 0.017). In the multivariate analysis, deferring HAART was associated with a higher risk of a new AIDS-defining event/death (p 0.002; hazard ratio 1.83; 95% CI 1.25-2.68). Other independent risk factors for poorer outcome were baseline diagnosis of AIDS-defining lymphoma, age >35 years, and low CD4(+) count (<50 cells/µL).
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Anti-Retroviral Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/mortality , Acquired Immunodeficiency Syndrome/mortality , Acquired Immunodeficiency Syndrome/virology , Adolescent , Adult , Cohort Studies , Female , HIV-1/isolation & purification , Humans , Male , Middle Aged , Multicenter Studies as Topic , Prognosis , Prospective Studies , Survival Analysis , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). METHODS: The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. RESULTS: Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/µL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. CONCLUSION: While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals.
Subject(s)
Anti-HIV Agents/therapeutic use , Drug Users/statistics & numerical data , HIV Infections/drug therapy , HIV Infections/mortality , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/mortality , AIDS-Related Opportunistic Infections/mortality , Adolescent , Adult , CD4 Lymphocyte Count , Cohort Studies , Disease Progression , Drug Therapy, Combination , Female , HIV Infections/etiology , HIV Infections/immunology , Humans , Male , Middle Aged , Odds Ratio , Proportional Hazards Models , RNA, Viral/blood , Risk Factors , Viral Load , Young AdultABSTRACT
Minority drug-resistant hepatitis C virus (HCV) variants may go undetected yet be clinically important. NS3/4A protease resistance substitutions V36A and A156S/T/V were selected in patients treated with protease inhibitors. The aim of this study was to investigate whether these substitutions pre-existed in HCV infected patients. An allele-specific PCR protocol that detected the NS3/4A protease resistance substitutions V36A and A156S/T/V was used to determine the prevalence of naturally occurring variants in 45 patients. All patient samples were infected with HCV of genotype 1b and were naïve for pegIFNα/ribavirin treatment. Thirty samples (67%) had at least one HCV PI-resistant variant. A156T (23, 51%) was detected more frequently than A156V (13, 29%) or A156S (1, 2%). V36A was detected in 12 samples (27%). These results demonstrate the high prevalence of minority drug-resistant NS3/4 protease resistance substitutions. Our results also demonstrate that allele-specific PCR can be used to detect minor HCV NS3 protease resistant variants in pretreatment samples and to study in detail the evolution of mutant viruses during targeted antiviral therapy.
Subject(s)
Antiviral Agents/metabolism , Carrier Proteins/antagonists & inhibitors , Drug Resistance, Viral , Hepacivirus/drug effects , Polymorphism, Genetic , Protease Inhibitors/metabolism , Viral Nonstructural Proteins/antagonists & inhibitors , Amino Acid Substitution , Carrier Proteins/genetics , Genotype , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C/drug therapy , Hepatitis C/virology , Humans , Interferons/administration & dosage , Intracellular Signaling Peptides and Proteins , Mutation, Missense , Polymerase Chain Reaction/methods , Ribavirin/administration & dosage , Viral Nonstructural Proteins/geneticsABSTRACT
UNLABELLED: Progression of liver fibrosis is associated with the risk of cirrhosis and end-stage liver disease. We aimed to evaluate fibrosis of the liver using three non-invasive indexes (FIB-4, Forns, and Pohl score) and its association with mortality of HCV-monoinfected and HCV/HIV-coinfected drug users. PATIENTS AND METHODS: longitudinal study in patients admitted to substance abuse treatment between 1994 and 2006. Socio-demographic data, drug use characteristics, blood samples for laboratory tests, and serology for HIV and hepatitis C virus infections were collected at admission. Patients were followed-up until December 2006 and mortality was ascertained through hospital charts and death certificates. RESULTS: Four hundred and ninety-seven patients were included (83.1% men); median age at admission was 31 years (IQR: 27-35). The main drugs of abuse were opiates (89.5%) and cocaine (8.3%). Thirty-two percent of patients reported daily alcohol consumption. The estimated prevalence of advanced liver fibrosis (ALF) was higher among HCV/HIV-coinfected patients (9.2% to 17.3% depending on the index analyzed) than among the HCV-monoinfected patients (3% to 3.5%). Odds ratio (OR) for ALF were 3.3 to 6.0 times higher in coinfected patients as compared to the HCV-monoinfected. After a median follow-up time of 7.7 years (IQR: 4.1-9.9 years), almost 20% of patients had died. The estimated ALF at admission was associated with an increased risk of death (RR 1.85 to 3.89 depending on the index). Among those with ALF, mortality rates were similar in HCV-monoinfected and HCV/HIV-coinfected patients, as determined by the FIB-4 and Forns indexes. CONCLUSIONS: Estimation of liver fibrosis using serum markers may help with clinical decisions to facilitate access to treatment of chronic hepatitis C in this population.
Subject(s)
HIV Infections/mortality , Hepatitis C/mortality , Liver Cirrhosis/diagnosis , Adult , Biomarkers/blood , Cohort Studies , Female , HIV Infections/complications , Hepatitis C/complications , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/epidemiology , Longitudinal Studies , Male , PrevalenceABSTRACT
BACKGROUND: Simple noninvasive tests to predict fibrosis, as an alternative to liver biopsy (LB), are needed. Of these, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and the Forns index (FI) have been validated in HIV/hepatitis C virus (HCV) coinfection. However, these indexes may have lower diagnostic value in situations other than the circumscribed conditions of validation studies. We therefore examined the value of the APRI and FI in HIV/HCV-coinfected patients for the detection of significant fibrosis in real-life conditions. PATIENTS AND METHODS: HIV/HCV-coinfected patients who had participated in a multicentre cross-sectional retrospective study were selected if they had undergone an LB within 24 months before the last visit. The predictive accuracy of the APRI and FI was measured using the areas under receiver-operating-characteristic curves (AUROCs). Diagnostic accuracy was determined using the positive (PPV) and negative (NPV) predictive values. RESULTS: A total of 519 coinfected individuals were included in the study. The AUROC [95% confidence interval (95% CI)] of the APRI was 0.67 (0.66-0.71) and that of the FI was 0.67 (0.62-0.71). The PPV of the APRI was 79% and its NPV was 66%. The PPV of the FI was 74% and its NPV was 64%. LB length was available and was > or =15 mm in 120 individuals. In this group, the PPV of the APRI was 85%, and that of the FI was 81%. Using these indexes, 22% of patients could be spared LB. Applying both models sequentially, 30% of patients could be spared LB. CONCLUSIONS: In HIV/HCV-coinfected patients, the diagnostic accuracy of the APRI in real-life conditions was similar to that in the validation studies. The FI performed less well. However, combining the two indexes to make decisions on anti-HCV therapy may prevent a significant proportion of patients from having to undergo LB.
Subject(s)
Aspartate Aminotransferases/blood , HIV Infections/complications , Hepatitis C/complications , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Adult , Biomarkers/blood , Biopsy , Cross-Sectional Studies , Female , HIV Infections/blood , Hepatitis C/blood , Humans , Liver Cirrhosis/blood , Male , Middle Aged , Platelet Count , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Young AdultABSTRACT
Transient elastometry (TE) could provide a more accurate evaluation of the frequency and risk factors of liver fibrosis in hepatitis C virus (HCV) infection than that based on biopsy. The aim of this study was to assess the prevalence of and factors associated with significant liver fibrosis in a large population of HIV/HCV-coinfected patients. HIV/HCV-coinfected patients, who had participated in a cross-sectional, multicenter, retrospective study of liver fibrosis using noninvasive markers and in whom a determination of liver stiffness (LS) by TE was available, were included in this analysis. Factors potentially associated with significant fibrosis (LS ≥ 9 kPa) were analyzed. One thousand three hundred and ten patients fulfilled the inclusion criteria, 526 (40%) of them showed LS ≥ 9 kPa and 316 (24%) cirrhosis (LS ≥ 14 kPa). The factors independently associated with significant fibrosis [adjusted odds ratio (95% confidence interval, P value) were the following: older age [1.04 (1.01-1.07), 0.002], daily alcohol intake > 50 g/day [1.58 (1.10-2.27), 0.013] and the length of HCV infection [1.03 (1.00-1.06), 0.023]]. A CD4 cell count lower than < 200 per mm(3) [1.67 (0.99-2.81), 0.053] and HCV genotype 4 [0.66 (0.42-1.02), 0.066] were marginally associated with LS ≥ 9 kPa. In conclusion, the prevalence of cirrhosis in HIV/HCV-coinfected patients seems to be higher than previously reported in studies based on liver biopsy. Older age, alcohol consumption and lower CD4 cell counts are related with significant fibrosis. The latter association supports an earlier starting of antiretroviral therapy in this setting.
Subject(s)
HIV Infections/complications , Hepatitis C, Chronic/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Adult , Cross-Sectional Studies , Elasticity Imaging Techniques/methods , Female , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVES: The two currently available types of pegylated interferon (peg-IFN) used to treat hepatitis C have different pharmacokinetic properties. It is unclear how these differences affect response to therapy. We compared the effectiveness and safety of peg-IFN-alpha2a and peg-IFN-alpha2b, both with ribavirin, against chronic hepatitis C virus (HCV) infection in HIV-infected patients. METHODS: From the GESIDA HIV/HCV cohort, we analysed patients treated with peg-IFN-alpha2a (n = 315) or peg-IFN-alpha2b (n = 242). The primary endpoint was a sustained virological response (SVR). RESULTS: Both groups were well matched in baseline characteristics except for a higher frequency of injection drug users in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (85% versus 76%; P = 0.01) and a higher frequency of bridging fibrosis and cirrhosis (F3-F4) in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (42% versus 33%; P = 0.04). End-of-treatment response was significantly lower among patients treated with peg-IFN-alpha2b [40% versus 52%; odds ratio (OR), 1.63; 95% confidence interval (95% CI), 1.16-2.29; P < 0.01]. However, no significant differences were found in SVR between patients treated with peg-IFN-alpha2b and those treated with peg-IFN-alpha2a (31% versus 33%; OR, 1.09; 95% CI, 0.75-1.59; P = 0.655). Therapy was interrupted due to adverse events in 33 (14%) patients treated with peg-IFN-alpha2b and 47 (15%) patients treated with peg-IFN-alpha2a. CONCLUSIONS: No differences in effectiveness and safety were found between peg-IFN-alpha2b and peg-IFN-alpha2a for the treatment of chronic HCV infection in HIV-infected patients.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Adult , Antiviral Agents/adverse effects , Female , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Polyethylene Glycols/adverse effects , Recombinant Proteins , Ribavirin/adverse effects , Treatment OutcomeABSTRACT
Chronic hepatitis C virus (HCV) infection follows an accelerated course in patients co-infected with human immunodeficiency virus (HIV); establishing the extent of liver fibrosis is crucial for disease staging and determining treatment strategy in these patients. The utility of noninvasive markers of fibrosis as alternatives to liver biopsy has not been well-studied in these patients. We evaluated the predictive value of serum transforming growth factor-beta1 (TGF-beta1) and hyaluronic acid (HA) levels for determining the extent of liver fibrosis. Liver biopsies and blood samples were collected from 69 consecutive patients (74% male; median age, 41 years) between May 2005 and November 2006. Serum TGF-beta1 and HA were analysed using commercial kits. Aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase levels were elevated in 81%, 70% and 60% of patients, respectively. Fifty-three patients (90%) were on highly active antiretroviral therapy and the median CD4-positive cell count was 422 cells/microL. The extent of fibrosis according to Scheuer's scoring was 32% F0 (no fibrosis), 16.5% F1, 16.5% F2, 26% F3 and 7% F4 (cirrhosis). Mean serum TGF-beta1 was 36.1 +/- 14.4 ng/mL; mean serum HA was 75.2 +/- 85.0 microg/L. Serum HA was positively associated and significantly correlated with the stage of fibrosis (r = 0.56; P < 0.05). The area under the curve for discriminating mild (F0-F2) from significant (F3-F4) fibrosis in receiver operating analysis using HA was 0.83 (sensitivity, 87%; specificity, 70%). These data suggest that HA is clinically useful for predicting liver fibrosis and cirrhosis in patients co-infected with HCV/HIV. However, serum TGF-beta1 was not predictive of histological damage in co-infected individuals treated with HAART.
Subject(s)
HIV Infections/complications , Hepatitis C, Chronic/complications , Hyaluronic Acid/blood , Liver Cirrhosis/diagnosis , Liver/pathology , Transforming Growth Factor beta1/blood , Adult , Biopsy , CD4 Lymphocyte Count , Female , Humans , Liver Cirrhosis/pathology , Liver Function Tests , Male , Middle Aged , Predictive Value of Tests , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.
Subject(s)
HIV Infections/complications , Hepatitis B/complications , Hepatitis C/complications , Liver Cirrhosis/diagnosis , Biomarkers/blood , Elasticity Imaging Techniques/methods , Humans , Prognosis , Severity of Illness IndexABSTRACT
BACKGROUND: Identification of recent HIV infections provides a description of the current pattern of HIV transmission and, consequently, can help to design better preventive interventions. Our study shows the first implementation in Spain of the Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) strategy. We assess the viability of introducing STARHS in our setting and describe the frequency and epidemiological characteristics of recent infections (RIs). METHODS: Between 2003 and 2005, HIV-positive blood samples drawn for diagnostic purposes were collected from 28 Spanish laboratories to be tested using STARHS. Samples from patients with a previous HIV diagnosis, age <18 years, <200 CD4 cells/microL or clinical AIDS criteria were excluded from the analysis. RESULTS: A total of 660 (19.2%) samples were classified as RI. Most people identified with RI were male (79.8%) with a median age of 33.1 years, and 62.5% occurred among men who have sex with men (MSM). Immigrants made up 26.5% of individuals identified with RIs, with 48.7% coming from South America. Among the individuals with RI, at least 16.5% had reported another sexually transmitted infection (STI) during the year before the HIV diagnosis. CONCLUSION: The study shows that the implementation of STARHS in our setting is feasible and has highlighted important features of the local HIV epidemic, such as the ongoing spread of HIV among MSM, the potential role of STIs in RIs and the vulnerability of immigrants as a new target population.
Subject(s)
AIDS Serodiagnosis/methods , HIV Seropositivity/epidemiology , HIV-1/immunology , Adult , Algorithms , Cross-Sectional Studies , Female , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Seropositivity/diagnosis , Humans , Male , Middle Aged , Spain/epidemiologyABSTRACT
OBJECTIVE: The aim of this study is to characterize the ways in which older HIV-infected people differ from younger HIV-infected people. METHODS: Prospective cohort study. PISCIS cohort includes newly attended HIV-infected subjects since January 1, 1998. Naive patients were selected. Two groups were defined: G1 (>or=50 years at time of diagnosis, n=493) and G2 (18-49 years, n=4511). Statistical analysis was performed using chi(2), Student's t test, Cox regression and linear mixed models. RESULTS: G1 had different features: males (G1: 84% vs. G2: 75%, p<0.001), sexual transmission (52% vs. 32%, p<0.001), AIDS at first visit (38% vs. 22%, p<0.001). The follow-up was 6 years. Ninety-five percent of patients in G1 and 92% in G2 presented a detectable viral load (>or=500 copies/mm(3)) at the first visit (p=0.016). G1 presented lower CD4 levels with respect to G2 throughout the period but the increase of CD4 in G1 at the end of the study period was 254 cells/mm(3) whereas for G2 it was 196 cells/mm(3) (p<0.001). Mortality was 9% for G1 and 4% for G2 (p<0.001). CONCLUSIONS: HIV-infected people diagnosed at the age of 50 years or older showed different features. They showed good viral and immunological response to HAART.
Subject(s)
HIV Infections , HIV-1 , Adolescent , Adult , Age Factors , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Cohort Studies , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/immunology , HIV Infections/virology , HIV-1/isolation & purification , HIV-1/physiology , Humans , Male , Middle Aged , Prognosis , RNA, Viral/blood , Viral LoadABSTRACT
OBJECTIVES: With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted. SUMMARY: Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy. With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present. CONCLUSIONS: Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/drug therapy , Hepatitis B, Chronic/drug therapy , Hepatitis C, Chronic/drug therapy , Adult , Antiretroviral Therapy, Highly Active , HIV Infections/complications , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , HumansABSTRACT
Within the framework of hepatitis C virus (HCV) prevalence monitoring, we evaluated oral fluid (OF), which is richer in IgG than whole saliva, as a possible alternative to serum for the detection of HCV antibodies. Paired OF and serum samples were collected from 90 individuals, including 45 HCV-positives and 45 HCV-negatives. The detection of HCV antibodies in both serum and OF was performed using the Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) (Ortho-Clinical Diagnostics, Inc., Raritan, NJ), but a modified, more sensitive protocol was used to process OF. The sensitivity and specificity of this assay were 86.67% (95% confidence interval (CI): 72.51-94.46%) and 100% (95% CI: 90.20-99.80%) in OF and 100% in serum. The correlation obtained between both types of clinical specimens was excellent (k: 0.87, 95% CI: 0.66-1.07). However, the negative predictive value (NPV) of the assay in OF decreased with the prevalence of HCV infection in the population studied. Our results suggest that the modified Ortho HCV 3.0 SAVe ELISA is suitable for the detection of HCV antibodies in OF for epidemiological studies. Using this assay, we observed an unadjusted anti-HCV prevalence of 78.6% among a population of intravenous drug users; when adjusted to account for assay sensitivity, this prevalence may be closer to 90%.
Subject(s)
Hepacivirus/immunology , Hepatitis C Antibodies/analysis , Hepatitis C/diagnosis , Hepatitis C/immunology , Saliva/immunology , Virology/methods , Adult , Enzyme-Linked Immunosorbent Assay/methods , Female , Hepatitis C/epidemiology , Hepatitis C Antibodies/blood , Humans , Male , Middle Aged , Predictive Value of Tests , Prevalence , Sensitivity and Specificity , Substance Abuse, IntravenousABSTRACT
To evaluate the safety and efficacy of an induction dose of pegylated interferon alpha 2a (IFN-alpha2a) on the 12-week hepatitis C virus (HCV) kinetics in human immunodeficiency virus (HIV) patients co-infected with HCV. One hundred sixteen HIV/HCV co-infected patients from nine hospitals in Spain were randomized to receive 270 microg/week of pegylated IFN-alpha2a for 4 weeks followed by 180 microg/week for 8 weeks or 180 microg/week for 12 weeks. Ribavirin was given at a daily dose of 1000 or 1200 mg. The main outcome measure was the percentage of patients achieving an HCV-RNA below 50 IU/mL or a decrease of 2 or more log(10) at week 12 (early virologic response, EVR). HCV-RNA was measured at baseline, weekly, for the first 4 weeks and monthly thereafter. We observed no difference in the percentage of patients achieving an EVR between arms (on-treatment, 74% in both arms; intention-to-treat, 70% in the induction arm and 67% in the control arm), nor were there differences in the percentage achieving an undetectable HCV qualitative polymerase chain reaction at any time points or in the decrease in HCV-RNA from baseline. No differences were found between arms in the percentage of dropouts (8% in the whole study population). Our study failed to find a benefit of an induction dose of 270 microg/week of pegylated IFN-alpha2a for 4 weeks on the EVR in co-infected patients who are treatment naive. Despite the lack of benefit with this regimen, induction therapy with this schedule was safe and well tolerated in co-infected patients.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , HIV-1 , Hepacivirus/isolation & purification , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Adult , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/drug therapy , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferon-alpha/administration & dosage , Male , Pilot Projects , Polyethylene Glycols/administration & dosage , Polymerase Chain Reaction , RNA, Viral/blood , Recombinant Proteins , Ribavirin/administration & dosage , Ribavirin/therapeutic use , Safety , Spain , Treatment Outcome , Viral LoadABSTRACT
This is a prospective observational comparative 48-week study to assess the impact of the different types of Peg-IFN on depressive and neuropsychiatric symptoms during treatment in HIV-HCV coinfected patients. Thirty-one patients treated with Peg-IFN alpha-2b 1.5 microg/kg/w plus ribavirine (RBV) (Peg-IFN alpha-2b Group) and 32 patients receiving Peg-IFN alpha-2a 180 microg/w plus RBV (Peg-IFN alpha-2a Group) were included. Depressive and neuropsychiatric symptoms, quality of life and adherence were assessed. Fifteen subjects (23%) discontinued therapy (p = 0.3, between groups). Overall, 37 patients presented mild to moderate depressive symptoms, 9 moderate to severe and 3 severe, without differences between groups. Patients in Peg-IFN alpha-2b reported higher fatigue and dizziness at weeks 12 (p < 0.05) and 24 (p < 0.05), and irritability and memory loss at week 24 (p < 0.05) with respect to Peg-IFN alpha-2a Group. At week 12, role functioning, general health perception, vitality, emotional role, mental health and the summary areas of physical health and mental health were lower in Peg-IFN alpha-2b Group (p < 0.05). The same was observed in physical functioning (p = 0.05) and role functioning, general health perception, emotional role and mental health (p < 0.001) at week 24. Three months after finishing treatment, no patient had depressive or neuropsychiatric symptoms, and quality of life improved. Antiretroviral adherence was low but adherence to anti-HCV therapy remained high in both groups. According to our data, Peg-IFN alpha-2a and Peg-IFN alpha-2b exert a similar impact on the overall rate of depressive symptoms, although patients treated with Peg-IFN alpha-2a experience less fatigue and fewer neuropsychiatric symptoms and a lower impairment in their physical and mental quality of life.
Subject(s)
Antiviral Agents/adverse effects , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Interferon-alpha/adverse effects , Mental Disorders/chemically induced , Polyethylene Glycols/adverse effects , Adult , Antidepressive Agents/therapeutic use , Drug Therapy, Combination , Female , HIV Infections/complications , Hepatitis C, Chronic/complications , Humans , Interferon alpha-2 , Male , Mental Disorders/prevention & control , Prospective Studies , Quality of Life/psychology , Recombinant Proteins , Recurrence , Ribavirin/therapeutic use , Treatment Refusal/psychologySubject(s)
Azithromycin/therapeutic use , Legionnaires' Disease/drug therapy , Levofloxacin , Ofloxacin/therapeutic use , AIDS-Related Opportunistic Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination , Female , Humans , Legionnaires' Disease/diagnostic imaging , Legionnaires' Disease/etiology , Lung/diagnostic imaging , Middle Aged , Radiography , Remission InductionABSTRACT
The aim of the study was to assess the incidence and the cumulative probability of cytolytic and cholestatic hepatotoxicity during antiretroviral treatment in a group of HIV HCV haemophiliacs. We evaluated 47 patients that received 246 courses of antiretroviral treatment [98 courses of pre-highly active antiretroviral therapy (pre-HAART) and 148 HAART treatments]. Liver function tests were assessed at baseline of each treatment, after 1 month and at least every 4 months thereafter. Cytolytic and cholestatic hepatotoxicity was recorded. Of the 246 treatments, 28 (12.45%) were followed by cytolytic hepatotoxicity and 32 (13%) by cholestatic hepatotoxicity. Cytolytic hepatotoxicity was similar in HAART (16/148; 10.8%) and in pre-HAART treatment (12/98; 12.2%) and cholestatic hepatotoxicity was more frequent in HAART (29/148; 19.6%) than in pre-HAART treatment (3/98; 3.1%) (P < 0.001). The actuarial probability of developing cytolytic and cholestatic hepatotoxicity at 10 years of onset of antiretroviral treatments was 39% and 56%, respectively. Most enzyme elevations were asymptomatic, but in eight cases therapy was discontinued or changed and in one case a cirrhotic patient died of progressive liver failure. In HIV HCV haemophiliacs, the cumulative probability of developing hepatotoxicity during follow-up is high and although in the most cases the toxicity is mild, fatal cases can occur.