Seventy-seven subjects infected with human immunodeficiency virus were randomized to switch from protease inhibitor (PI) therapy to nevirapine therapy (group A; n = 26) or to efavirenz therapy (group ...B; n = 25) or to continue PI therapy (group C; n = 26). At month 12, viral suppression had been maintained in 96% of patients in group A, 92% of patients in group B, and 92% of patients in group C. A significant increase in the CD4+ level was observed in all 3 groups. In group A, lipid profiles improved, whereas levels of γ-glutamiltransferase and alanine aminotransferase significantly increased; 1 subject interrupted treatment because of hepatotoxicity. In group B, an increase in γ-glutamiltransferase levels was also observed, and 3 patients interrupted treatment because of central nervous system symptoms. Two patients in group C withdrew therapy. Quality of life significantly improved for groups A and B. In patients receiving effective PI-based therapy, the replacement of the PI with either nevirapine or efavirenz is safe and virologically effective.
Individuals infected with human immunodeficiency virus (HIV) have an increased risk of progression to active tuberculosis following Mycobacterium tuberculosis infection. The objective of the study ...was to determine IFN-γ responses for the detection of latent tuberculosis infection (LTBI) with QuantiFERON-TB GOLD In Tube (QFT-G-IT) and T-SPOT.TB in HIV patients, and evaluate the influence of CD4 cell count on tests performance.
We studied 75 HIV patients enrolled for ongoing studies of LTBI with T-SPOT.TB, QFN-G-IT and TST. Mean CD4 cell counts ± standard deviation was 461.29 ± 307.49 cells/μl. Eight patients had a BCG scar.
T-SPOT.TB, QFN-G-IT and TST were positive in 7 (9.3%), 5 (6.7%) and 9 (12%) cases, respectively. Global agreement between QFN-G-IT and T-SPOT.TB was 89% (κ = 0.275). The overall agreement of T-SPOT.TB and QFN-G-IT with TST was 80.8% (κ = 0.019) and 89% (κ = 0.373), respectively. We have found negative IFN-γ assays results among 2 BCG-vaccinated HIV-infected individuals with a positive TST. In non BCG-vaccinated patients, QFN-G-IT and TST were positive in 5 cases (7.5%) and T-SPOT.TB in 7 (10.4%). In contrast, in BCG-vaccinated patients, only TST was positive in 4/8 (50%) of the cases. The differences obtained in the number of positive results between TST and both IFN-γ assays in BCG vaccinated patients were significant (95% CI 3-97%, p = 0.046), however, the confidence interval is very wide given the small number of patients. In patients with CD4< 200, we obtained only one (5%) positive result with T-SPOT.TB; however, QFN-G-IT and TST were negative in all cases. On the contrary, percentages of positive results in patients with CD4> 200 were 10.9% (6/55), 9.1% (5/55) and 16.4% (9/55) with T-SPOT.TB, QFN-G-IT and TST, respectively.
IFN-γ tests have the benefit over TST that are less influenced by BCG vaccination, consequently they are more specific than TST. Although our number of patients with advance immunosuppression is limited, our study suggests that IFN-γ assays are influenced with level of immunosuppression. The use of IFN-γ assays could be a helpful method for diagnosing LTBI in HIV population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the virological and immunological impact of a structured treatment interruption (STI) in a cohort of HIV-1 chronically infected patients with a further long-lasting effective virus ...suppression.
Twelve HIV-1 chronically infected adults who had maintained viral suppression (< 20 copies/ml) for more than 2 years, as well as a CD4:CD8 ratio > 1 for a median time of 22 months, were included in the study. Participants interrupted their antiretroviral treatment during a maximum period of 30 days or until a viral load rebound > 3000 copies/ml was detected. The same prior antiretroviral regimen was resumed after STI. Kinetics of plasma viral rebound was evaluated every 2 days during the treatment interruption period. Flow cytometry and cell proliferation assays were performed before and after STI. Genotypic resistance was assessed at the time of treatment resumption.
No adverse events occurred during the interruption period. In two patients no viral rebound was detected after 30 days of treatment interruption. In the remaining 10 patients, viral load became detectable (> 20 copies/ml) at a median time of 14 days after treatment interruption. Afterwards, viral load increased exponentially with a mean t1/2 of 1.6 days. Treatment was successfully resumed in all patients. No resistance-conferring mutations associated with the pre-interruption antiretroviral regimen were detected. The percentage of CD4 and CD8 lymphocytes did not vary during the STI period; however, the level of expression of T-cell activation antigen CD38 on CD8 T cells increased significantly in response to viral rebound. Four patients gained T-helper cell responses to recall antigens (tuberculin and tetanus toxoid), two of who developed an HIV-specific response to p24.
STI in chronically HIV-1-infected patients is not associated with reductions in CD4 T lymphocytes or to clinical complications in this group of patients after 2 years of effective plasma viral suppression. Viral load rebounds in most but not all patients, without evidence of selection of resistance-conferring mutations. Thereafter, viraemia can be effectively controlled by antiretroviral agent reintroduction. HIV-specific T-helper cell responses may be achieved after one cycle of treatment interruption suggesting some degree of immune-stimulation. These data do not discard consecutive cycles of STI as a therapeutic strategy to boost HIV-specific immunity in order to maintain viral replication under effective control.
The lack of available biomarkers for diagnosing and predicting different stages of liver disease with a noninvasive strategy is currently one of the main challenges that clinicians are facing. Recent ...evidence indicates that the plasma levels of specific microRNAs (miRNAs) may be significantly altered in patients with liver injury, including those with HIV type 1 (HIV-1) infections.
Large-scale deep sequencing analysis of small RNA expression was performed on plasma samples from 46 patients with HIV-1/hepatitis C virus (HCV) coinfections that did not exhibit liver fibrosis at the time of sampling.
A total of 1065 different miRNAs were identified. After a mean of 10.3 years, 26 out of the 46 patients developed liver fibrosis (stage F2-4) and 20 remained without signs of liver fibrosis (stage F0-1). We identified a signature of seven miRNAs: 100-5p, 192-5p, 99a-5p, 122-5p, 125b-2-3p, 1246 and 194-5p, which were highly correlated with progression to liver fibrosis. These seven miRNAs detected liver fibrosis progression with an area under the curve (AUC) of 0.910-0.806. Two miRNAs, 100-5p and 192-5p, which displayed the best AUC values, yielded a sensitivity of 88% and a specificity of 85% for detecting liver fibrosis progression.
Our results demonstrated that circulating miRNA levels had potential in predicting liver fibrosis progression before the clinical detection of liver fibrosis or significant clinical signs, such as elevated liver transaminases or platelets. Thus, our results might facilitate predictions of liver injury progression in patients with HIV-1-infections.
Guidelines recommendation to extend treatment duration in genotype 1 hepatitis C virus (HCV)/HIV-coinfected patients who clear the virus later than treatment week 4 is not evidence-based. Our main ...objective was to study the ability of week 12 viral response early virologic response (EVR) to predict long-term outcome in patients treated for 48 weeks.
Multicenter retrospective cohort analysis.
Genotype 1 HCV treatment-naive, HIV-coinfected adult patients with compensated liver disease who started combination therapy with fixed-dose pegylated-interferon (pegIFN) alfa-2a or weight-based pegIFN alfa-2b plus ribavirin were included. Univariate and forward stepwise logistic regression analysis were used to identify predictors of sustained viral response (SVR) and relapse.
By intention-to-treat analysis, 31.3% (87/278) of patients achieved an SVR. SVR rate was more than three-fold higher in patients who cleared the virus by week 12 of treatment compared with late responders. Among 123 end-of-treatment responders, 36 (29.3%) relapsed. Relapse risk increased in patients with cirrhosis, in those with ribavirin dose reductions and in late responders: more than 65% of patients who cleared the virus between weeks 12 and 24 relapsed following 48 weeks of treatment compared with 10% of those attaining a complete EVR (<15 IU/ml) at treatment week 12 (risk ratio 6.4, 95% confidence interval 2.9-14.4).
Viral response at treatment week 12 is a strong predictor of long-term outcome. Genotype 1 HCV/HIV-coinfected patients who achieve a complete EVR (<15 IU/ml) are at low risk of viral relapse after completing the standard 48 weeks of therapy.
HIV infection is believed to adversely affect the progression of hepatitis C virus (HCV)-related liver disease. However, information regarding HIV and HCV coinfection in the era of highly active ...antiretroviral therapy (HAART) is scarce. A cross-sectional study in 75 HCV/HIV-coinfected patients (most of them on HAART) and 75 HCV-monoinfected patients paired by age, sex, and date of liver biopsy analyzed the association of HIV infection with advanced liver fibrosis (Knodell fibrosis stages 3 + 4). The median CD4 cell count in HIV-coinfected patients was 546 cells/microl; 78.7% had an HIV-1 viral load <1000 copies/ml and 88% were on antiretroviral therapy. The percentage of patients harboring genotype 4 and with a higher HCV viral load was greater in the HIV-coinfected group. HCV/HIV-coinfected patients had more advanced liver fibrosis (Knodell fibrosis stages 3 + 4) than HCV-monoinfected patients (46.7% vs. 12%, p < 0.0001). In the univariate analysis, the factors associated with advanced liver disease were male sex (OR: 2.7, 95% CI: 1.05-7.1), history of injecting drug use (OR: 4.6, 95% CI: 2.0-10.2), HIV infection (OR: 6.4, 95% CI: 2.7-14.7), and previous exposure to therapy with protease inhibitors (OR: 3.0, 95% CI:1.4-6.3). In the multivariate analysis; only male sex (OR: 3.17, 95% CI: 1.152-8.773) and HIV infection (OR: 6.85, 95% CI: 2.93-16.005) were associated with advanced liver fibrosis. HIV infection is associated with advanced liver fibrosis. HIV/HCV-coinfected individuals on HAART are at risk of developing end-stage liver disease despite virological success and immunological reconstitution.
The spectrum of complications emerging in successfully treated HIV-infected patients has dramatically changed since the advent of HAART. Typical AIDS-defining illnesses have been substituted by new ...comorbid conditions that threaten even those patients who maintain virologic suppression. Proper management of cardiovascular risk, and early diagnosis of AIDS-related and, particularly, non-AIDS-related malignancies (including papilomavirus-related neoplasms) must be introduced into the routine of care. Hot areas of investigation include HIV-associated neurocognitive disorders, hepatitis B and C coinfection, non-alcoholic fatty liver disease, progressive multifocal leukoencephalopathy and tuberculosis. Bone and kidney long-term toxicities and lipoatrophy remain as issues of paramount importance. The identification and early treatment of immune reconstitution disease is also of major interest, specially in those patients starting their antiretroviral treatment with severe CD4 cell depletion. The present review focuses on these twelve areas of increasing interest for physicians currently facing successfully treated HIV+ patients.
A new transiently induced region (interferon-λ 4 protein; IFNL4) harbouring a dinucleotide variant ss469415590 (TT or ΔG), upstream of IFNL3 (IL28B), was recently found to be associated with ...hepatitis C virus (HCV) clearance. To determine the effect of IFLN4 ss469415590 variation on the HCV response to IFN-based therapy in HCV/HIV-1 coinfected patients, ss469415590 was genotyped in a cohort of 207 patients from our clinic. Treatment failure occurred in 77% of minor ΔG-allele carriers versus 48% of noncarriers, indicating that the ΔG allele was strongly associated with treatment failure. Importantly, multivariate logistic analysis revealed that ss469415590 genotype was a better predictor of treatment failure than rs12979860.
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