Our objective was to study the prognostic value of liver stiffness (LS) in HIV-infected patients with chronic hepatitis C (CHC).
We analyzed HIV-infected patients with compensated CHC and at least 1 ...determination of LS. The primary outcome was the occurrence of liver-related events (LRE), namely, decompensation or hepatocellular carcinoma, whichever occurred first. We selected patients without sustained viral response (SVR) or end-of-treatment response (ETR) during follow-up and allocated them to an estimation cohort (EC) and a validation cohort (VC).
The study population comprised 1292 patients. After a median follow-up of 5.8 years, 90 patients experienced LRE and 73 died. In the subgroup of 957 patients without SVR or ETR, the area under the receiver operating characteristic curves (AUROCs) (95% confidence interval CI) of LS for prediction of LRE in the EC (n = 634) and the VC (n = 323) were 0.87 and 0.88, respectively. The best cutoff value of LS to rule out LRE in the EC was 12 kPa, with a negative predictive value of 98.3% in the EC and 98.2% in the VC. Per each 1 kPa and 5 kPa increase above 12 kPa, the hazard ratio of LRE (taking into account death as a competing risk) was 1.07 (95% CI, 1.05-1.08) and 1.38 (95% CI, 1.31-1.46), respectively.
Liver stiffness is very accurate for predicting LRE in coinfected patients. Patients with an LS <12 kPa had a 98% probability of not developing LRE after a median follow-up of almost 6 years. Above the 12-kPa cutoff, the hazard of LRE increases proportionally with LS.
Summary Objectives To analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004–2013). Methods Cox models and logistic ...regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS. Results Of 7165 new HIV diagnoses, 46.9% (CI95% :45.7–48.0) were LP, 240 patients died. First-year mortality was the highest (aHRLP.vs.nLP = 10.3CI95% :5.5–19.3); between 1 and 4 years post-diagnosis, aHRLP.vs.nLP = 1.9(1.2–3.0); and >4 years, aHRLP.vs.nLP = 1.5(0.7–3.1). First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p < 0.001). LP declined from 55.9% (2004–05) to 39.4% (2012–13), and reduced in 46.1% in men who have sex with men (MSM) and 37.6% in heterosexual men, but increased in 22.6% in heterosexual women. Factors associated with LP: sex (ORMEN.vs.WOMEN = 1.41.2–1.7); age (OR31–40.vs.<30 = 1.61.4–1.8, OR41–50.vs.<30 = 2.21.8–2.6, OR>50.vs.<30 = 3.62.9–4.4); behavior (ORInjectedDrugUse.vs.MSM = 2.82.0–3.8; ORHeterosexual.vs.MSM = 2.21.7–3.0); education (ORPrimaryEducation.vs.University = 1.51.1–2.0, ORLowerSecondary.vs.University = 1.31.1–1.5); and geographical origin (ORSub-Saharan.vs.Spain = 1.61.3–2.0, ORLatin-American.vs.Spain = 1.41.2–1.8). Conclusions LP is associated with higher mortality, especially short-term- and HIV/AIDS-related mortality. Mid-term-, but not long-term mortality, remained also higher in LP than nLP. LP decreased in MSM and heterosexual men, not in heterosexual women. The groups most affected by LP are low educated, non-Spanish and heterosexual women.
To analyze the relationship of SLC30A8 rs13266634 polymorphism with insulin resistance and dyslipidemia in HIV/hepatitis C virus (HCV)-coinfected patients.
Cross-sectional study in 260 ...HIV/HVC-coinfected patients.
SLC30A8 polymorphisms were genotyped by GoldenGate assay. Genetic data were analyzed under the dominant inheritance model (CT/TT versus CC). Cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), LDL-C/HDL-C, atherogenic index, and homeostatic model assessment of insulin resistance (HOMA-IR) values were assayed for each genotype.
rs13266634 CT/TT carriers had higher serum values of HDL-C (P = 0.014) and lower values of LDL-C/HDL-C (P = 0.036) and atherogenic index (P = 0.011) than CC carriers. Additionally, rs13266634 CT/TT carriers had lower percentage of HDL 35 mg/dl or less (P = 0.050) and higher percentage of LDL/HDL at least 3 (P = 0.091) and atherogenic index at least 3.5 (P = 0.003) than CC carriers. When adjusted regression analysis was performed, rs13266634 CT/TT genotype was associated with high serum values of HDL-C arithmetic mean ratio (AMR) = 1.10 (95% confidence interval, CI = 1.03-1.19) P = 0.006, and low values of LDL-C/HDL-C AMR = 0.88 (95% CI = 0.79-0.99) P = 0.045 and atherogenic index AMR = 0.89 (95% CI = 0.81-0.98) P = 0.024. For categorical outcomes, rs13266634 CT/TT carriers had lower significant likelihood of having atherogenic index at least 3.5 odds ratio = 0.47 (95% CI = 0.26-0.83) P = 0.009, and very close to significance for LDL-C/HDL-C at least 3 odds ratio = 0.52 (95% CI = 0.27-1.02) P = 0.056, supporting the protective effect of the CT/TT genotypes. No significant relationship was observed between rs13266634 and HOMA-IR values.
rs13266634 CT/TT genotype was associated to higher levels of HDL-C and lower values of cardiovascular risk indices (LDL-C/HDL-C and atherogenic index), but there was a lack of association with HOMA-IR values. Thus, rs13266634 polymorphism might play a significant role in lipid metabolism and cardiovascular risk in HIV/HCV-coinfected patients.
Background
The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum ...dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)‐coinfected patients.
Methods
We carried out a cross‐sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate® assay. Generalized linear models (GLMs) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), non‐HDL‐C and homeostatic model assessment (HOMA)) and categorical outcome variables (TC ≥ 200 mg/dL, TG ≥ 170 mg/dL, LDL‐C ≥ 100 mg/dL, HDL‐C ≤ 35 mg/dL, non‐HDL‐C ≥ 120 mg/dL and HOMA ≥ 3·8) according to ADIPOQ genotype under a dominant inheritance model.
Results
Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (P = 0·038) and percentages of TC ≥ 200 mg/dL (P = 0·022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (arithmetic mean ratio (AMR) = 0·92 (95% CI = 0·85; 0·99) P = 0·024) and low likelihood of TC ≥ 200 mg/dL (odds ratio (OR) = 0·32 (95% CI = 0·11; 0·88) P = 0·027. When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR = 0·89; P = 0·027), LDL‐C (AMR = 0·85; P = 0·039) and non‐HDL‐C (AMR = 0·86; P = 0·015). No significant associations were found between rs2241766 and HOMA values.
Conclusions
The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV‐coinfected patients with steatosis.
The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile ...in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response.
miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms.
A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response.
Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non-infected individuals. Moreover, a specific miRNA pattern is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern in terms of CD8+ T-cell immune response.
We assessed the effect of co-infection by hepatitis C virus (HCV) on immunological and virological response at 48 weeks from initiation of antiretroviral therapy (ART).We included patients from the ...Cohort of Spanish HIV Research Network (CoRIS) starting ART between January 2004 and November 2014, had at least 1 CD4 T-cell count and viral load measurements both in the previous 6 months and at 48 (±12) weeks from ART initiation, and HCV serology before ART initiation. We used linear regression for mean differences in CD4 T-cell count increase from ART initiation and logistic regression to estimate odds ratios for virological response.Of 12,239 patients by November 30, 2015, 5070 met inclusion criteria: 4382 (86.4%) HIV mono-infected and 688 (13.6%) HIV/HCV co-infected. Co-infected patients were more likely to have acquired HIV through injecting drugs use (57.4% vs. 1.1%), to be women, older, and Spanish, have a lower educational level, and having started ART with lower CD4 counts and acquired immunodeficiency syndrome. CD4 T-cell count increase at 48 weeks was 229.7 cell/μL in HIV-monoinfected and 161.9 cell/μL in HIV/HCV-coinfected patients. The percentages of patients achieving a virological response at 48 weeks were 87.0% and 78.3% in mono and coinfected patients, respectively. Multivariable analyses showed that at 48 weeks, coinfected patients increased 44.5 (95% confidence interval CI: 24.8-64.3) cells/μL less than monoinfected and had lower probability of virological response (odds ratio: 0.62; 95% CI: 0.44-0.88).HIV/HCV-coinfected patients have lower immunological and virological responses at 48 weeks from ART initiation than monoinfected patients.
Outcomes of people living with HIV (PLWH) developing non-AIDS events (NAEs) remain poorly defined. We aimed to classify NAEs according to severity, and to describe clinical outcomes and prognostic ...factors after NAE occurrence using data from CoRIS, a large Spanish HIV cohort from 2004 to 2013.
Prospective multicenter cohort study.
Using a multistate approach we estimated 3 transition probabilities: from alive and NAE-free to alive and NAE-experienced ("NAE development"); from alive and NAE-experienced to death ("Death after NAE"); and from alive and NAE-free to death ("Death without NAE"). We analyzed the effect of different covariates, including demographic, immunologic and virologic data, on death or NAE development, based on estimates of hazard ratios (HR). We focused on the transition "Death after NAE".
8,789 PLWH were followed-up until death, cohort censoring or loss to follow-up. 792 first incident NAEs occurred in 9.01% PLWH (incidence rate 28.76; 95% confidence interval CI, 26.80-30.84, per 1000 patient-years). 112 (14.14%) NAE-experienced PLWH and 240 (2.73%) NAE-free PLWH died. Adjusted HR for the transition "Death after NAE" was 12.1 (95%CI, 4.90-29.89). There was a graded increase in the adjusted HRs for mortality according to NAE severity category: HR (95%CI), 4.02 (2.45-6.57) for intermediate-severity; and 9.85 (5.45-17.81) for serious NAEs compared to low-severity NAEs. Male sex (HR 2.04; 95% CI, 1.11-3.84), age>50 years (1.78, 1.08-2.94), hepatitis C-coinfection (2.52, 1.38-4.61), lower CD4 cell count at cohort entry (HR 2.49; 95%CI 1.20-5.14 for CD4 cell count below 200 and HR 2.16; 95%CI 1.01-4.66 for CD4 cell count between 200-350, both compared to CD4 cell count higher than 500) and concomitant CD4<200 cells/mL (2.22, 1.42-3.44) were associated with death after NAE. CD4 count and HIV-1 RNA at engagement, previous AIDS and hepatitis C-coinfection predicted mortality in NAE-free persons.
NAEs, including low-severity events, increase prominently the risk for mortality in PLWH. Prognostic factors differ between NAE-experienced and NAE-free persons. These findings should be taken into account in the clinical management of PLWH developing NAEs and may permit more targeted prevention efforts.
The mechanisms involved in the chronic hepatitis C progression are incompletely understood. The aim was to analyze the association between 2'5'oligoadenylate synthetase 1,2 and 3 (OAS1-3) and ...myxovirus resistance proteins 1 (Mx1) polymorphisms and severity of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. We performed a cross-sectional study in 219 patients that underwent a liver biopsy. DNA genotyping for Mx1 (rs469390), OAS1 (rs2285934), OAS2 (rs1293762) and OAS3 (rs2010604) was performed by using GoldenGate assay. The outcome variables ion liver biopsy were: (i) significant fibrosis (F ≥ 2); (ii) moderate activity grade (A ≥ 2). Additive model of inheritance for genetic association test was used. The likelihood of having significant fibrosis (F ≥ 2) was lower in patients carrying OAS2 rs1293762 A allele adjusted odds ratio (aOR) = 0.51; p = 0.040. Besides, the likelihood of having moderate activity grade (A ≥ 2) was higher in patients carrying Mx1 rs464397 C allele (aOR = 1.63; p = 0.028) and Mx1 rs469390 G allele (aOR = 1.97; p = 0.005), while it was lower in patients carrying OAS1 rs2285934 A allele (aOR = 0.64; p = 0.039) and OAS2 rs1293762 A allele (aOR = 0.41; p = 0.009). In conclusion, Mx1 and OAS1-2 polymorphisms were associated with the severity of liver disease in HIV/HCV-coinfected patients, suggesting a significant role in the progression of hepatic fibrosis.
A monkeypox virus (MPXV) outbreak has been ongoing worldwide since May 2022. The role of specimens other than skin lesions for MPXV diagnosis is unknown. We evaluated 140 different clinical specimens ...by real-time PCR. The highest positivity rates (97%) were from skin lesions of any part of the body, followed by plasma, pharyngeal and anal swabs. Testing specimens from multiple sites may improve the sensitivity and reduce false-negative test results.
To analyze the association between patatin-like phospholipase domain-containing 3 gene (PNPLA3) rs738409 polymorphism and severity of liver disease in HIV/hepatitis C virus-coinfected patients.
We ...performed a cross-sectional study of 215 patients who underwent a liver biopsy. PNPLA3 rs738409 polymorphism was genotyped using GoldenGate assay. The outcome variables were as follows: advanced fibrosis (F ≥3 and FIB-4 ≥3.25), rapid fibrosis progression (FPR ≥0.10 fibrosis units/year), severe activity grade (A≥3), and steatosis (fatty hepatocytes ≥10%). The genetic association analysis was carried out according to an additive genetic model through logistic regressions adjusted by the most significant covariables.
Overall, 21.4% had F at least 3, 8.9% had FIB-4 at least 3.25, 11.4% had A at least 3, 60.6% had steatosis, and 32.5% had FPR at least 0.10. For each rs738409 G allele, we found an increased frequency of patients with advanced fibrosis (F at least 3) (0% CC, 18.5% CG, and 25.2% GG; P = 0.049) and FIB-4 at least 3.25 (0% CC, 3.8% CG, and 13.2% GG; P = 0.016). Furthermore, for each rs738409 G allele, the odds of having F at least 3 increased 2.15 times (95% confidence interval=1.07; 4.35; P = 0.029) and having FIB-4 at least 3.25 increased 8.77 times (95% of confidence interval = 1.11; 69.0; P = 0.039). Note that rs738409 G allele carriers tended to higher likelihood of having FPR at least 0.10, but statistical significance was not reached (P = 0.054). Finally, we did not find any association for A at least 3 and liver steatosis.
PNPLA3 rs738409 polymorphism was associated with the severity of liver fibrosis in patients coinfected with HIV and hepatitis C virus, suggesting that this polymorphism might also play a significant role in the progression of hepatic fibrosis in this group of patients.
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