Background. The risk of liver toxicity during antiretroviral drug use in human immunodeficiency virus (HIV)-positive patients increases in the presence of chronic hepatitis C virus (HCV) infection. It is unknown whether sustained HCV clearance after interferon (IFN)-based therapy might reduce this complication. Methods. The incidence of severe elevations in liver enzyme levels during antiretroviral therapy was retrospectively analyzed in a group of HIV/HCV-coinfected patients after completion of a full course of IFN-based therapy. Hepatic events were recorded according to the achievement of a sustained virological response (SVR), and the presence of advanced liver fibrosis was assessed by transient elastometry. Results. A total of 132 HIV/HCV-coinfected patients were analyzed (66% men; mean age, 38 years). Overall, 33% achieved an SVR and 40% had advanced liver fibrosis after IFN therapy. A total of 49 episodes of liver toxicity occurred during a mean of 35 months of follow-up (9.7% per year) after IFN therapy. The yearly incidence of hepatic events was greater in patients who did not achieve an SVR than in those who did (12.9% vs. 3.1%; P < .001) and in patients with advanced liver fibrosis than in those without it (14.4% vs. 7.6%; P = .003). Drugs involved in hepatic events were dydeoxynucleoside analogues (namely, didanosine and stavudine; 40%) nevirapine (30%), efavirenz (11%), and protease inhibitors (PIs; 8%). In logistic regression analysis, lack of an SVR (odds ratio [OR], 6.13 [95% confidence interval {CI}, 1.83–37.45]; P = .003) and the use of dydeoxynucleosides (OR, 3.59 [95% CI, 1.23–10.42]; P = .02) were independent predictors of hepatotoxicity after IFN therapy. Conversely, regimens containing PIs (OR, 0.07 [95% CI, 0.02–0.30]; P < .01) or efavirenz (OR, 0.13 [95% CI, 0.04–0.44]; P = .001) were associated with a diminished risk of hepatic events. Conclusion. Sustained HCV clearance after IFN-based therapy reduces the risk of liver toxicity during antiretroviral therapy, which should further encourage the treatment of chronic hepatitis C in HIV-coinfected patients. In this population, prescription of PIs or efavirenz decreases and use of dydeoxynucleoside analogues increases the risk of hepatotoxicity.
Background. Single-nucleotide polymorphisms (SNPs) near the IL28B gene have recently been associated with spontaneous hepatitis C virus (HCV) clearance and response to interferon-based therapies in patients with chronic hepatitis C. Because human immunodeficiency virus (HIV) coinfection appears to accelerate HCV-related liver fibrosis progression, any influence of IL28B SNP on the risk of developing cirrhosis might be more easily recognized in the coinfected population. Methods. All HIV-HCV–coinfected patients who underwent hepatic elastography before initiating a course of pegylated interferon plus ribavirin therapy at 2 Spanish clinics were retrospectively identified. Liver cirrhosis was defined as >14.5 kPa by transient elastography. The IL28B rs12979860 SNP was examined in a blinded fashion. Results. A total of 304 HIV-HCV–coinfected individuals were analyzed (mean age, 43 years; 80% were male; and 85% were receiving antiretroviral therapy), of whom 18% had cirrhosis. IL28B genotype distribution was as follows: CC, 46%; CT, 43%; and TT, 11%. Cirrhosis was more frequent in CC than CT/TT carriers (24% vs 13%; P = .01). Logistic regression analysis revealed that older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.99–1.12]; P = .08), past alcohol abuse (OR, 1.97; 95% CI, 0.95–4.06; P = .07), and CC IL28B genotype (OR, 2.32; 95% CI, 1.22–4.41; P = .01) were predictors of cirrhosis. Interestingly, mean (SD) alanine aminotransferase (ALT) levels were greater (90 ± 53 vs 71 ± 33 IU/L;, P = .01) in IL28B CC than CT/TT carriers during the prior 4.8 ± 3.8 years. Conclusions. The IL28B rs12979860 CC genotype is associated with a higher prevalence of cirrhosis in HIV-HCV–coinfected patients than CT/TT genotypes, suggesting that IL28B CC carriers may experience a more rapid progression of HCV-related liver fibrosis, perhaps as result of increased liver inflammation. Thus, access to HCV treatment is of utmost importance in IL28B CC carriers, in whom treatment response is better and in whom progression to cirrhosis might occur more rapidly.
The remarkable reduction in HIV-related morbidity and mortality as a consequence of the widespread use of highly active antiretroviral therapy (HAART) has led to a growing number of HIV-infected persons and their partners requesting counselling regarding the chances of reproduction. A thoughtful medical evaluation of the couple, which should entail HIV status, screening for genital infections and fertile potential, is needed before considering any reproductive attempt. Given that both sexual and perinatal transmission of HIV is directly correlated with the level of viral replication, being almost negligible in patients with undetectable viremia, HAART should be given to the infected partner to minimize the risk of transmission. Assisted reproduction after ‘sperm washing' may further reduce the chances of infection, although this is not within reach or desire for a significant number of HIV-serodiscordant couples. From our perspective, natural conception could now be considered a possible alternative for HIV-serodiscordant couples, as long as complete suppression of viremia with HAART is achieved in the infected partner. The objective of this paper is to propose a protocol that may minimize risks in HIV-discordant couples that have opted for natural conception.
Assessment of T-cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens may be of value to determine long-lasting protection to breakthrough infections or reinfections. Interferon gamma release assay is a validated method to test cellular immunity in mycobacterial infections and has been proposed for patients with SARS-CoV-2 infection or vaccination.
Nursing homes for older adults have concentrated large numbers of severe cases and deaths for coronavirus disease 2019 (COVID-19). Point seroprevalence study of nursing homes to describe the demography and characteristic of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG)-positive residents and staff. Clinical information and blood samples were available for 9,332 residents (mean age 86.7 ± 8.1 years, 76.4% women) and 10,614 staff (mean age 45.6 ± 11.5, 86.2% women). Up to 84.4% of residents had frailty, 84.9% co-morbidity and 69.3% cognitive impairment; 65.2% of workers were health-aides. COVID-19 seroprevalence was 55.4% (95% confidence interval (CI), 54.4–56.4) for older adults and 31.5% (30.6–32.4) for staff. In multivariable analysis, frailty of residents was related with seropositivity (odds ratio (OR): 1.19, P = 0.02). In the case of staff, age > 50 years (2.10, P < 0.001), obesity (1.19, P = 0.01), being a health-aide (1.94, P < 0.001), working in a center with high seroprevalence in residents (3.49, P < 0.001) and contact with external cases of COVID-19 (1.52, P < 0.001) were factors associated with seropositivity. Past symptoms of COVID-19 were good predictors of seropositivity for residents (5.41, P < 0.001) and staff (2.52, P < 0.001). Level of dependency influences risk of COVID-19 among residents. Individual and work factors, contacts outside the nursing home are associated with COVID-19 exposure in staff members. It is key to strengthen control measures to prevent the introduction of COVID-19 into care facilities from the community.