HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets ...for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women's Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.
Effective antiretroviral (ARV) therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state ...pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP) concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold) at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%). We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits). Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3%)) and increased in higher quartiles (to 158/204 (77.5%) for quartile 4). The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001) those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.
Abstract
Background
It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or ...infections.
Methods
We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA).
Results
There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24–108 years; P = .001).
Conclusions
Despite antiretroviral therapy–associated improvement in CD4+ T-cell counts (nadir, <200/μL; >350/μL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.
Despite successful immune reconstitution after antiretroviral therapy, virus-specific CD4+ T-cell memory and antiviral antibody responses after childhood smallpox vaccination were found to be preferentially lost among women with human immunodeficiency virus (HIV) infection compared with matched HIV-uninfected controls.
Multi-drug resistance in the post COVID-19 world is a growing concern. The objective of this study was to describe temporal trends and explore independent risk factors for the isolation of multi-drug ...resistant (MDR) P. aeruginosa.
This was a retrospective case-control study of patients with P. aeruginosa isolates recovered from January 2019 to December 2020. MDR P. aeruginosa was defined as non-susceptibility to at least one agent in three or more anti-pseudomonal antimicrobial categories.
In total, 258 unique isolates were identified. Prolonged hospitalization (P<0.001), prior antibiotic use (P<0.001), and respiratory sources (P<0.001) were strongly associated with the presence of MDR P. aeruginosa. From 2019 to 2020, there was a decrease in the total number of P. aeruginosa isolates but a significant increase in the proportion of MDR P. aeruginosa isolates (P=0.015).
Over a period that coincided with the COVID-19 pandemic, there was an increased proportion of MDR P. aeruginosa isolates from hospitalized patients. Improved identification of patients at risk for MDR P. aeruginosa could facilitate appropriate empiric antibiotic decisions like dual anti-pseudomonal therapy. The features of the COVID-19 outbreak that had a severe impact on patient care and that may have affected drug resistance in other respiratory pathogens should be explored.
In 2015, Clostridium difficile testing rates among 30 US community, multispecialty, and cancer hospitals were 14.0, 16.3, and 33.9/1,000 patient-days, respectively. Pooled hospital onset rates were ...0.56, 0.84, and 1.57/1,000 patient-days, respectively. Higher testing rates may artificially inflate reported rates of C. difficile infection. C. difficile surveillance should consider testing frequency.
After a precipitous increase in the incidence of infectious syphilis in the United States during the late 1980s and early 1990s, the rate of new cases has declined so dramatically that a program ...initiated by the Centers for Disease Control and Prevention (CDC) to achieve elimination appears to stand a good chance of succeeding. In the fall of 2000, the CDC convened an advisory group to examine the recent medical literature regarding syphilis treatment. Published literature in peer-reviewed journals and abstracts from relevant scientific meetings that have appeared since the last STD Treatment Guidelines meeting in 1997 were reviewed. Where applicable, unpublished data from studies in progress were also discussed. Expert opinion was sought. Through all these efforts, it appears that the azalide azithromycin and the third-generation cephalosporin ceftriaxone should find more definitive roles in the treatment of syphilis. None will eclipse the continued primacy of penicillin for this purpose.
We sought to assess the effectiveness of approaches targeting improved sexually transmitted infection (STI) sexual partner notification through patient referral.
From January 2002 through December ...2004, 600 patients with Neisseria gonorrhoeae or Chlamydia trachomatis were recruited from STI clinics and randomly assigned to either a standard-of-care group or a group that was counseled at the time of diagnosis and given additional follow-up contact. Participants completed an interview at baseline, 1 month, and 6 months and were checked at 6 months for gonorrhea or chlamydial infection via nucleic acid amplification testing of urine.
Program participants were more likely to report sexual partner notification at 1 month (86% control, 92% intervention; adjusted odds ratio AOR = 1.8; 95% confidence interval CI = 1.02, 3.0) and were more likely to report no unprotected sexual intercourse at 6 months (38% control, 48% intervention; AOR = 1.5; 95% CI = 1.1, 2.1). Gonorrhea or chlamydial infection was detected in 6% of intervention and 11% of control participants at follow-up (AOR = 2.2; 95% CI = 1.1, 4.1), with greatest benefits seen among men (for gender interaction, P = .03).
This patient-based sexual partner notification program can help reduce risks for subsequent STIs among urban, minority patients presenting for care at STI clinics.
To identify factors that affect normalization of laboratory measures after treatment for neurosyphilis, 59 subjects with neurosyphilis underwent repeated lumbar punctures and venipunctures after ...completion of therapy. The median duration of follow-up was 6.9 months. Stepwise Cox regression models were used to determine the influence of clinical and laboratory features on normalization of cerebrospinal fluid (CSF), white blood cells (WBCs), CSF protein concentration, CSF Venereal Disease Research Laboratory (VDRL) reactivity, and serum rapid plasma reagin (RPR) titer. Human immunodeficiency virus (HIV)—infected subjects were 2.5 times less likely to normalize CSF-VDRL reactivity than were HIV-uninfected subjects. HIV-infected subjects with peripheral blood CD4+ T cell counts of ⩽200 cells/µL were 3.7 times less likely to normalize CSF-VDRL reactivity than were those with CD4+ T cell counts of >200 cells/µL. CSF WBC count and serum RPR reactivity were more likely to normalize but CSF-VDRL reactivity was less likely to normalize with higher baseline values. Future studies should address whether more intensive therapy for neurosyphilis is warranted in HIV-infected individuals.
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