A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo

Liver stiffness and virologic outcomes after introducing tenofovir as part of antiretroviral therapy in lamivudine-experienced adults with HIV and hepatitis B virus (HBV) co-infection in Ghana: four-year follow up of the prospective HEPIK cohort

Introduction Until recently lamivudine was the only available agent to treat hepatitis B in the context of HIV infection in sub‐Saharan Africa. Tenofovir is gradually becoming available although access remains far from universal. Long‐term outcomes of introducing tenofovir as part of antiretroviral therapy (ART) in subjects previously extensively exposed to lamivudine as the sole HBV‐active agent in the region are unknown. Methods We report from a prospective cohort of HIV/HBV co‐infected adults attending for HIV care in Kumasi, Ghana, where HBsAg prevalence is 14%. HBsAg‐positive subjects were invited to attend for transient elastography (TE) and blood sampling before the introduction of tenofovir (TO) as part of ART, and within 1 year (T1) and 4 years (T2) of starting tenofovir. Adherence and alcohol consumption were determined by a questionnaire‐based interview. Results Overall 178 patients underwent evaluation at T0/T1, of whom 98 (55%) also attended for assessment at T2. Remaining patients were lost to follow up (50; 28%); had died (10; 6%); declined to attend (17; 10%); or were excluded due to pregnancy (2; 1 %) or invalid TE (1; 1 %). Of the 98 subjects, 94 had started tenofovir‐based ART and had received tenofovir for median 4 years (IQR 3.8, 4.1), while continuing previous lamivudine (Table 1). By multivariable linear regression, female gender, no history of alcohol excess, and higher HBV DNA level, higher liver stiffness, and lower platelet count at T0/T1 were significant predictors of decreasing liver stiffness between TO/1 and T2. No treatment‐emergent resistance mutations in HBV polymerase were observed by Sanger sequencing among subjects with HBV DNA>100 lU/ml at T2; one subject showed M204V+V173L+L180M at both TO and T2. Conclusions This is the first report of the long‐term impact on liver stiffness and virologic parameters of introducing tenofovir as part of ART in extensively lamivudine exposed HIV/HBV co‐infected patients in sub‐Saharan Africa. Significant reductions in liver stiffness and improved HBV control were observed at four years

Outcomes of COVID-19 related hospitalization among people with HIV in the ISARIC WHO Clinical Characterization Protocol (UK): a prospective observational study

BACKGROUND: Evidence is conflicting about how HIV modulates COVID-19. We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the ISARIC WHO CCP study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, ten individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47,592 patients, 122 (0.26%) had confirmed HIV infection and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 versus 74 years; p<0.001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive vs. HIV-negative groups (26.7% vs. 32.1%; p=0.16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; p<0.001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; p=0.05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; p=0.008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; p<0.001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19

Detection of the NS3 Q80K polymorphism by Sanger and deep sequencing in hepatitis C virus genotype 1a strains in the UK

AbstractThe Q80K polymorphism in the hepatitis C virus (HCV) NS3 enzyme reduces susceptibility to simeprevir and other novel protease inhibitors. The aims of this study were to determine the prevalence of Q80K in treatment-naïve HCV-1a carriers in the North West region (NW) and South East region (SE) of England, investigate the occurrence of Q80K as a minority variant, and characterize viral phylogeny. Plasma samples from subjects who were naïve to anti-HCV therapy were subjected to conventional (Sanger) and deep (Illumina-Miseq, 1% interpretative cut-off) sequencing of NS3. Q80K occurred in 44 of 238 subjects (18.5%, 95% CI 13.6–23.4%), including 19 of 70 (27.1%) in the NW and 25 of 168 (14.9%) in the SE (p 0.0425), with no difference in HCV RNA load or human immunodeficiency virus (HIV) status. Q80K frequencies in reads of samples subjected to Illumina sequencing were >40% in all cases. Among subjects with Q80K, five of 44 (11.4%) showed one additional major resistance-associated mutation in NS3, detected at frequencies of >10% (V36L and V55A) or <10% (V36M). Phylogenetic analyses identified the two recognized HCV-1a lineages with (clade I) and without (clade II) Q80K. Overall, 148 of 238 (62.2%) sequences occurred within regional or inter-regional clusters, each comprising 3–20 sequences. There was no unique clustering of English sequences relative to strains from continental Europe and North America. In conclusion, Q80K was found at a high prevalence among treatment-naïve HCV-1a carriers in England, and was reliably detected by conventional sequencing, with no increased detection by deep sequencing. English sequences were highly interspersed with sequences from elsewhere in Europe (clade II) and North America (clade I), and their phylogeny was consistent with multiple introductions from different areas