Twenty-one pediatric liver transplant recipients were enrolled in a study comparing prophylaxis followed by preemptive therapy (10 patients) versus preemptive therapy alone (11 patients) for ...prevention of human cytomegalovirus (HCMV) disease. In the prophylaxis arm, patients were treated with ganciclovir for 30 days, then preemptive therapy was initiated with virologic monitoring for pp65 antigenemia. In the preemptive therapy arm, patients were treated on reaching 100,000 DNA copies/mL whole blood. An interim analysis showed that, although numbers of both infected and treated patients were comparable in the two arms, the median number of total days of antiviral therapy per patient (30 vs. 18, P<0.01) was significantly higher in the prophylaxis arm. No case of HCMV disease occurred in either arm. Therefore, the trial was interrupted and prophylaxis replaced with preemptive therapy alone. In parallel, the development of T-cell-mediated immune response was found to be comparable in both arms.
Information about severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in HIV‐infected individuals is scarce. In this prospective study, we included HIV (human immunodefeciency ...virus)‐infected individuals (people living with HIV PLWHIV) with confirmed SARS‐CoV‐2 infection and compared them with PLWHIV negative for SARS‐CoV‐2. We compared 55 cases of SARS‐CoV‐2 infection with 69 asymptomatic PLWHIV negative for SARS‐CoV‐2 reverse transcription‐polymerase chain reaction and/or serology. There was no significant difference between SARS‐CoV‐2 positive or negative patients for age distribution, gender, time with HIV infection, nadir CD4‐cell counts, type and number of co‐morbidities, current CD4 and CD8 counts and type of anti‐HIV therapy. Positive patients presented with a median of three symptoms (interquartile range, 1‐3). Most common symptoms were fever (76%), dyspnea (35%), anosmia (29%) non‐productive cough (27%), fatigue 22%), and ageusia (20%). Ten patients (18%) were completely asymptomatic. Four (7.2%) subjects died of coronavirus disease 2019. Factors significantly (P < .05) associated with death included age and number of co‐morbidities, while time from HIV infection and lower current CD4 counts were significant only in univariate analysis. HIV‐infected individuals are not protected from SARS‐CoV‐2 infection or have a lower risk of severe disease. Indeed, those with low CD4 cell counts might have worse outcomes. Infection is asymptomatic in a large proportion of subjects and this is relevant for epidemiological studies.
Highlights
This study addresses the question if specific characteristics of HIV infection may raise the risk of SARS‐CoV‐2 infection by comparing infected persons living with HIV (PLWHIV), either symptomatic or not, with other PLWHIV who tested negative for SARS‐CoV‐2 infection. None of the parameters classically used to define immune suppression or risk of immune impairment in HIV positive subjects does correlate with the risk of acquiring SARS‐CoV‐2 infection. Although low CD4 counts were not associated with the positivity for SARS‐CoV‐2, relative immunosuppression did seem to affect disease severity, and it might be associated with adverse outcomes. By contrast, there was no evidence that any specific antiretroviral drug affected SARS‐CoV‐2 infection or COVID‐19 severity.
The disease may cover a vast range of clinical pictures, being almost one fifth of infected individuals asymptomatic and variables already described for the general population as risk factors for a more severe disease such as advanced age and the presence of multiple co‐morbidities do apply to PLWHIV, too.
HIV‐infected individuals should not be considered protected from SARS‐CoV‐2 infection or as having lower risk of severe disease. Indeed, those with low CD4 cell counts might have worse outcomes than individuals with restored immunity. Infection may be asymptomatic in a large proportion of subjects and this variable must be counted when epidemiological studies are implemented in PLWHIV.
Control HIV replication requires continuous combined antiretroviral therapy (cART) as discontinuation of cART results in a rapid viral rebound. However, a few individuals exist who took cART for ...several years and did not show the expected viral rebound after treatment cessation. Most post-treatment controllers (PTCs) are early treated individuals. We report three cases who started cART during chronic infection.
Patients were treated and monitored according to Italian guidelines. For the description of cases, the percentage of CD8CD38HLA*DR cells, CD8CD38HLA*DR cells, major histocompatibility complex genotyping, total HIV-DNA and plasma levels of anti-retroviral (ARV) drugs were performed.
Patients started therapy during chronic infection. Patient 26636 started her first ARV drug two years after diagnosis and patients 93016 and 50293 started cART with high viral loads and low CD4 cell counts. Time without cART was 13, 11 and 1.5 years, respectively. None presented any of the protective class I HLA alleles and patient 93016 has the HLA-B*35 allele that appears to be enriched in PTCs. Patients 93016 and 50293 had very low levels of CD8CD38HLA*DR cells (<5%) much lower than those of patient 26636 (27%). T-cell-associated HIV-DNA was 3.78, 3.48 and 3.13 log copies/10 CD4, respectively.
Patients like ours may advance our understanding of the characteristics for which individuals may be more likely to achieve ART-free remissions. Furthermore, our patients are among the few so far described who started cART during chronic infection extending the hope that a functional cure is possible even in this setting.
Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in ...virologically suppressed patients.
In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART.
Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10).
Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms.
Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials.
HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. ...However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.
We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.
The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.
GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.
The aim of the study was to assess changes in clinical phenotype, and identify determinants of outcome in children with chronic hepatitis B virus (HBV) infection born in HBV-endemic countries ...followed in 2 Italian tertiary care centers after immigration or adoption.
A prospective observational study on hepatitis B e-antibodies-negative chronic hepatitis B children started on 2002. Patients with liver fibrosis, or those needing antiviral treatment were excluded. Immune active patients were defined those with raised transaminases (alanine aminotransferase > 40 IU/L), immune tolerants those having normal alanine aminotransferase, both exhibiting substantial viral replication (HBV DNA >2000 IU/mL).
Sixty-nine patients (44 boys, median age 4.7 years) had a median follow-up of 53 months. At entry, 18 (26%) children were immune tolerant, 47 (68%) immune active, and 4 had indeterminant immune status. At last follow-up, 14 (78%) of the immune-tolerant patients remained so, whereas only 23 (49%) of the immune active children maintained their initial immune phenotype. Seroconversion to hepatitis B e antibodies (SCHBe) occurred in only 2 (11%) immune tolerants, whereas 13 (28%) immune active patients achieved SCHBe.Ethnicity was the only feature independently correlated to SCHBe: Asian origin reduced by 4.1 times the probability of SCHBe (Asian vs other; odds ratio = 0.24 95% confidence interval = 0.07-0.76; P = 0.016) compared to other ethnicities, whereas viral genotype did not influence the outcome.
Ethnicity and immune status phenotype against HBV, rather than HBV genotype, are the main determinants of SCHBe in foreign-born children with chronic HBV infection.
The aim of the present study was to evaluate the virological response to a new antiretroviral treatment (ART2) after failure of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two ...nucleoside reverse transcriptase inhibitors (NRTIs)-containing regimen.
Retrospective observational study based on the Italian ARCA cohort database. Adult patients were included if they had a virological failure (defined as plasma viral load above 500 copies/ml in two subsequent visits) while on a treatment with one NNRTI plus 2 NRTIs, had an available HIV genotype.
Patients on ART2 were followed up for 791 person/year and median follow up was 10.8 months(IQR 5.2-26). Variables associated with reduced risk of ART2 virological failure at univariable analysis had started the treatment in recent years (HR 0.90; 95% CI 0.86-0.94, p < 0.0001) and duration of previous NNRTI treatment (HR 0.995; 95%CI 0.990-0.990, p=0.045). Variables associated with increased risk of virological failure of ART2 were a higher plasma viral load (pVL) at baseline(HR 1.2; 95% CI 1.07-1.34, p=0.002) and the type of treatment, in particular an unboosted PI-containing regimen vs. a boosted PI-containing regimen(HR 1.6; 95%CI 1.25-2.04 p < 0.0001) and a non-PI-containing vs. a boosted PI-containing regimen (HR 1.56; 95% CI 1.25-1.96, p < 0.0001). At multivariable analysis, year of ART2 start, pVL at NNRTI failure as well as using a boosted PI remained statistically significant predictors.
This study highlights the role of drugs with high genetic barrier, such as boosted PI as a cornerstone to build a new antiretroviral treatment in patients failing a NNRTI based regimen.
Existing evidence about HIV and SARS-CoV-2 co-infection has, so far, yield conflicting results. Methods: This is a cohort, single center, clinical study aimed at identifying possible characteristics ...of PLWH that could correlate with the risk of acquiring SARS-CoV-2 and would influence the outcome. 155 cases of SARS-CoV-2 infection were compared with 307 PLWH who tested negative. No variable was associated with an increased risk of infection. SARS-CoV-2 PLWH were completely asymptomatic in 20.6% of cases. Factors associated with severe COVID-19 were age (P=0.001), diabetes (P=0.009) hypertension (P=0.004), cardiovascular disease (P=0.001) or an increasing number of chronic co-morbidities (P=0.002); only the first two variables retained statistical significance in a multivariable model. Only older age and a lower CD4 count were statistically associated with death in the multivariate model. Sixteen PLWH not included in the analysis were infected by SARS-Cov-2 after vaccination. In 4 cases the infection was completely asymptomatic, while in the remaining 12 cases the infection was mild and resembled a flu-like syndrome. Conclusions: No baseline characteristic defines patients at greater risk of SARS-CoV-2 infection. Older age and the presence of multi-comorbidities are risk factors for a severe clinical course. Lower CD4 counts correlate with a fatal outcome.
PDF
