•The impact of co-infection with SARS-CoV-2 on HIV replication in the central nervous system (CNS) is unknown.•SARS-CoV-2 could alter the permeability of the blood–brain barrier and cause a CNS HIV ...escape.•The few symptoms during coronavirus disease 2019 (COVID-19) suggest a contained inflammatory response in CNS/plasma.•Poor immunological recovery might contribute to soften immune-pathogenetic processes.
We report two cases of HIV positive patients with SARS-CoV-2 infection and a recent diagnosis of opportunistic infections of central nervous system (CNS). We investigated the potential impact of coinfection with SARS-CoV-2 on HIV replication in CNS.
Objectives
We evaluated the efficacy and tolerability of lamivudine + dolutegravir in a cohort of HIV‐1 infected, treatment‐experienced patients with undetectable HIV‐RNA.
Methods
Time to treatment ...discontinuation (TD) and virological failure (VF) and their predictors were assessed in a multicenter cohort of HIV‐1 infected patients, starting lamivudine + dolutegravir after reaching viral suppression. Secondary objective was the evaluation of changes in lipid profile, renal and immunological functions at week 48.
Results
We enrolled 206 patients (72.8% male, with 51 years median age), who mainly switched their antiretroviral therapy for simplification (32.5%) or drug toxicity (54.5%). The estimated probability of maintaining virological suppression at 48 and 96 weeks was 98.2% and 95.1%, respectively. VF was independently predicted by cumulative time on antiretroviral therapy. The estimated probability of remaining on lamivudine plus dolutegravir was 86.7% and 80.5% at week 48 and 96, respectively. A significant improvement in immunological function (CD4 count and CD4/CD8 ratio) was evidenced at week 48, as well as a decrease in total cholesterol/HDL ratio, triglycerides and estimated glomerular filtration rate.
Conclusions
Lamivudine plus dolutegravir was effective in maintaining viral suppression in our cohort and led to an improvement in metabolic and immunologic functions.
Evidences on the absence of risk of sexual transmission of HIV by persons living with HIV/AIDS (PLWHA) with undetectable plasma HIV-RNA (HIV-RNA <200 copies/ml) led to the worldwide campaign "U = U" ...(undetectable = untransmittable). The purpose of this study was to evaluate the perceived accuracy of this message among PLWHA, HIV-negative people having unprotected sex (PHUS) and infectious diseases' (ID) physicians in Italy. A nationwide survey has been conducted using three different anonymous questionnaires (for ID physicians, PLWHA and PHUS). A total of 1121 participants filled the questionnaires: 397 PLWHA; 90 physicians; 634 PHUS. Awareness of U = U message has been reported in 74%, 92% and 47% of PLWHA, ID physicians and PHUS, respectively. The perception of accuracy of the U = U message among those aware was reported as high in 80.4%, 79.5% and 67.3% of PLWHA, ID physicians and PHUS, respectively. Physicians perceived that 11% of PLWHA have a high rate of perception of U = U, whereas among PLWHA, only 34% reported definitive positive messages from physicians. Discrepancies between awareness and perception of accuracy of the message U = U in PLWHA and physicians have been found, suggesting still low confidence in the community regarding the message itself.
•In the last decade, resistance in HIV-DNA was 35% in Italy.•Resistance in HIV-DNA was stable over the period 2010-2021.•Complex treatment history was associated with resistance in HIV-DNA.•APOBEC ...editing was found in around one quarter of HIV-DNA sequences.
We aimed at evaluating the temporal trend of drug-resistance and APOBEC editing from HIV-DNA genotypic resistance tests (GRT) in virologically suppressed individuals.
Major resistance mutations (MRM), genotypic susceptibility score (GSS) for the current regimen and APOBEC-related mutations (APO-M) were evaluated. Potential changes in trends of MRM and APO-M over-time were assessed and predictors of MRM detection or sub-optimal GSS (GSS<2) at HIV-DNA-GRT were estimated through logistic regression analyses.
Among the 1126 individuals included, 396 (35.2%) harboured at least one MRM (23.4% to NRTI, 18.8% to NNRTI, 7.7% to PI and 1.4% to INSTI N=724); 132 (12.3%) individuals showed a GSS <2. APO-M and stop codons were found in 229 (20.3%) and 105 (9.3%) individuals, respectively. APO-DRMs were found in 16.8% of individuals and were more likely observed in those individuals with stop codons (40.0%) compared to those without (14.4%, P<0.001). From 2010 to 2021 no significant changes of resistance or APO-M were found. Positive predictors of MRM detection at HIV-DNA GRT were drug abuse, subtype B infection, and a prolonged and complex treatment history. Perinatal infection and having at least 2 stop codons were associated with a current suboptimal regimen.
In virologically suppressed individuals, resistance in HIV-DNA and the extent of APOBEC editing were generally stable in the last decade. A careful evaluation of APOBEC editing might be helpful to improve the reliability of HIV-DNA GRT. Further investigations are required to understand how to apply the estimation of APOBEC editing in refining genotypic evaluation.
Abstract
Objectives
To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.
Methods
...Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).
Results
Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance.
Conclusions
A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.
•Switching from tenofovir disoproxil fumarate (TDF)-containing regimens has increased considerably in recent years.•A high proportion of people with a controlled viral load switched from TDF to ...tenofovir alafenamide (TAF).•Only 3.5% of patients switched from TDF to a dual therapy (DT) regimen.•Low eGFR was associated with a higher risk of switching to DT but not to TAF-based cART.
Our aim was to evaluate the association between recent eGFR values and risk of switching from TDF to TAF or dual therapy (DT) in real life. HIV-positive patients achieving HIV-RNA ≤50 copies/mL for the first time after starting a TDF-based regimen were included. Kaplan–Meier (KM) curves and Cox regression models were used to estimate the time from TDF to switch to TAF or DT. 1486 participants were included: median (IQR) age 36 (30–42) years; baseline CKD-EPI eGFR 99.92 (86.47–111.4) mL/min/1.73m2. We observed a consistently higher proportion of people with HIV-RNA ≤50 copies/mL who switched from TDF to TAF rather than to DT. By competing risk analysis, at 2 years from baseline, the probability of switching was 3.5% (95% CI 2.6–4.7%) to DT and 46.7% (42.8–48.5%) to TAF. A significantly higher probability of switching to TAF was found for patients receiving INSTI at baseline versus NNRTIs and PI/b KM, 65.6% (61.7–69.4%) vs. 4.0% (1.8–6.1%) and 59.9% (52.7–67.2%), respectively; P < 0.0001. eGFR <60 mL/min/1.73m2 both as time-fixed covariate at baseline or as current value was associated with a higher risk of switching to DT aHR 6.68 (2.69–16.60) and 8.18 (3.54–18.90); P < 0.001 but not to TAF-based cART aHR 0.94 (0.39–2.31), P = 0.897; and 1.19 (0.60–2.38), P = 0.617. Counter to our original hypothesis, current eGFR is used by clinicians to guide switches to DT but does not appear to be a key determinant for switching to TAF.
Objectives
Italy is a low‐incidence region for hepatitis A; however, during the last 2 years an increase in the incidence of hepatitis A virus (HAV) infection was reported in Europe. The aim of this ...study was to describe this recent outbreak.
Methods
We retrospectively analysed all cases of acute hepatitis A diagnosed at our laboratory between January 2010 and June 2017. We evaluated the following variables at the time of diagnosis: sex, age, nationality, glutamic oxaloacetic transaminase (GOT/AST), glutamic pyruvic transaminase (GPT/ALT), bilirubin concentration, international normalized ratio (INR) and the presence or absence of anti‐HIV‐1/2 antibodies. Hospitalization was also considered. We analysed these parameters using the χ2 test and Mann–Whitney U‐test.
Results
A total of 225 cases were analysed; 82.7% were in male patients, 94.2% were in Italians and the median age of the patients was 36.4 years. At diagnosis, the median GOT value was 306 U/L, the median GPT was 1389 U/L, and the median total bilirubin value was 5.88 mg/dL. Hospitalization was required for 142 patients, with a median duration of hospital stay of 8.5 days. In 2016‐2017 we registered 141 cases, with a higher prevalence of male patients, higher GPT values and a higher prevalence of patients aged 20‐39 years compared with older (2010‐2015) cases. Homosexual intercourse was reported as the HAV risk factor in 70.2% of patients. HIV serology was available for 120 patients: 24 were HIV‐positive, four of whom represented new diagnoses. HIV‐positive patients showed lower bilirubin and GPT values and fewer hospitalizations than HIV‐negative patients.
Conclusions
In 2016–2017, we saw a rise in the number of hepatitis A cases, with a higher prevalence of adult male patients. No significant differences regarding the prevalence of HIV coinfection emerged.
AtLaS was a single-arm pilot study that demonstrated promising efficacy and safety of treatment simplification to a dual regimen with atazanavir/ritonavir + lamivudine in virologically suppressed ...HIV-positive patients. Here, we report data from the 144 week follow-up.
At baseline, patients treated with a three-drug atazanavir/ritonavir-based regimen were switched to 300/100 mg of atazanavir/ritonavir plus 300 mg of lamivudine once daily. Major clinical events, laboratory parameters, neurocognitive performance, bone composition and body fat distribution were monitored. Treatment failure was defined as a discontinuation/switch of the regimen or virological failure (HIV-RNA >50 copies/mL in two consecutive determinations or a single level above 1000 copies/mL).
After 144 weeks, 9/40 (22.5%) treatment failures occurred, including two virological failures (Weeks 48 and 53, without resistance). A significant increase in the CD4 count was observed at Week 96 (+124 cells/mm(3); P = 0.002) and Week 144 (+94 cells/mm(3); P = 0.008). After 144 weeks, a significant increase in total cholesterol (+25 mg/dL; P = 0.001), HDL cholesterol (+6 mg/dL; P = 0.024) and LDL cholesterol (+12 mg/dL; P = 0.008) was observed, without any change in triglyceride levels, total cholesterol/HDL ratio or LDL/HDL ratio. A significant increase in the estimated glomerular filtration rate (+25 mL/min/1.73 m(2); P < 0.001) and lumbar spine T-score and Z-score (+0.2, P = 0.011; and +0.35, P = 0.001, respectively) and a decrease in trunk fat (-1.898 g; P = 0.005) were also observed. Neurocognitive function did not decline over time. Concerning safety, 10 moderate to severe adverse events were recorded in eight patients; overall seven cases of renal colic (possibly treatment related) were observed, leading to a discontinuation of treatment in two patients.
Data from the 144 week follow-up suggested good long-term efficacy of the simplification strategy that was investigated, with rare virological failure and a potential for improvement of the CD4 count, renal function and bone mineral density. This strategy warrants further investigation in a randomized trial.
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