Investigating coping and stigma in people living with HIV through narrative medicine in the Italian multicentre non-interventional study DIAMANTE.

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping.

Temporal trend of drug-resistance and APOBEC editing in PBMC genotypic resistance tests from HIV-1 infected virologically suppressed individuals.

BACKGROUND: We aimed at evaluating the temporal trend of drug-resistance and APOBEC editing from HIV-DNA genotypic resistance tests (GRT) in virologically suppressed individuals. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Human immunodeficiency virus (HIV) and coronavirus disease 2019; impact on vulnerable populations and harnessing lessons learnt from HIV programmes.

Coronavirus disease 2019 (COVID-19) can act as a dual prong attack against management of people living with human immunodeficiency virus (HIV); it induces harm on both individual and national levels. People living with HIV may show rapid deterioration in severe acute respiratory syndrome coronavirus 2 infection as a result of physiological or psychological vulnerability. Additionally, the spread of COVID-19-especially in low- and middle-income countries-may limit HIV control measures, delivery and linkage to HIV care and prevention. Attention should be given to pregnant women and the LGBTQI+ community for their higher susceptibility to poor outcomes. Engagement of both governmental and non-governmental organizations is encouraged for better results.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide or dual therapy-based regimens in HIV-infected individuals with viral load ≤50 copies/mL: does estimated glomerular filtration rate matter?

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.

SARS-CoV-2 infection does not induce HIV viral escape in the central nervous system: A case series.

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.

HIV MDR is still a relevant issue despite its dramatic drop over the years.

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.

Liver stiffness reduction and serum fibrosis score improvement in HIV/hepatitis C virus-coinfected patients treated with direct-acting antivirals.

OBJECTIVES: Only a few studies have addressed liver stiffness dynamics after hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim was to evaluate the variation in liver stiffness and in serum liver fibrosis scores in HIV/HCV-coinfected patients before and after treatment with direct-acting antivirals (DAAs). METHODS: Liver stiffness measured using transient elastography as well as serum liver fibrosis scores [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were evaluated before and at 6-12 months after DAA treatment. Variation in the outcome variables was evaluated using the Wilcoxon nonparametric test. Univariate analysis and multivariate regression models were used. RESULTS: A total of 78 HIV/HCV-coinfected subjects were included in the study. Median values of hepatic stiffness significantly decreased after DAA treatment compared with baseline [16.8 (interquartile range (IQR) 10.2-27.0) kPa at baseline vs. 9.4 (IQR 6.7-15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB-4 score [2.8 (IQR 1.5-4.8) vs. 2.0 (IQR 1.3-3.2), respectively; P < 0.01] and APRI [0.9 (IQR 0.5-2.2) vs. 0.4 (IQR 0.2-0.7), respectively; P < 0.01] was found. In univariate analysis, liver stiffness decrease was associated with increasing age, 'other' HCV genotype (vs. G1), the presence of cirrhosis, higher pre-DAA liver stiffness, sofosbuvir-based regimens and longer DAA treatment (all P < 0.05). Multivariate regression confirmed the significance of the association only with higher baseline liver stiffness (P < 0.01). Greater FIB-4 and APRI reductions were associated with higher respective baseline values, while the presence of hepatic steatosis correlated with lower score reduction after DAA. CONCLUSIONS: A reduction in liver stiffness and an improvement in fibrosis scores were observed in HIV/HCV-coinfected patients soon after DAA treatment. The clinical implications of these observations need to be evaluated in larger populations with longer follow-up.

Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000-14.

Background: Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. Methods: In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Results: Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P < 0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P = 0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P = 0.047]. Conclusions: The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.

Listeria meningoencephalitis and anti-GQ1b antibody syndrome.

We report the first case of Listeria monocytogenes meningoencephalitis associated with anti-GQ1b antibody syndrome in an immunocompetent adult. A prompt diagnosis, made thanks to the multidisciplinary contribution, allowed a combined therapeutic approach leading to final favourable outcome, despite several intercurrent complications.