Abstract
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.
•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.
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.
•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
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.
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.
Little evidence on coronavirus disease 2019 (COVID‐19) in people living with HIV (PLWH) is currently available. We reported clinical and viroimmunological data of all HIV‐positive patients admitted ...to our center with COVID‐19 from March 1 to May 12, 2020. Overall, five patients were included: all were virologically‐suppressed on antiretroviral therapy and CD4+ count was greater than 350 cell/mm3 in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA was never detected from nasopharyngeal swabs in two patients, whereas in the others, viral clearance occurred within a maximum of 43 days. Immunoglobulin G production was elicited in all patients and neutralizing antibodies in all but one patient. Specific‐T‐cell response developed in all patients but was stronger in those with the more severe presentations. Similarly, the highest level of proinflammatory cytokines was found in the only patient experiencing respiratory failure. Despite a mild presentation, patients with more pronounced immunosuppression showed high degrees of both cytokines production and immune activation. Our study did not find an increased risk and severity of COVID‐19 in PLWH. Adaptative cellular immune response to SARS‐CoV‐2 appeared to correlate to disease severity. The mild clinical picture showed in advanced HIV patients, despite a significant T‐cell activation and inflammatory profile, suggests a potential role of HIV‐driven immunological dysregulation in avoiding immune‐pathogenetic processes. However, other possible explanations, as a protective role of certain antiretroviral drugs, should be considered. Further larger studies are needed to better clarify the impact of HIV infection on COVID‐19.
Highlights
The clinical course of COVID‐19 and the dynamics of the immune response to SARS‐CoV‐2 infection in people living with HIV have not yet been fully elucidated Indeed, although worse outcomes might be expected in HIV‐positive patients compared to the general population, it has been supposed that the HIV‐related immune dysregulation could paradoxically mitigate the hyperinflammation syndrome responsible for the most severe complications of SARS‐CoV‐2 infection.
In this case series we did not find an increased risk of both acquiring and having a severe course of COVID‐19 in people living with HIV compared to how reported in the general population.
We observed that patients with more severe HIV‐related immunosuppression, despite the development of a specific immune response and the presence of a strong cellular immune‐activation and a moderate inflammatory profile, experienced a mild/moderate disease. These findings might suggest that the lower and impaired immune reactivity of advanced HIV infection could contribute to avoid immune‐pathogenetic processes. However, other possible explanations, as a potential protective role of certain antiretroviral regimens, should be considered.
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