Lipids and transaminase elevations in ARV-experienced PLWH switching to a doravirine-based regimen from rilpivirine or other regimens.

BACKGROUND: Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. METHODS: We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. RESULTS: In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. CONCLUSIONS: PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF.

Metabolic syndrome and body weight in people living with HIV infection: analysis of differences observed in three different cohort studies over a decade.

OBJECTIVES: The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross-sectional studies conducted over three different periods: 2005, 2011 and 2015. METHODS: This was a multi-centre, nationwide study. Data were collected in three studies from the CISAI group - SIMOne, HIV-HY and STOPSHIV - and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. RESULTS: Overall, the mean age was 46.9 ± 10.2 years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52-0.78) in 2011 and 0.56 (95% CI: 0.46-0.69) in 2015 compared with 2005, while BMI (kg/m2 ) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p < 0.0001). CONCLUSIONS: In recent years, PHIV have had a significantly improved metabolic profile compared with previously, despite increasing weight and BMI.

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

BACKGROUND: In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). METHODS: To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years). RESULTS: In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex. CONCLUSIONS: Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age.

In vitro susceptibility to fostemsavir is not affected by long-term exposure to antiviral therapy in MDR HIV-1-infected patients.

OBJECTIVES: Fostemsavir is the prodrug of the HIV-1 attachment inhibitor temsavir and is currently under clinical assessment in heavily treatment-experienced patients with limited therapeutic options. We evaluated the genotypic and phenotypic susceptibility to temsavir in a panel of samples collected from patients harbouring MDR strains enrolled in the Italian PRESTIGIO Registry. METHODS: Plasma samples from 24 patients were used for HIV-1 gp120 sequencing, while viral tropism and susceptibility to temsavir were assessed through a homemade phenotypic assay with pseudotyped viruses expressing patient-derived Env protein. RESULTS: Of the 24 patients enrolled, 18 (75%) were male, median (IQR) age was 55 years (52-61), time since HIV-1 diagnosis was 27 years (24-30), time on ART was 26 years (23-27) and 11 (46%) had a previous AIDS diagnosis. Exposure to entry inhibitors (maraviroc and/or enfuvirtide) had occurred in 19 (79%) patients. Among 23/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). Pseudotyped viruses were obtained from 23/24 samples and viral tropism was CXCR4-tropic, CCR5-tropic and dual/mixed-tropic in six, nine and eight cases, respectively. Phenotypic susceptibility to temsavir was comparable to the reference WT viruses NL4-3 and AD8 in all samples, irrespective of RAMs. Viral tropism and exposure to entry inhibitors did not impact temsavir susceptibility. CONCLUSIONS: These data support the use of fostemsavir as a valuable therapy option in patients harbouring MDR virus. The role of laboratory testing in optimal screening of patients eligible for fostemsavir treatment remains to be investigated.

Smoking habits in HIV-infected people compared with the general population in Italy: a cross-sectional study.

BACKGROUND: Tobacco use is a leading cause of preventable diseases and death for all individuals, even more so for people living with HIV (PLWH), due to their status of chronic inflammation. To date, in Italy no study was performed to compare smoking habits in PLWH and the general population. We aimed to investigate smoking habits in PLWH, as compared to the general population. METHODS: Multi-center cross-sectional study. Smoking habits were compared between PLWH and the general population. PLWH were enrolled in the STOPSHIV Study. The comparison group from the general population was derived from a survey performed by the National Statistics Institute (ISTAT), with a stratified random sampling procedure matching 2:1 general population subjects with PLWH by age class, sex, and macro-area of residence. RESULTS: The total sample consisted of 1087 PLWH (age 47.9 ± 10.8 years, male 73.5%) and 2218 comparable subjects from the general population. Prevalence of current smokers was 51.6% vs 25.9% (p < 0.001); quitting smoking rate was 27.1% vs. 50.1% (p < 0.001) and the mean number of cigarettes smoked per day was 15.8 vs. 11.9 (p < 0.001), respectively for PLWH and the general population. Smoking and heavy smoking rates amongst PLWH were significantly higher even in subjects who reported diabetes, hypertension and extreme obesity (p < 0.001). Logistic regressions showed that PLWH were more likely current smokers (adjusted Odds Ratio, aOR = 3.11; 95% Confidence Interval (CI) =2.62-3.71; p < 0.001) and heavy smokers (> 20 cigarettes per day) (aOR = 4.84; 95% CI = 3.74-6.27; p < 0.001). PLWH were less likely to have quitted smoking (aOR = 0.36; 95% CI = 0.29-0.46; p < 0.001). CONCLUSION: HIV-infected patients showed a higher rate of current smokers, a larger number of cigarettes smoked and a lower quitting rate than the general population. Our findings emphasize the need for smoking cessation strategies targeting HIV persons.

Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort.

OBJECTIVES: To evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017. PATIENTS AND METHODS: In total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of ≥2.5× upper limit of normal (ULN) for patients with normal baseline values or ≥2.5× baseline for patients with higher baseline values. RESULTS: One hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25-0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02-0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission. CONCLUSIONS: In our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections.

Clusterization of co-morbidities and multi-morbidities among persons living with HIV: a cross-sectional study.

BACKGROUND: Among people living with HIV (PLWH), the prevalence of non-HIV related co-morbidities is increasing. Aim of the present study is to describe co-morbidity and multi-morbidity, their clustering mode and the potential disease-disease interactions in a cohort of Italian HIV patients. METHODS: Cross-sectional analysis conducted by the Coordinamento Italiano per lo Studio di Allergia e Infezioni da HIV (CISAI) on adult subjects attending HIV-outpatient facilities. Non-HIV co-morbidities included: cardiovascular disease, diabetes mellitus, hypertension, oncologic diseases, osteoporosis, probable case of chronic obstructive pulmonary disease (COPD), hepatitis C virus (HCV) infection, psychiatric illness, kidney disease. Multi-morbidity was defined as the presence of two or more co-morbidities. RESULTS: One thousand and eighty-seven patients were enrolled in the study (mean age 47.9 ± 10.8). One hundred-ninety patients (17.5%) had no co-morbidity, whereas 285 (26.2%) had one condition and 612 (56.3%) were multi-morbid. The most recurrent associations were: 1) dyslipidemia + hypertension (237, 21.8%); 2) dyslipidemia + COPD (188, 17.3%); 3) COPD + HCV-Ab+ (141, 12.9%). Multi-morbidity was associated with older age, higher body mass index, current and former smoking, CDC stage C and longer ART duration. CONCLUSIONS: More than 50% of PLHW were multi-morbid and about 30% had three or more concurrent comorbidities. The identification of common patterns of comorbidities address the combined risks of multiple drug and disease-disease interactions.

SLAM Project - Second-Level Diagnostic Assessment: Multidisciplinary approach to HIV Patients.

The aim of the study is to propose a multidimensional second-level diagnostic assessment to allow follow- up in the event physicians observe the presence of risk factors and/or active co-morbidities in HIV-infected patients. To develop our proposal, we chose the Delphi method that has been used for about 30 years in the healthcare field. The CISAI Group (Coordinamento Italiano per lo Studio dell'Allergia in Infezione da HIV) conducted this study. The first phase of the study provided identification of the questionnaire for second-level diagnostic assessment of HIV-infected patients. From March to July 2018 the questionnaire was submitted to 48 experts from 10 Italian HIV-dedicated sites. The questionnaire consisted of 102 items divided into 7 survey areas. The results can be summarized as follows: infectious disease diagnostics, 18 items reached agreement in 9 cases; osteoporosis diagnostics 12 items with 3 agreements; metabolic and cardiovascular diagnostics 13 items with 4 agreements; nephrology diagnostics 19 items with 8 agreements; hepatology diagnostics 12 items with 9 agreements; CNS diagnostics: 18 items with 7 agreements; psychological diagnostics and quality of life assessment (QoL) 10 items with no agreement. If these considerations are confirmed in required discussions and in-depth analyses, they will be able to produce an important indication in the drafting of national guidelines.

Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA).

BACKGROUND: Dyslipidemia represents a significant non-infectious comorbidity among people living with HIV. The aim of this study is to evaluate the impact on lipid profile of switches from an efavirenz (EFV) or protease inhibitor/ritonavir (PI/r)-based regimen to a rilpivirine (RPV) or a once-daily integrase inhibitor-based regimen. METHODS: We analyzed data from SCOLTA prospective database. All patients with HIV-RNA < 50 copies/ml in therapy with two NRTI + EFV or PI/r were included if they switched from EFV to dolutegravir (group EFV-DTG), elvitegravir (EFV-EVG), or RPV (EFV-RPV) and from PI/r to DTG (PI/r-DTG), PI/r to EVG (PI/r-EVG), or PI/r to RPV (PI/r-RPV). Total cholesterol (TC), TC/HDL ratio, LDL-cholesterol (LDL) and triglycerides (TG) were compared at baseline, six months and one year. Comparisons among groups were performed by a general linear model. RESULTS: Four hundred and ninety patients were enrolled, 24.9% female, mean age 47.3 years (±10.1). According to ART switch, 11.4% were classified in group EFV-DTG, 3.9% in EFV-EVG, 23.9% in EFV-RPV, 17.6% in PI/r-DTG, 17.8% in PI/r-EVG, and 25.5% in PI/r-RPV. After adjusted analysis, TC significantly decreased in all groups but EFV-EVG, TC/HDL in all but EFV-DTG and EFV-EVG, while the reduction of TG was significant only in switches to RPV (EFV-RPV and PI/r-RPV). The one year decrease of TC, TC/HDL, LDL and TG was higher in patients with higher baseline levels of the same variable (p < .0001 for all). CONCLUSIONS: In SCOLTA, all switches from PI/r regimens gave advantages on lipid profile, while stopping EFV had consistently favorable lipid effects only if replaced by RPV.

HPV infection and pre-neoplastic cervical lesions among 321 HIV+ women in Florence, Italy, 2006-2016: prevalence and associated factors.

Women living with HIV (WLWH) are at higher risk for HPV-related malignancies. To estimate the factors associated to HPV infection and to pre-neoplastic cervical lesions, we observed 321 WLWH in an HIV care-centre in Florence, Italy. In 2006-2016, WLWH followed at S. Maria Annunziata Hospital underwent to gynaecological examination including HPV-test, Pap-smear, colposcopy and, if needed, cervical biopsy. Demographical and clinical information were collected and linear logistic regression was performed. Among 321 WLWH, 161 (50.2%) resulted HPV+. Multiple genotypes were identified in 35%, and cancer high-risk genotypes in 61%. Younger age, not-caucasic origin, increasing number of partners, and shorter duration of HIV are associated with HPV infection. A colposcopy was performed in 154 HIV+/HPV+ women: histological lesions were present in 47 (30%). Among these, CIN1, CIN2 and CIN3 were present in 16, 4, and 1 patients, respectively. Being caucasic, smoking 1-20 cigarettes/day, having 2 partners in the last year, and being an injective-drug-user are associated with cervical lesions. The use of bi-valent, 4-valent and 9-valent HPV vaccines would potentially prevent lesions in 19%, 33%, and 48%. Among WLWH efficaciously in care for HIV, demographic and behavioral factors mainly contribute to acquisition of HPV and to development of cervical lesions.

Variants in the CYP7B1 gene region do not affect natural resistance to HIV-1 infection.

BACKGROUND: The genetic bases of natural resistance to HIV-1 infection remain largely unknown. Recently, two genome-wide association studies suggested a role for variants within or in the vicinity of the CYP7B1 gene in modulating HIV susceptibility. CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses. We analyzed the frequency of two previously described CYP7B1 variants (rs6996198 and rs10808739) in three independent cohorts of HIV-1 infected subjects and HIV-1 exposed seronegative individuals (HESN). FINDINGS: rs6996198 and rs10808739 were genotyped in three case/control cohorts of sexually-exposed HESN and HIV-1-infected individuals from Italy, Peru and Colombia. Comparison of the allele and genotype frequencies of the two SNPs under different models showed that the only significant difference was seen for rs6996198 in the Peruvian sample (nominal p = 0.048, dominant model). For this variant, a random-effect meta-analysis yielded non-significant results (dominant model, p = 0.78) and revealed substantial heterogeneity among cohorts. No significant effect of the rs10808739 allelic status on HIV-1 infection susceptibility (additive model, p = 0.30) emerged from the meta-analysis. CONCLUSIONS: Although our study had limited power to detect association due to the small sample size, comparisons among the three cohorts revealed very similar allelic and genotypic frequencies in HESN and HIV-1 positive subjects. Overall, these data indicate that the two GWAS-defined variants in the CYP7B1 region do not strongly influence HIV-1 infection susceptibility.

Prevalence of HDV infection in people living with HIV: Data from a multicenter Italian cohort.

Objectives: The development of novel antiviral agents active against Hepatitis Delta Virus (HDV) might change the natural history of chronic infection, reducing the risk for end-stage liver disease. People living with HIV (PWH) are at risk for bloodborne pathogens infection, but limited data on epidemiology of HDV infection is available in this setting. The aim of this study was to investigate HDV prevalence and attitude toward HDV testing and treatment in infectious diseases centers. Methods: A cross sectional survey was performed among centers participating in the CISAI (Coordinamento Italiano per lo Studio dell'Allergia in Infezione da HIV) Group. The survey addressed anti-HDV prevalence and HDV-RNA detectability rates in PWH as well as perceived obstacles to treatment. Results: Overall, responses from ten sites were collected. Among participating centers, 316 PWH with HBV chronic infection are currently followed. Of them, 15.2% had positive anti-HDV antibodies, while 13.9% were not tested yet. Overall, 17% of anti-HDV positive PWH tested at least once for HDV-RNA had active HDV infection, and 71% of them had advanced liver disease. Most infectious diseases centers intend to treat locally HDV infection with upcoming anti-HDV drugs, but some concerns exist regarding treatment schedule. Discussion: HDV testing needs to be implemented in PWH. At present, few patients followed in the CISAI centers seem to be candidate to receive new direct active anti-HDV agents, but repeated HDV-RNA measures could change this proportion.

Incident diabetes in course of antiretroviral therapy.

OBJECTIVE: Recent reports of excessive weight gain in people with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitors (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset. DESIGN: Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort. METHODS: All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM. RESULTS: 4366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4 + 460 [interquartile range (IQR) 256-710] cells/mm 3 cells/mm 3 . During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05-1.50).Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 kg 1.03; 95% CI 1.01-1.04), as well as older age (aHR 1.03 by 1 year; 95% CI 1.01-1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95% CI 1.48-3.49), having untreated high blood pressure (aHR 2.90; 95% CI 1.30-6.45) and baseline blood glucose >100 mg/dl (aHR 5.47; 95% CI 3.82-7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM. CONCLUSIONS: Baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort.

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting.

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load < 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (-0.36, p < 0.0001) than in the RPV cohort (-0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT > 40 IU/L experienced a significant decline (-14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

The measurement of the sink properties of triethanolamine (TEA) as a coating for collecting NO2 by using annular diffusion denuders.

This study evaluates the use oftriethanolamine (TEA) as an alternative to routinely used active carbon employed as a coating for collecting NO2 on a diffusion denuder. The study is based on laboratory experiments made by using annular diffusion denuders coated with TEA. The pre-exponential and exponential factors for the first term of the Gormley-Kennedy equation applied to annular geometry were estimated and compared with the corresponding values for other coatings used in previous studies published in the literature. It was found that TEA does not behave as a perfect sink in comparison with other coatings such as treated active carbon and alkaline guaiacol.

Correlates of Treatment and Disease Burden in People Living with HIV (PLHIV) in Italy.

Treatment burden is a multidimensional concept, including several aspects of life of patients affected by chronic conditions. It has been poorly explored in people living with HIV (PLHIV). An online anonymous survey of PLHIV taking antiretroviral therapy (ART) was conducted, in order to investigate the self-reported correlates of disease burden. HIV Treatment and Diseases Burden (TDB) was investigated with a questionnaire containing 31 items in 7 domains. Respondents were stratified in high burden (H-TDB)/low burden (L-TDB) according to overall HIV TDB mean + 1 standard deviation. Factors associated with H-TDB has been evaluated with a logistic regression model. In total, 531 PLHIV completed the questionnaire. 99 PLHIV had a H-TDB (18.6%). PLHIV with H-TDB were younger (p < 0.001), less frequently on current two drug antiretroviral (ARV) regimens (p = 0.01) and more frequently with plasma HIV-RNA >50 copies/mL (p = 0.04). At multivariable regression analysis, younger age (aOR 1.43, 95%CI 1.14-1.80; p = 0.002), not fully treatment satisfaction (aOR 2.19, 95%CI 1.28-3.74; p = 0.004), the need of a more accurate dialogue with treating physician (aOR 2.29, 95%CI 1.21-4.36, p = 0.01) and a self-declared lower overall Health Status (aOR 1.75, 95%CI 1.33-2.32; p = 0.002) were all associated with a H-TDB. One out of five PLHIV showed a high level of treatment and disease burden. Younger age, not fully satisfaction with ART and need of interaction with a tailored health system should be taken into consideration as correlates of treatment and disease burden in a patient-centered approach, to reduce the negative impact that it can produce on the overall perceived health status of the person.

Reversibility of Central Nervous System Adverse Events in Course of Art.

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naïve to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19−0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts.

Trajectories of CD4+/CD8+ T-Cells Ratio 96 Weeks after Switching to Dolutegravir-Based Two-Drug Regimens: Results from a Multicenter Prospective Cohort Study.

The aim of the present study was to evaluate CD4/CD8 dynamics in patients on dolutegravir (DTG)-based two-drug regimens (2DRs) and compare them with DTG-containing triple-drug regimens (3DRs). A prospective observational study was performed in the context of the SCOLTA cohort. Experienced PWH with HIV-RNA < 50 copies/mL were included if they were on the DTG-2DR, the DTG + tenofovir/emtricitabine (TDF/FTC) regimen, the DTG + tenofovir alafenamide (TAF)/FTC regimen, or the DTG + abacavir/lamivudine (ABC/3TC) regimen; they were followed-up for at least one year. A total of 533 PWH were enrolled, 120 in the DTG + 3TC group, 38 in the DTG + protease inhibitors (PI) group, 67 in the DTG + rilpivirine (RPV) group, 49 in the DTG + TDF/FTC group, 27 in the DTG + TAF/FTC group, and 232 in the DTG + ABC/3TC group. After one year, the CD4/CD8 ratio significantly increased in the PWH treated with DTG + 3TC (+0.08 ± 0.26), DTG + TDF/FTC (+0.1 ± 0.19), and DTG + ABC/3TC (+0.08 ± 0.25). At two years, the CD4/CD8 increase was confirmed for PWH on DTG + TDF/FTC (+0.16 ± 0.28) and DTG + ABC/3TC (+0.1 ± 0.3). In the SCOLTA cohort, PWH on 2DRs experienced a CD4/CD8 increase only in the DTG + 3TC group. Controlled studies with longer follow-up will clarify the long-term immunological and clinical impacts of DTG-2DR.