Screening for Latent Tuberculosis Infection in People Living with HIV: TUBHIVIT Project, a Multicenter Italian Study.

BACKGROUND: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. METHODS: We performed a prospective study in five referral centers for HIV care in Italy. PLHIV who consented Tto participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI who started chemoprophylaxis were followed until the end of therapy. RESULTS: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, and 6 were lost to follow-up before discriminating between latent and active TB. Among the PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study.

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Evaluation of Myo-Intimal Media Thickness and Atheromatous Plaques in People Living with HIV from the Archiprevaleat Cohort vs. HIV-Negative Subjects.

BACKGROUND: Antiretroviral therapy has allowed a clear improvement in prognosis for HIV patients, but metabolic problems, such as dyslipidemia, remain. This can lead to the development of atheromatous plaques. Our study aims to evaluate whether HIV-positive (HIV+) patients show higher myo-intimal media thickness (IMT) and atheromatous plaques compared to HIV-negative (HIV-) patients. METHODS: To evaluate the association between HIV infection in experienced patients and vascular pathology, we performed a cross-sectional study, observing 1006 patients, 380 HIV+ enrolled in the Archiprevaleat cohort, and 626 HIV- as a control group. All patients underwent a Doppler scan of the supra-aortic vessels. We compared the prevalence of IMT > 1.0 mm and plaques in the two groups. RESULTS: Patients in the HIV+ group were younger than those in the HIV- group, with a lower prevalence of hypertension and diabetes and higher dyslipidemia. The prevalence of plaques in strata of age was higher in the HIV+ group than in the HIV- group and was associated with the length of ART exposure. CONCLUSIONS: Our cross-sectional, retrospective study shows that HIV+ experienced patients are at greater risk of IMT and atheromatous plaques compared to HIV-. The risk is associated with being HIV+ and with the length of ART exposure. This finding may be useful in preventing cardiovascular risk.

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.

Role of mode of induction and delivery and women's satisfaction after induction of labour at term: An observational study.

This cross-sectional study aimed at evaluating the impact of different modalities of induction of labour (IOL) and delivery on levels of woman' satisfaction. All women aged 18 years or older, who underwent IOL for at-term pregnancy (≥41 weeks of gestation) in randomly selected days during the study period in 6 participating centres were eligible for the study. The questionnaire investigated women's opinion regarding information about induction, pain control, length of induction, their experience about induction, labour and delivery and their attitude towards induction in a subsequent pregnancy. Women were also asked to fill in the Italian version of the Birth Satisfaction Scale-Revised (BSS-R). A total of 300 women entered the study. The answer to the question about a "positive attitude towards induction in a subsequent pregnancy was "absolutely yes" or "yes" respectively in the 77.8%, 52.8% and 48.6% of women who were induced with oral drugs, vaginal drugs and Cook balloon (heterogeneity chi-square p = 0.05). The corresponding values for women who delivered vaginally or by caesarean section (CS) were 63.3% and 36.4% (chi-square p = 0.0009). The mean BSS-R total score was higher among women who underwent IOL with oral drugs than with vaginal drugs (p < 0.0001) or Cook Balloon (p < 0.0001), and among women who delivered vaginally than in those who delivered by CS (p < 0.0001). Women were asked "What do you think is important for a method of induction?": 47.3% (95% CI 41.7%-53.0%) of women answered that "should make the induction as painless as possible", 47.0% (95% CI 41.4%-52.7%) "should induce labour quickly", 44.3% (95% CI 38.8%-50.0%) "should be safe for baby". This study showed that vaginal delivery was associated with a higher rate of satisfaction among induced women. Considering mode of induction, oral drugs were associated with a higher level of satisfaction. Control of pain and quick induction were the most appreciated characteristics.

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.

Subclinical atherosclerosis as detected by carotid ultrasound and associations with cardiac and HIV-specific risk factors; the Archi-Prevaleat project.

OBJECTIVES: To evaluate the prevalence of carotid intima-media thickness (IMT) and plaques in a cohort of people living with HIV (PLWH), the role of cardiovascular risk factors, the impact of the antiretroviral regimens and the difference between naïve and experienced patients in the onset of carotid lesions. METHODS: This project was initiated in 2019 and involves eight Italian centres. Carotid changes were detected using a power colour-Doppler ultrasonography with 7.5 MHz probes. The following parameters were evaluated: IMT of both the right and left common and internal carotids, data regarding risk factors for cardiovascular disease, HIV viral load, CD4 cell counts, serum lipids, glycaemia and body mass index. The associations between pathological findings and potential risk factors were evaluated by logistical regression, with odds ratios (ORs) and 95% confidence intervals (95% CI)s. RESULTS: Among 1147 evaluated PLWH, with a mean age of 52 years, 347 (30.2%) had pathological findings (15.8% plaques and 14.5% IMT). Besides the usual risk factors, such as older age, male sex and dyslipidaemia, CD4 cell nadir < 200 cells/mL (adjusted OR = 1.51, 95% CI: 1.14-1.99) and current use of raltegravir (adjusted OR = 1.54, 95% CI: 1.01-2.36) were associated with higher prevalence of pathological findings. CONCLUSIONS: Our data show that the current overall percentage of carotid impairments remains high. Colour-Doppler ultrasonography could play a pivotal role in identifying and quantifying atherosclerotic lesions among PLWH, even at a very premature stage, and should be included in the algorithms of comorbidity management of these patients.

Durability of Dolutegravir-Based Regimens: A 5-Year Prospective Observational Study.

This study evaluates the frequency and causes of dolutegravir (DTG) discontinuation along 5 years of follow-up, in both antiretroviral treatment (ART)-naive and experienced people living with HIV (PLWH). This is a prospective multi-center cohort study enrolling PLWH on DTG from July 2014 until November 2020. DTG-durability was investigated using the Kaplan-Meier survival curve. The Cox proportional-hazards model was used for estimating the hazard ratio (HR) of DTG discontinuation for any cause, and for adverse events (AEs). Nine hundred sixty-three PLWH were included, 25.3% were women and 28.0% were ART-naive. Discontinuations for any causes were 10.1 [95% confidence interval (95% CI) 8.9-11.5] per 100 person-years, similar in most regimens, with the apparent exception of tenofovir alafenamide/emtricitabine+DTG (p < 0.0001). In the multivariable Cox regression model, non-Caucasian ethnicity, age ≥50 years, and lower estimated glomerular filtration rate (eGFR) were associated with a higher probability of DTG interruption. The incidence rate of virological failure was 0.4 (95% CI 0.2-0.7) per 100 person-years, while the estimated discontinuation rate for AEs was 4.0 (3.2-4.9) per 100 person-years. Thirty-four DTG interruptions were due to grade ≥3 events (10 central nervous system, 6 hypersensitivity, 3 renal, 3 myalgia/asthenia, 3 abdominal pain, 2 gastrointestinal, and 7 other events). People with lower body mass index, age ≥50 years, and lower eGFR were at higher risk of AEs, while dual combinations were protective (HR 0.41 compared with abacavir/lamivudine/DTG, 95% CI 0.22-0.77). In this prospective observational study, we found high DTG durability and a low rate of virological failures. Dual therapies seemed protective toward AEs and might be considered, when feasible, a suitable option to minimize drug interactions and improve tolerability.

Impact of prolonged maraviroc treatment on non-AIDS-related comorbidities in HIV-positive patients: a retrospective cohort study.

OBJECTIVES: This retrospective study evaluates the effect of maraviroc, the first CCR5 receptor antagonist, on non-AIDS-related comorbidity incidence and its impact on inflammatory and lipid parameters. METHODS: Seventy-four HIV patients on maraviroc treatment were compared with 312 patients never exposed to maraviroc (matched for sex, age and CD4 nadir). RESULTS: At baseline (T0), maraviroc patients presented a longer duration of HIV infection, a higher prevalence of comorbidities and a greater frequency of polypharmacy. Non-AIDS-defining disease incidence was lower in the maraviroc group than in the non-maraviroc group (without achieving statistical significance). Except triglycerides (TGL), which dropped only in the maraviroc group, inflammatory and immunological parameters did not significantly change in either group by the end of the study period (T3). At T3, high-sensitivity C-reactive protein (hsCRP) and high-density lipoprotein were inversely correlated in both groups (Spearman's rho: maraviroc -0.30, P = 0.05; non-maraviroc -0.23, P = 0.0003). Only in the non-maraviroc group was the positive correlation between hsCRP and lipids observed both at T0 (hsCRP/low-density lipoprotein (LDL) +0.17, P = 0.004; hsCRP/total cholesterol +0.20, P = 0.0007; hsCRP/TGL +0.12, P = 0.04) and T3 (hsCRP/LDL +0.26, P < 0.0001; hsCRP/total cholesterol +0.24, P = 0.0001; hsCRP/TGL +0.15, P = 0.02). These correlations were not found in the maraviroc group. A significant positive correlation was found at T0 and at T3 between hsCRP and D-dimer in both groups (maraviroc: T0 +0.46, P = 0.0007; T3 +0.41, P = 0.006; non-maraviroc: T0 +0.17, P = 0.02; T3: +0.17, P = 0.017). CONCLUSIONS: These data suggest a possible protective role of maraviroc in the incidence of non-AIDS-related comorbidities in a population with longer-lasting infection and allow us to hypothesize its role in the modulation of lipid-dependent inflammation.

Cardiovascular risk in advanced naïve HIV-infected patients starting antiretroviral therapy: Comparison of three different regimens - PREVALEAT II cohort.

BACKGROUND AND AIMS: PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naïve patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk. METHODS: The study included all consecutive naïve patients with less than 200 CD4 cells/ml starting antiretroviral therapy. Our primary objective was to evaluate changes in carotid intima- media thickness (IMT). Secondary endpoints included changes in flow mediated vasodilation (FMD), inflammatory markers, triglycerides and cholesterol. Patients were evaluated at time 0, and after 3, 6 and 12 months. RESULTS: We enrolled 119 patients, stratified into three different groups: patients receiving atazanavir/ritonavir boosted (ATV/r) based regimens, efavirenz (EFV) based regimens and darunavir/ritonavir boosted (DRV/r) based regimens. At baseline, advanced naïve patients showed a relevant deterioration of CV conditions in terms of traditional CV risk factors, endothelial dysfunction and serum biomarkers. During the 12-month follow up period, mean blood lipids significantly increased: total cholesterol from 159 to 190 mg/dL, HDL-C from 31 to 41 mg/dL, and LDL-C from 99 to 117 mg/dL. D-dimers steadily decreased (median level 624 at baseline and 214 at T3), whereas ICAM and VCAM consistently raised. DRV/r and ATV/r determined a more marked decrease of D-dimers as compared to EFV. Regarding the epi-aortic changes (IMT >1 mm or presence of atherosclerotic plaques), patients in the DRV/r group were at risk of developing pathological IMT during the study (OR 6.0, 95% CI 0.9-36.9), as compared to EFV ones. CONCLUSIONS: CV risk was elevated in advanced naïve patients and tended to remain high in the first year of therapy.

Atherosclerosis is associated with multiple pathogenic mechanisms in HIV-infected antiretroviral-naive or treated individuals.

OBJECTIVES: HIV-infected patients have a greater burden of sub-clinical and clinical atherosclerotic disease compared to the general population. The primary objective of this study was to compare the relative roles of inflammation, endothelial alterations, and metabolic factors in the induction and maintenance of atherosclerosis in antiretroviral therapy (ART)-treated or ART-naive patients. DESIGN: Cross-sectional study; 79 HIV-infected patients (55 ART-treated and 24 naive individuals) were consecutively enrolled. In both groups, nearly 50% of the individuals had a high cardiovascular risk (Framingham value >20%). METHODS: Echo-Doppler [intima-media thickness (IMT)], inflammatory, thrombophilic, endothelial, metabolic indexes, and cholesterol efflux molecules were evaluated. Multivariate analysis adjusted for age, CD4 nadir, BMI, and Framingham's score were used to analyze the results. RESULTS: A complex pathogenesis drives atherogenesis in HIV infection. Thus, whereas inflammation could be responsible for this process in ART-naive individuals, metabolic factors [low-density lipoprotein (LDL), apolipoprotein B (ApoB), lipoprotein A] seem to play a more prevalent role in ART-treated patients. Notably, ABCA-1, an ATP-binding transporter cassette protein involved in cholesterol efflux, which is inhibited by Nef, is up-regulated in ART-treated individuals. CONCLUSION: Atherosclerosis in HIV infection results from the interaction of multiple factors: an inflammatory and HIV-driven disease could prevail in the absence of therapy; metabolic, non-inflammatory causes may be more important in patients undergoing therapy. Approaches to atherosclerotic disease in HIV infection should consider these differences.