Molecular Imaging of Vascular Calcification with 18F-Sodium-Fluoride in Patients Infected with Human Immunodeficiency Virus.

18F-Sodium Fluoride (NaF) accumulates in areas of active hydroxyapatite deposition and potentially unstable atherosclerotic plaques. We assessed the presence of atherosclerotic plaques in 50 adult patients with HIV (HIV+) who had undergone two cardiac computed tomography scans to measure coronary artery calcium (CAC) progression. CAC and its progression are predictive of an unfavorable prognosis. Tracer uptake was quantified in six arterial territories: aortic arch, innominate carotid artery, right and left internal carotid arteries, left coronary (anterior descending and circumflex) and right coronary artery. Thirty-one patients showed CAC progression and 19 did not. At least one territory with high NaF uptake was observed in 150 (50%) of 300 arterial territories. High NaF uptake was detected more often in non-calcified than calcified areas (68% vs. 32%), and in patients without than in those with prior CAC progression (68% vs. 32%). There was no correlation between clinical and demographic variables and NaF uptake. In clinically stable HIV+ patients, half of the arterial territories showed a high NaF uptake, often in the absence of macroscopic calcification. NaF uptake at one time point did not correlate with prior progression of CAC. Prospective studies will demonstrate the prognostic significance of high NaF uptake in HIV+ patients.

Prediction of hard cardiovascular events in HIV patients.

OBJECTIVES: To assess the accuracy of risk prediction algorithms used in the general population and an HIV-specific algorithm to predict hard cardiovascular events. METHODS: We compared the pooled equation algorithm (PE) proposed by the American Heart Association with the Framingham risk score (FRS) and the HIV-specific DAD (Data Collection on Adverse Effects of Anti-HIV Drugs) algorithm in a cohort of 2550 HIV+ patients followed for 17 337 patient-years. RESULTS: During follow-up we recorded 67 myocardial infarctions and 2 cardiovascular deaths. PE and FRS identified and missed the same number of events (44 of 69 identified by PE and 49 of 69 by FRS). Similarly, DAD and FRS predicted and missed the same number of events (38 of 64 and 44 of 64 identified, respectively). All algorithms showed moderate sensitivity, specificity and positive predictive values, but high negative predictive values. However, PE and DAD identified more patients with no events than FRS (13.8% and 9.3% net reclassification improvement, respectively). CONCLUSIONS: All algorithms showed a modest predictive ability, although the PE and DAD algorithms identified more patients at low risk.

Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial.

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR). Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders. Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm3; 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12. Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04054089.

Effects of atazanavir, darunavir, and raltegravir on fat and muscle among persons living with HIV.

BACKGROUND: Antiretroviral therapy (ART) is associated with gain in quantity of fat and muscle, but the impact on quality is less understood. The objective of this study was to compare fat and muscle density among people with HIV (PWH) on stable raltegravir (RAL), atazanavir with ritonavir (ATV/r), or darunavir with ritonavir (DRV/r), and explore implications on muscle function. METHODS: Participants from the Modena HIV Metabolic Clinic taking RAL, ATV/r, or DRV/r with at least 1 computed tomography (CT) scan were included. CT scans were reanalyzed for area and density of truncal fat and musculature. Multivariate models explored the effect of ART on fat and muscle density. RESULTS: One hundred six participants were receiving ATV/r, 48 DRV/r, and 141 RAL. In multivariate models (reference ATV/r), only DRV/r was associated with greater subcutaneous (SAT) and visceral adipose tissue (VAT) area, lower lateralis muscle density (more fat), and greater lateralis intermuscular fat area. Compared to ATV/r, RAL was independently associated with less psoas intermuscular fat area. Among all, greater paraspinal muscle density correlated with better physical function. No associations between ART group and physical function were seen among men; DRV/r was associated with stronger grip strength among women. CONCLUSION: DRV/r was associated with greater fat area and lower density of both fat and muscle, and RAL with less intermuscular psoas fat. Higher density psoas and paraspinal musculature were associated with better physical function, suggesting potential clinical relevance of these findings.

18Fluoride-based molecular imaging of coronary atherosclerosis in HIV infected patients.

BACKGROUND AND AIMS: Molecular imaging with 18Fluorodeoxyglucose (FDG) and 18F-sodium-fluoride (NaF) captures arterial inflammation and micro-calcification and can reveal potentially unstable atherosclerotic plaques. METHODS: We performed FDG and NaF PET/CT imaging in two clinically similar cohorts of patients living with HIV (PLWH) with no symptomatic cardiovascular disease. The prevalence and intensity of coronary artery uptake of each tracer, measured as target-to-background ratio (TBR), were assessed in patients at low and high cardiovascular risk. RESULTS: Ninety-three PLWH were submitted to PET/CT imaging with FDG (N = 43) and NaF (N = 50); 42% were at low and 58% at high cardiovascular risk. The intensity of uptake and multivessel coronary artery uptake were significantly higher with NaF than FDG both in low and high-risk patients. When each 18F-tracer was tested in low and high-risk patients, an equal proportion of subjects showed no vessel, single and multivessel NaF uptake; the same was true for no and single vessel uptake of FDG (no multivessel FDG uptake was noted). Waist circumference, CRP, D-dimer, HIV duration and treatment with nucleoside reverse transcriptase inhibitors were associated with high NaF uptake in univariable analyses; D-dimer remained significant in multivariable analyses (OR = 1.05; p=0.02). There were no significant associations with FDG uptake. CONCLUSIONS: The prevalence of coronary artery uptake was higher with NaF compared to FDG both in high and low risk patients, hence microcalcification imaging may be a more sensitive tool to detect coronary atherosclerosis than inflammation imaging. However, the uptake of each 18Fluoride tracer was similar between low and high-risk subjects, and this underscores the discordance between clinical and imaging based risk assessment. Future investigation should address the prognostic significance of NaF coronary artery uptake.

Successful Pre- and Posttransplant Sofosbuvir-Based Anti-Hepatitis C Virus Treatment in Persons Living With Human Immunodeficiency Virus Infection.

This retrospective study reports the data of sofosbuvir-based anti-hepatitis C virus treatment in 24 candidates and 24 recipients of liver transplantation coinfected with human immunodeficiency virus. Sustained virologic response was cumulatively 85% (90% and 100% in those treated with optimal schedules pre- and posttransplant, respectively).

Multidisciplinary approach to the treatment of metabolic and morphologic alterations of HIV-related lipodystrophy.

BACKGROUND: Treatment for metabolic and morphologic alterations in HIV-related lipodystrophy include medical therapy, physical exercise, and surgical interventions. METHOD: We assessed the efficacy and safety of a comprehensive multidisciplinary approach for treating morphological and metabolic alterations of the lipodystrophy syndrome in consecutive patients attending the Metabolic Clinic (MC) of the University of Modena and Reggio Emilia who had at least 2 evaluations over a 48-week period. 245 patients were evaluated: 143 (62.4%) were men, 74 (36.1%) presented with lipoatrophy, 10 (4.9%) with fat accumulation, 93 (45%) with mixed forms, 24 (11.3%) had hypercholesterolemia (LDL >160 mg/dL), 87 (38%) had hypertriglyceridemia (TG >150 mg/dL), 13 (5.7%) had diabetes (glucose >126 mg/dL), and 78 (44%) had insulin resistance (HOMA-IR >4). RESULTS: At follow-up, a significant improvement was observed in both objective and subjective variables. Anthropometric improvement was observed in waist to hip ratio, waist circumference, and right and left cheek dermal thickness measurements. A nonsignificant improvement was observed in fat and lean regional mass by DEXA; CT showed improvement in visceral and subcutaneous adipose tissue. Glucose, HOMA-IR, total cholesterol, and APO B improved. Subjective variables improved in aesthetic satisfaction. CONCLUSION: We conclude that the medical and surgical interventions proposed in this multidisciplinary therapeutic approach are efficacious and safe in the management of lipodystrophy.

Aging with HIV vs. HIV seroconversion at older age: a diverse population with distinct comorbidity profiles.

OBJECTIVE: People aging with HIV might have different health conditions compared with people who seroconverted at older ages. The study objective was to assess the prevalence of, and risk factors for, individual co-morbidities and multimorbidity (MM) between HIV-positive patients with a longer duration of HIV infection, and patients who seroconverted at an older age. We compared estimates across both groups to a matched community-based cohort sampled from the general population. METHODS: We performed a case-control study including antiretroviral therapy (ART)-experienced patients who were HIV seropositive for ≥ 20.6 years ("HIV-Aging"), or who were seropositive for < 11.3 years ("HIV-Aged") having access in 2013 at the Modena HIV Metabolic Clinic. Patients were matched in a 1:3 ratio with controls from the CINECA ARNO database. MM was defined as the concurrent presence of >2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and MM. RESULTS: We analysed 404 HIV-Aging and 404 HIV-Aged participants in comparison to 2424 controls. The mean age was 46.7 ± 6.2 years, 28.9% were women. Prevalence of HIV co-morbidities and MM were significantly higher in the HIV-positive groups compared to the general population (p<0.001) and a trend towards higher rates of MM was found in aging vs aged group. This difference turned to be significant in patients above the age of 45 years old (p<0.001). CONCLUSIONS: People aging with HIV display heterogeneous health conditions. Host factors and duration of HIV infection are associated with increased risk of MM compared to the general population.

Morphologic alterations in HIV-infected people with lipodystrophy are associated with good adherence to HAART.

OBJECTIVE: To evaluate the association between adherence to drugs and morphologic alterations (MOA) in a cohort of HIV-infected patients on HAART. METHOD: This was a cross-sectional multicenter cohort study in eight tertiary Clinical Centers of Northern and Central Italy. Consecutive outpatients taking HAART were enrolled from August 2000 to March 2001. They completed a self-administered questionnaire for the evaluation of signs of MOA and the self-reported adherence to drugs. Main outcome measures were MOA according to the Multicenter AIDS Cohort Study (MACS) definition and adherence to drugs. RESULTS: One hundred seventy-five persons were enrolled into the study. Median CD4 cell count was 522 (interquartile range [IQR] 306-720); 35% of people had undetectable HIV RNA. Patients had been taking HAART for a median of 53 months (IQR 33-62). Among enrolled patients, 83 (47%) had a diagnosis of self-reported MOA; 57 of them reported body changes of more than 12 months duration. Forty persons (23%) self-reported nonadherence in the previous week. Mean time on HAART was 48.7 months (SD = 19.7) for people with MOA and 42.1 months (SD = 21.8) for those without MOA (p =.043). The odds of adherence for people with MOA was 2.36 times (95% CI 1.11-5.00) higher than for people without MOA. On multivariate analysis, being older and female, having an undetectable HIV RNA, longer duration on HAART, and self-reported adherence were independently associated with the presence of MOA. In people with MOA, adherence seems to decrease over time. CONCLUSION: Longer time on HAART and self-reported adherence were correlated to MOA. MOA was also associated with older age and female gender.

Detectable HIV viral load is associated with metabolic syndrome.

BACKGROUND: The aim of our study was to assess the association between HIV viral load (HIV-VL) and metabolic syndrome (MS) in a cohort of HIV-infected patients. METHODS: This is a cross-sectional study including 1324 consecutive HIV-infected patients on stable antiretroviral therapy regimens. RESULTS: Variables significantly associated with MS in univariate analysis were: age [mean +/- SD: 47.04 +/- 7.41 vs 44.07 +/- 6.82, (P < 0.0001)]; male sex [224 (69.35%) vs 614 (61.34%) (P = 0.009)]; Apo B (mg/dL) [111.51 +/- 29.64 vs 100.57 +/- 31.22, (P < 0.0001)]; homeostasis model assessment equation [median (interquartile range), 5.14 (3.00-8.15) vs 2.95 (1.93-4.57), (P < 0.0001)]; body mass index [25.17 +/- 4.40 vs 22.80 +/- 3.38, (P < 0.0001)]; protease inhibitor current use (%) [199 (61.61) vs 529 (52.85), (P = 0.006)]; and log10 HIV-VL [2.17 +/- 0.94 vs 2.02 +/- 0.79, (P = 0.0048)]. MS associated variables in multivariable analysis were: log10 HIV-VL [odds ratio (OR): 1.25; P = 0.003], age (per 10-year increment) [OR: 1.60; P < 0.0001], homeostasis model assessment equation > or =3.8 [OR: 2.77; P < 0.0001]. CONCLUSIONS: Persistent viremia is a significant predictor for the development of MS. Viral control through effective antiretroviral therapy is paramount not only for the control of HIV disease progression but also for the prevention of MS and associated cardiovascular disease.

Severity of lipodystrophy is associated with decreased health-related quality of life.

The impact of lipodystrophy (LD) on quality of life is high, but it has not been demonstrated in literature. The objective of the study was to assess the impact of LD on the health-related quality of life (HRQOL) in HIV-infected people on highly active antiretroviral therapy (HAART). Patients with LD phenotype defined by the Multicenter AIDS Cohort Study (MACS) were included. Three different methods were used to define LD severity: both patient and physician evaluation using the HIV Outpatient Study (HOPS) severity scales and the Lipodystrophy Case Definition (LDCD). The HRQOL was evaluated by MOS-HIV Health Survey. Four hundred one patients on HAART for a mean of 108 +/- 52 months were evaluated for LD at the Metabolic Clinic of Modena and Reggio Emilia University were enrolled from January 2003 to July 2006. According to self-perceived or physician-based HOPS, 106 (26.5%) and 122 (30.4%) patients had severe LD. Females had significantly more severe LD. Few HRQOL scores correlated to LD severity using the physician-based score (both HOPSph and LDCD), while all the HRQOL scores correlated with LD severity when a patient-based score was used (HOPSpt). In multiple linear regression analysis, Mental Health HRQOL score, gender, body mass index, age, body image satisfaction were independent predictors of patient-based (HOPSpt) LD, while none of the HRQOL scores, but female gender, age, waist-to-hip ratio, limb fat, and body image satisfaction were correlated with physician-estimated HOPSph LD severity. HRQOL was strongly correlated with LD severity when a patient-based score was used. For an overall assessment of the impact of LD on HIV-infected people, both patient-based and physician-based measures are required.

Prevalence of and risk factors for pubic lipoma development in HIV-infected persons.

BACKGROUND: The natural history of HIV-associated body habitus changes is unclear. In this report, we describe a novel manifestation of HIV-associated lipoaccumulation. METHODS: We noted the presence of suprapubic fat pads (pubic lipomas [PLs]) in several patients with preexisting HIV-associated body habitus abnormalities. Subsequently, we evaluated the prevalence of and associated risk factors for development of PLs by undertaking an observational cross-sectional study among patients with known lipodystrophy who attended a metabolic clinic in northern Italy. Inclusion criteria were a physician-confirmed diagnosis of lipodystrophy according to the Multicenter AIDS Cohort Study definition and, for those affected with PL, a readily noticeable PL on physical examination. RESULTS: We evaluated 582 patients with lipodystrophy: 214 female (36.7%) and 368 male (63.3%). The overall PL prevalence was 9.4% (95% confidence interval [CI]: 7.2% to 12.1%; P < 0.0001). PLs were more common among obese than nonobese individuals (34.5%, 95% CI: 17.9% to 5l.3% vs. 8%, 95% CI: 5.9% to 10.6%, respectively; P < 0.0001) and those with preexisting dorsocervical fat pads, commonly called "buffalo humps" (BHs) (18.5%, 95% CI: 12.7% to 25.4% vs. 6.1%, 95% CI: 4.03% to 8.83%, respectively, P < 0.0001; relative risk = 3.02, 95% CI: 1.84% to 4.96%, P < 0.0001). The PL prevalence in the nonobese HIV-infected population (body mass index [BMI] <30, n = 550) was 8.0% (95% CI: 5.9% to 10.6%; P < 0.0001). Logistic regression analyses identified the following factors as associated with a greater likelihood for PL: BMI >30 (beta = 0.18, SE = 0.04; P < 0.001), female gender (beta = 1.06, SE = 0.31; P < 0.001), and shorter duration of HIV infection (beta = -0.005, SE = 0.003; P = 0.04). We used a chain graph model to evaluate risk factors for BH and PL simultaneously. A nonnull interaction between these entities was evident, and this association seemed to be independent of factors positively associated with both (BMI and gender). CONCLUSIONS: PL is a newly recognized manifestation of HIV-associated lipoaccumulation that is more likely to occur among those with coexisting dorsocervical fat pads, suggesting the possibility of a common pathogenesis between the 2 entities. Likewise, PLs are more common among women, obese individuals, and those with a shorter duration of HIV infection. We suggest that PL should be considered part of the HIV-associated lipodystrophy syndrome.