Barbara Beghetto

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.

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.

Multidisciplinary Approach to the Treatment of Metabolic and Morphologic Alterations of HIV-Related Lipodystrophy

Abstract 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.

Quality of Life and Body Image in the Assessment of Psychological Impact of Lipodystrophy: Validation of the Italian Version of Assessment of Body Change and Distress Questionnaire

Lipodystrophy (LD) includes morphologic changes that are distressing to patients with HIV. We tested the validity of an Italian version of the Assessment of Body Change and Distress (ABCD) questionnaire and analysed its relationship to physical and mental aspects of Health-Related Quality of Life. Two hundred and fifty-two patients completed the questionnaires. Construct validity of the ABCD was tested against the MOS-HIV Health Survey, body mass-index (BMI) and CD4+ T-lymphocyte counts. Cronbach’s α for the ABCD total score was 0.94. The ABCD showed the hypothesized moderate correlations to MOS-HIV scales and clinical variables. Preliminary evidence supports the reliability and validity of the Italian version of the ABCD in people with HIV and LD. This questionnaire may be useful to identify people experiencing greater impact of LD, or to evaluate the impact of interventions to treat LD such as plastic surgery.

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.

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 ≥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.

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 (β = 0.18, SE = 0.04; P < 0.001), female gender (β = 1.06, SE = 0.31; P < 0.001), and shorter duration of HIV infection (β = −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.

The natural history of HIV-associated lipodystrophy in the changing scenario of HIV infection

In long‐term HIV‐infected patients, peripheral lipoatrophy (LA) and central lipohypertrophy (LH) appear to be related to the same insults (virus and antiretroviral drugs), but are likely to be associated with different fat depot physiologies. The objective of this study was to describe the natural history of lipodystrophy assessed using dual energy X‐ray absorptiometry (DEXA) and computed tomography (CT) in a large HIV out‐patients metabolic clinic.

Randomized Trial to Evaluate Cardiometabolic and Endothelial Function in Patients with Plasma HIV-1 RNA Suppression Switching to Darunavir/Ritonavir with or without Nucleoside Analogues

Abstract Background: We performed a study to evaluate change in cardiometabolic and endothelial function in HIV-infected patients switching to darunavir/ritonavir (DRV/r) monotherapy versus triple therapy. Methods: The MONARCH trial recruited 30 patients who were taking triple combination therapy and with HIV RNA<40 copies/ mL. Patients were randomized to either DRV/r 800/100 mg once daily (OD) monotherapy or DRV/r 800/100 mg OD plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The primary objective was to assess endothelial function change from baseline to 24 and 48 weeks in brachial artery flow-mediated dilation (FMD) test; changes in endothelial precursor cells (EPCs) and circulating endothelial cells (CECs) were secondary objectives. Results: At baseline, the median age of participants was 43 years, 77% were men, and median CD4 cell count was 585 cells/μL. The median FMD (%) decreased in both arms in the study period (P > .05), with no statistically significant difference between arms (10.7% at baseline and 6.7% at week 48 in the DRV/r + 2 NRTIs arm; 11.1% at baseline and 8.8% at week 48 in the DRV/r arm). The changes at week 48 were similar in the 2 arms for EPCs and CECs. Total cholesterol and low-density lipoprotein (LDL) cholesterol showed larger rises to week 48 in the DRV/r arm monotherapy group than in the triple-therapy group (+26 vs +9 mg/dL for total cholesterol and +14 vs +5 mg/dL for LDL cholesterol). Conclusions: In the MONARCH trial, switching from triple combination treatment to DRV/r, with or without nucleoside analogues, did not translate into clinically meaningful reductions in endothelial function as measured by FMD.

Hepatitis C virus antibody-positive patients with HIV infection have a high risk of insulin resistance: a cross-sectional study.

The aim of the study was to characterize and compare insulin resistance (IR) in hepatitis C virus (HCV)‐antibody (Ab)‐positive and HCV‐Ab‐negative patients with HIV infection.