Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

Statins and aspirin in the prevention of cardiovascular disease among HIV-positive patients between controversies and unmet needs: review of the literature and suggestions for a friendly use.

BACKGROUND: As in non-infected subjects, statins and aspirin have a pivotal preventive role in reducing the cardiovascular related morbidity and mortality in HIV infected patients. The persistence of immune activation in these subjects, could contribute to accelerate atherosclerosis, therefore, these treatments that reduce inflammation could provide additional cardiovascular protection. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. Aim of the present position paper is to provide recommendations aimed to overcome the actual differences and limitations among the current ones and to adapt them to the needs of HIV infected patients. RESULTS: We propose to adopt the new ACC/AHA guidelines, simple to use and cost effective, to use the ASCVD score that seems to estimate more accurately the cardiovascular risk among these patients. We suggest to start statin therapy in all patients with a calculated 10-year risk of a cardiovascular event of 10% or greater. Rosuvastatin and atorvastatin should be preferred. LDL-C target may be adopted. Aspirin should be always associated with a statin, in secondary prevention, while in primary prevention it should be reserved only to patients with ≥ 20% 10-year risk particularly adherent to treatments, and with low risk of bleeding. We suggest to start with a dose of 100 mg/day. Finally, management of antiplatelet agents or novel oral anticoagulants may include selecting antiretrovirals with a lower potential for drug interactions or choosing agents least likely to interact with antiretrovirals. CONCLUSIONS: As demonstrated in surveys, HIV physicians are generally highly committed regarding CVD and autonomous in prescribing statins and ASA. Consequently, in the light of the previously discussed discrepancies among the different guidelines and of the incomplete indications regarding HIV-positive persons, the present suggestions could overcome the actual differences and limitations among the current ones.

Hyperhomocysteinaemia in HIV-infected patients: determinants of variability and correlations with predictors of cardiovascular disease.

OBJECTIVE: We evaluated hyperhomocysteinaemia (HHcy) in a cohort of HIV-infected patients in order to assess its relation to cardiovascular risk (CVR) and identify determinants of HHcy variability. METHODS: Cross-sectional observational study. HIV-infected patients on stable highly active antiretroviral therapy (ART) were evaluated for the presence of the metabolic syndrome, lipodystrophy and traditional CVR factors. Plasma homocysteine levels were measured using high-performance liquid chromatography. RESULTS: Five hundred and sixty-seven patients (38% female) with a median age of 44 years were included in the study. Homocysteine (Hcy) was significantly higher in patients with the metabolic syndrome and lipodystrophy. No significant association was found between Hcy levels and the use of ART. However, Hcy was associated with higher blood pressure, waist circumference and waist-to-hip ratio, total lean body mass, visceral adipose tissue (VAT), VAT/total adipose tissue, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, high-density lipoprotein cholesterol, apolipoprotein A1, B, and creatinine. All 10-year CVR assessment scores were significantly associated with Hcy. In a multivariate regression model, systolic blood pressure, vitamin supplementation and HOMA-IR were significantly and independently related to Hcy. CONCLUSIONS: Hcy is elevated in HIV-infected patients and is significantly associated with increased CVR. Measurement of Hcy might be useful in identifying particularly high-risk populations at whom therapeutic interventions could be targeted.

Hypopituitarism and HIV-infection: a new comorbidity in the HAART era?

Several comorbidities are associated with the HIV infection and may involve also the endocrine-metabolic system. Consistently, the recent development of the therapeutic regimen highly active antiretroviral therapy (HAART) ruled out a significant improvement both in the prognosis and life expectancy of HIV-infected patients, but disclosed also new serious drug-related toxicity. Of these, the lipodystrophy syndrome is the most frequent, occurring in up to 83% of HIV-infected patients under HAART. The HIV-related lipodystrophy is associated with alterations in GH dynamics, affecting both basal and stimulated GH secretion. This GHIGF- I secretive pattern resembles that of severe GH deficiency in adulthood due to pituitary diseases, but without leading to IGF-I serum levels below the normal range. The impairment of pituitary GH secretion has been ascribed to the hormonal and metabolic inhibitory effect due to adipose tissue redistribution in HIV-infected males, since in these patients pituitary GH secretion appeared to be inversely related to visceral adipose tissue accumulation and waist to-hip-ratio. However, whether these patients suffer from a true GH deficiency due to an intrinsic pituitary failure or display only a functional reduction of GH secretion due to visceral adiposity remains still a matter of debate, especially in HIV-infected females.

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

OBJECTIVE: 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. METHODS: This was a single-centre cross-sectional study of 1041 HIV-infected patients (373 HCV-Ab-positive; 167 with detectable plasma HCV RNA). Metabolic and anthropometric assessments were performed, including measurement of IR using the homeostasis model for assessment of insulin resistance (HOMA-IR). RESULTS: The prevalence of IR (i.e. a HOMA-IR score >or=3.8) was significantly higher in HCV-Ab-positive than in HCV-Ab-negative patients (47.7 vs. 32.7%; P<0.0001). On multivariable linear regression analysis, the following variables were associated with HOMA-IR score, expressed as an estimate of the percentage variation (Est.): high-density lipoprotein cholesterol (per 0.3 mmol/L increase: Est.-4.1; P=0.01), triglycerides (per 0.1 mmol/L increase: Est. 0.6; P<0.001), alcohol intake (Est. -12.4; P=0.002), sedentary lifestyle (Est. 14.7; P<0.001), CD4 T-cell count in the highest quartile, i.e. >or=690 cells/microL (Est. 20.7; P=0.002), body mass index in the highest quartiles, i.e. >or=22.54 kg/m2 (Est. 30.5-44.7; P<0.001), waist-to-hip ratio in the highest quartile, i.e. >1 (Est. 30.2; P<0.001) and HCV-Ab positivity (Est. 24.4; P<0.001). CONCLUSIONS: Our data confirm that HCV-Ab positivity is an independent risk factor for IR. Management aimed at correcting known risk factors for IR should be implemented.

Long-term psychometric outcomes of facial lipoatrophy therapy: forty-eight-week observational, nonrandomized study.

The aim of this observational, prospective, nonrandomized study was to assess long-term psychometric outcomes of surgical treatment of HIV-related facial lipoatrophy. Two hundred ninety-nine participants (70.8% male) consecutively attending the Metabolic Clinic of Modena and Reggio Emilia University from November 2005 to July 2006, undergoing surgical interventions for HIV-related facial lipoatrophy were enrolled. Fifty-four (18.1%) underwent facial lipofilling, which consists of the harvesting of a small, intact parcel of fatty tissue with processing that removes the nonviable components and of the transport of fatty parcels through a small cannula to implant the graft in a manner that provides nutrition and anchors the fat to the host tissue. After an initial lipofilling, 24 (8%) needed polylactic acid injections to correct cheek asymmetry, 91 (30.4%) received only polylactic acid infiltrations, and 130 (43.5%) polyacrylamide infiltrations only. Subjective outcome measures were face aesthetic satisfaction, body image perception, depression evaluated by a visual analogue scale (VAS), the Assessment of Body Change and Distress questionnaire (ABCD), and by the Beck Depression Inventory questionnaire, respectively. Objective measure was cheek thickness evaluated by a 7.5-MHz frequency ultrasound probe perpendicular to the skin surface at the nasolabial fold, the corner of the mouth, the zygomatic arch, and centrally between these points in the buccal fat pad area. Both subjective and objective variables were evaluated at baseline and 48 weeks after end of surgical treatment. All 299 participants had significant improvement of the aesthetic satisfaction for the face (VAS from 2.9 +/- 2.1 to 6.2 +/- 2.1, p < 0.0001), of body image satisfaction (ABCD question 7 from 3.8 +/- 1 to 3.1 +/- 1 p < 0.0001 and ABCD question 8 from 70.7 +/- 16.7 to 77.2 +/- 17.2 p < 0.0001), of depression score (Beck score from 11.4 +/- 8.3 to 9.4 +/- 7.8 p = 0.001). Participants experienced a significant augmentation of both cheeks' thickness (right cheek from 4.3 +/- 1.9 mm to 9.5 +/- 3 mm p < 0.0001, left cheek from 4.4 +/- 2 mm to 9.6 +/- 3.1 mm, p < 0.0001). Our data suggest that facial surgery is an important option in the treatment of HIV-related lipoatrophy as an integral part of the management of HIV infection, because of the important and lasting psychological benefits.