HERMES is a prospective study, including all treatment-naïve patients attending scheduled visits at hospitals in the CISAI group in 2007. The present cross-sectional analysis aims to assess the ...baseline prevalence and characteristics of Metabolic Syndrome (MS) in a population of HIV-positive treatment-naïve patients. MS was diagnosed using the National Cholesterol Education Program (NCEP) definitions. A total of 292 subjects were enrolled, median age was 37 years, 75% of them were males. The prevalence of MS was 12.3%. The most frequent trio of abnormalities that led to the diagnosis of MS was high blood pressure, triglycerides and HDL. Univariate analysis showed that MS was associated with the following variables: age, education, physical activity, advanced HIV disease (CDC stage C or HIV-RNA >100,000 copies + CD4 <100 cells/mm(3)). Higher educational levels remained protectively associated with MS in multivariate analysis. A higher risk of MS was also associated with advanced HIV disease. Actually, treatment-naïve HIV-positive patients in an advanced stage of the disease have a higher prevalence of abnormal levels of triglycerides, HDL cholesterol and blood glucose than those at a less advanced stage. These findings of the HERMES study suggest, therefore, that HIV infection per se is associated to MS.
Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the ...50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was -1.43 log₁₀ c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).
HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. ...However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.
We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.
The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.
GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.
Objectives
To investigate the use of statins and acetylsalicylic acid (ASA) in HIV people in clinical practice.
Design
A multicenter, nationwide, prospective cohort study, including 1182 consecutive ...HIV patients was conducted.
Methods
Statin and ASA prescription was evaluated in primary and secondary cardiovascular disease prevention, according to the European AIDS Clinical Society (EACS) guidelines.
Results
Followed-up patients (998) were mostly males (70.9 %) with a mean age at enrolment of 46.5 years (SD 9.5). The mean time of follow-up was 3.3 years (SD 0.8). At the last follow-up visit, statins would have been recommended for 31.2 % and ASA for 16 % by EACS guidelines. Conversely, only 15.6 and 7.6 % of patients were on statin and ASA treatment, respectively; only 50.3 % of patients treated with statins achieved recommended low-density lipoprotein cholesterol (LDL-c) levels. At the last follow-up visit, agreement between statin therapy and EACS recommendation was 0.58 (95 % CI 0.52–0.63). The corresponding figure for ASA therapy was 0.50 (95 % CI 0.42–0.58), whereas the agreement for ASA therapy in secondary prevention was 0.59 (95 % CI 0.50–0.68).
Conclusions
The prescription of statins and ASA in HIV-infected patients remains largely suboptimal, as only about 50 % of patients requiring statins and ASA are properly treated. Higher attention on this relevant issue and further investigation are warranted in this at risk population.
•Doravirine (DOR) resistance is uncommon among non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients.•Complete DOR resistance in NNRTI-experienced patients is mainly related to ...Y188L mutation.•Previous efavirenz and etravirine use are associated with detection of DOR resistance.•Previous rilpivirine use is associated with a lower probability of DOR resistance.
This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15–2.02) and ETR use (OR = 1.91, 95% CI 1.34–2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22–0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19–2.58) and ETR use (OR = 1.72, 95% CI 1.10–2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05–0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients.
Objectives
The aim was to evaluate the evolution of transmitted HIV‐1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)‐naïve patients from 2006 to 2016.
Methods
HIV‐1 sequences were ...retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list.
Results
We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL interquartile range (IQR) 169–521 cells/μL, and the median viral load was 4.7 log10 HIV‐1 RNA copies/mL (IQR 4.1–5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non‐B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non‐B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B adjusted odds ratio (AOR) for subtype B vs. non‐B 2.91; 95% confidence interval (CI) 1.93–4.39; P < 0.001, lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75–0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40–0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91–0.99; P = 0.02).
Conclusions
The prevalence of HIV‐1 TDR has declined during the last 10 years in Italy.
Background
We assessed the virological response of dual therapy with DRV/r, plus raltegravir, maraviroc or etravirine, in virological failure patients and in virologically suppressed patients ...collected in the Italian Antiretroviral Resistance Database (ARCA).
Material and methods
The primary endpoint was the percentage of patients remaining free of virological failure (confirmed >50 copies/mL or any change in the regimen). Subjects had a resistance test and at least one follow-up visit. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used.
Results
Sixty-seven percent of the 221 patients started DRV/r with RAL, 20.4 % with ETV, and 12.2 % with MAR; 31.2 % virological failures were observed. At survival analysis, the overall proportion of failure was 29.2 % at 1 year and 33.8 % at 2 years. The proportion of failure was lower in patients starting with undetectable vs. detectable viral load (13.3 and 25.2 % vs. 37.4 and 38.8 % at 1 and 2 years, respectively,
p
= 0.001 for both analyses) and in patients treated with DRV 600 BID vs. 800 QD (HR: 0.56, 95 % CI: 0.31–0.99,
p
< 0.05). By regimen, the adjusted proportional model showed no significant difference among the three regimens. A significant lower risk of failure was associated with higher GSS (HIV-DB HR: 0.53, 95 % CI: 0.32–0.88,
p
= 0.014; Rega 0.60, 0.40–0.88,
p
< 0.01; ANRS 0.55, 0.34–0.90,
p
= 0.017), while a higher risk of failure with detectable HIV-RNA (3.02, 1.70–5.72,
p
< 0.001).
Conclusions
Among experienced patients, the best candidates for dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS.
Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the ...lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection.
We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis.
Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval CI, 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (
= .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (
= .016).
Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.
HIV infection has been associated with increased cardiovascular risk. Twenty-four-hour ambulatory blood pressure (BP) is a more accurate and prognostically relevant measure of an individual's BP load ...than office BP, and the ambulatory BP-derived ambulatory arterial stiffness index (AASI) and symmetric AASI (s-AASI) are established cardiovascular risk factors.
In the setting of the HIV and HYpertension (HIV-HY) study, an Italian nationwide survey on high BP in HIV infection, 100 HIV-infected patients with high-normal BP or untreated hypertension (72% men, age 48 ± 10 years, BP 142/91 ± 12/7 mmHg) and 325 HIV-negative individuals with comparable age, sex distribution, and office BP (68% men, age 48 ± 10 years, BP 141/90 ± 11/8 mmHg) underwent 24-h ambulatory BP monitoring.
Despite having similar office BP, HIV-infected individuals had higher 24-h SBP (130.6 ± 14 vs. 126.4 ± 10 mmHg) and pulse pressure (49.1 ± 9 vs. 45.9 ± 7 mmHg, both P < 0.001), and a lower day-night reduction of mean arterial pressure (14.3 ± 9 vs. 16.3 ± 7%, P = 0.025). Both s-AASI and AASI were significantly higher in HIV patients (s-AASI, 0.22 ± 0.18 vs. 0.11 ± 0.15; AASI, 0.46 ± 0.22 vs. 0.29 ± 0.17; both P <0.001). In a multivariate regression, s-AASI was independently predicted by HIV infection (β = 0.252, P <0.001), age, female sex, and 24-h SBP. In HIV patients, s-AASI had an inverse relation with CD4 cell count (Spearman's ρ -0.24, P = 0.027).
Individuals with HIV infection and borderline or definite hypertension have higher symmetric AASI and 24-h systolic and pulse pressures than HIV-uninfected controls matched by office BP. High ambulatory BP may play a role in the HIV-related increase in cardiovascular risk.
Highlights • We investigated muscle symptoms and creatine phosphokinase (CPK) increases in HIV-infected patients receiving raltegravir. • Muscle symptoms (5.2%) and CPK elevations (21.1%) occurred ...frequently in 21 months of follow-up. • Muscle symptoms and CPK increases caused most discontinuations due to adverse events. • Significant predictors of muscle symptoms were central nervous system symptoms and use of atazanavir. • Monitoring of muscle toxicity in patients receiving raltegravir is recommended.
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