Observational cohort study of rilpivirine (RPV) utilization in Europe

INTRODUCTION Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. METHODS Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann-Whitney U test and Chi-square test. A logistic regression model was used to compare participants' characteristics by treatment group. Kaplan-Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). RESULTS 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3-5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001). CONCLUSION Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS)

A bioinformatic approach to identify new potential resistance relevant amino acid substitutions (AAS) in HIV-1 protease (H1P)

Background: Predicting potential drug resistance mutations are important when evaluating protein-drug interactions of potential new antiviral drugs. Here we used evolutionary data from the Retroviral Aspartyl Protease (RVP) family (PF00077, 54135 sequences) to estimate plausible PI resistant-associated AAS within the H1P. Methods: Using a Hidden Markov Model (HMM) of the RVP family probabilities were extracted for each possible AAS limited to the 38 positions reported in the IAS drug resistance listing for H1P (December 2008 version). The HMM is a dynamic Bayesian network, modeling sequences of amino acids. The HMM is based on curated and representative sequences from the RVP family. Results: Theoretically 760 AAS (20 × 38) are possible for the 38 evaluated positions within the H1P. Of these, the RVP-HMM detected a total of 229 AAS (30.1%) with a probability above 1/20 (0.05). Of the 229 AAS, 51 (70%) were among the 73 AAS included in the IAS listing as PI-resistant mutations, leaving 178 AAS with P > 0.05 as evolutionary plausible. Conclusion: Based on exploration of the RVP family by HMM, 70% of the established PI-resistant associated AAS could be predicted to occur. Additional 178 AAS was identified as evolutionary plausible and potentially could allow for drug-resistance. In conclusion, we provide a probability landscape of plausible/unfavorable AAS based on inherited structure through evolution and genetic distance, which could prove useful for future drug design

Predictive Factors for Pregnancy-Related Persistent Pelvic Girdle Pain (PPGP): A Systematic Review

Background and Objectives: To identify the most frequently reported predictive factors for the persistency of pregnancy-related pelvic girdle pain (PPGP) at 3–6 months after childbirth in women with PPGP alone or PPGP in association with pregnancy-related lower back pain (PLBP). // Methods: Eligibility criteria: Two authors independently selected studies excluding PPGP determined by a specific, traumatic, gynecological/urological cause or isolated PLBP and studies that did not include the presence/absence of PPGP as the the primary outcome. We, instead, included studies with an initial assessment in pregnancy (within 1 month of delivery) and with a follow-up of at least 3 months after delivery. // Data sources: The research was performed using the databases of Medline, Cochrane, Pedro, Scopus, Web of Science and Cinahl from December 2018 to January 2022, following the indications of the PRISMA statement 2021 and the MOOSE checklist. It includes observational cohort studies in which data were often collected through prospective questionnaires (all in English). // Study appraisal and risk of bias: Two independent authors performed evaluations of the risk of bias (ROB) using the quality in prognostic studies (QUIPS) tool. // Synthesis of results: An in-depth qualitative analysis was conducted because, due to a high degree of heterogeneity in the data collection of the included studies and a lack of raw data suitable for quantitative analysis, it was not possible to carry out the originally planned meta-analyses for the subgroups. // Results: The research process led to the inclusion of 10 articles which were evaluated using the QUIPS tool: 5 studies were evaluated as low ROB and 5 were evaluated as moderate ROB. High levels of pain in pregnancy, a large number of positive provocation tests, a history of lower back pain and lumbo-pelvic pain, high levels of disability in pregnancy, neurotic behavior and high levels of fear-avoidance belief were identified as strong predictors of long-term PPGP, while there was weak or contradictory evidence regarding predictions of emotional distress, catastrophizing and sleep disturbances. // Discussion: The impossibility of carrying out the meta-analysis by subgroups suggests the need for further research with greater methodological rigor in the acquisition of measures based on an already existing PPGP core predictors/outcome sets

Minor mutations in HIV protease at baseline and appearance of primary mutation 90M in patients for whom their first protease-inhibitor ntiretroviral regimens failed

The association between minor mutations in human immunodeficiency virus (HIV) protease at baseline and development of common primary mutation 90M at virological failure (conferring some resistance to all protease inhibitors [PIs]) was evaluated in 93 previously drug-naive patients experiencing failure of their first PI-based antiretroviral regimens. In logistic regression analysis, the probability of accumulating a new 90M mutation at virological failure was associated with the presence at baseline of minor mutation 36I (naturally occurring in ∼25% of HIV clade B and in &gt;80% of HIV non-clade-B viruses) (adjusted odds ratio, 13.5 [95% confidence interval, 1.89–95.6]; P=.009) and, possibly, of 10I/V. This suggests a potential role for the presence of 36I at baseline in predicting the appearance of 90M at virological failure

Evaluation of the prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy

Whilst renal dysfunction, especially mild impairment (60&#60;eGFR&#60;90 ml/min), has been often described in HIV-infected population, its potential contribution to HIV evolution and risk of cerebro-cardiovascular disease (CCVD) has not been clarified. Data from HIV-1 infected patients enrolled in the Italian Cohort of Antiretroviral-Naïve (Icona) Foundation Study collected between January 2000 and February 2014 with at least two creatinine values available. eGFR (CKD-epi) and renal dysfunction defined using a priori cut-offs of 60 (severely impaired) and 90 ml/min/1.73m2 (mildly impaired). Characteristics of patients were described after stratification in these groups and compared using chi-square test (categorical variables) or Kruskal Wallis test comparing median values. Follow-up accrued from baseline up to the date of the CCVD or AIDS related events or death or last available visit. Kaplan Meier curves were used to estimate the cumulative probability of occurrence of the events over time. Adjusted analysis was performed using a proportional hazards Cox regression model. We included 7,385 patients, observed for a median follow-up of 43 months (inter-quartile range [IQR]: 21-93 months). Over this time, 130 cerebro-cardiovascular events (including 11 deaths due to CCVD) and 311 AIDS-related events (including 45 deaths) were observed. The rate of CCVD events among patients with eGFR &#62;90, 60-89, &#60;60 ml/min, was 2.91 (95% CI 2.30-3.67), 4.63 (95% CI 3.51-6.11) and 11.9 (95% CI 6.19-22.85) per 1,000 PYFU respectively, with an unadjusted hazard ratio (HR) of 4.14 (95%CI 2.07-8.29) for patients with eGFR &#60;60 ml/min and 1.58 (95%CI 1.10-2.27) for eGFR 60-89 compared to those with eGFR &#8805;90. Of note, these estimates are adjusted for traditional cardio-vascular risk factors (e.g. smoking, diabetes, hypertension, dyslipidemia). Incidence of AIDS-related events was 9.51 (95%CI 8.35-10.83), 6.04 (95%CI 4.74-7.71) and 25.0 (95%CI 15.96-39.22) per 1,000 PYFU, among patients with eGFR &#62;90, 60-89, &#60;60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR &#60;60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90&#60;eGFR&#60;60) seem to be at increased risk of cerebro-cardiovascular morbidity and mortality

The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: a nested case–control study

Background: Elevated high-sensitivity C-reactive protein (hsCRP) increases the risk of cardiovascular disease (CVD) in the general population, but its role as a predictive marker in HIV-positive patients remains unclear. Aim of the study was to evaluate whether hsCRP or other biomarkers are independent predictors of CVD risk in HIV-infected patients.Methods: Retrospective, nested case-control study. HIV-positive men and women (35-69 years of age) receiving combination antiretroviral therapy (cART) were included. Cases (n = 35) had a major CVD event. Controls (n = 74) free from CVD events for at least 5 years from starting ART were matched on diabetes and smoking. HsCRP, D-dimer, P-selectin, interleukin-6 (IL-6), tissue plasminogen activator, plasminogen activator inhibitor-1 levels were measured.Results: High hsCRP was associated with CVD risk, independently of traditional cardiovascular risk factors, HIV replication and the type of ART received at the time of sampling (adjusted odds ratio 8.00 [1.23-51.94] comparing >3.3 mg/L with <0.9 mg/L; P = 0.03). Higher IL-6 and P-selectin levels were also independently associated with increased CVD risk, although the association was weaker than for hsCRP. Higher total cholesterol and lower HDL cholesterol increased CVD risk, independent of hsCRP.Conclusion: hsCRP may be a useful additional biomarker to predict CVD risk in HIV-infected patients receiving cART

Prevalence of Chagas disease and strongyloidiasis among HIV-infected Latin American immigrants in Italy – The CHILI study

INTRODUCTION: Screening HIV-positive migrants for neglected tropical diseases having potential for life-threatening reactivation, such as Chagas disease and strongyloidiasis is not widely implemented. We evaluated the prevalence of these infections among a large cohort of HIV-infected migrants from Latin America living in Italy. METHOD: Cross-sectional study evaluating the prevalence of Trypanosoma cruzi and Strongyloides stercoralis infections in HIV-infected migrants from Latin America enrolled in the Italian Cohort of Antiretroviral-Naïve patients (ICONA) between 1997 and 2018, based on serology performed on sera stored in the ICONA Foundation biobank. Screening for Chagas disease was performed using two commercial ELISA complemented by commercial Immunoblot and CLIA if discordant. Strongyloidiasis was evaluated using a commercial ELISA. RESULTS: 389 patients were analysed. Fifteen (3.86%) had at least one positive Chagas ELISA test. Prevalence of Chagas disease was 0.5% or 1.29% depending on the confirmatory technique. Serology for strongyloidiasis was positive in 16 (4.11%) patients. Only Nadir CD4+ T cell count was associated with discordant serology for Chagas disease (p = 0.046). CONCLUSIONS: The accuracy of seroassays for Chagas disease and strongyloidiasis in HIV-positive patients is unclear. To avoid missing potentially life-threatening infections, we suggest implementing additional diagnostic strategies in at-risk patients with inconclusive serology results