Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

Background In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). Methods To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, <= 3 or > 3 years). Results In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex. Conclusions Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age

Characteristics and patterns of care of endometrial cancer before and during COVID-19 pandemic

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic

Uterine Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) Treated with Conservative Surgery: Systematic Review of Reproductive Outcomes

Background: Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a rare tumor that represent a diagnostic challenge to both clinicians and pathologists. Hysterectomy is considered the definitive treatment in women who don’t desire to conceive anymore; while myomectomy is suggested in young women who desire to preserve their fertility. The aim of this review is to evaluate the reproductive outcomes in patients submitted to fertility sparing treatment and with a diagnosis of STUMP at the definitive pathological evaluation. Methods: We searched among electronic databases from inception of them through January 2022. The research was conducted using meshes created by the combination of relevant heading term, key words, and word variants for: “uterine smooth muscle tumor of uncertain malignant potential”, “fertility”, “pregnancy”. Results: Seven retrospective studies including 80 women desirous of conceiving after a diagnosis of STUMP were included in this systematic review. Among these, 33 (41.25%) women got pregnant at least once and we recorded a total number of pregnancies of thirty-nine. Almost all deliveries were performed by caesarean section. Two (6.1%) relapses were diagnosed. Patients were submitted to hysterectomy and STUMP was confirmed as the final pathological diagnosis. The median follow-up in patients who delivered live babies was 61 months after surgery. At the last follow-up, all patients were alive without evidence of disease. Conclusions: This review shows that pregnacy seems to be possible and safe after the diagnosis of STUMP. These women should undergo rigorous follow-up and consider hysterectomy after completion of their reproductive plan. This review could be a useful tool for the counseling and the management of women with STUMP who desire to keep their fertility

Post Treatment Sexual Function and Quality of Life of Patients Affected by Cervical Cancer: A Systematic Review

Introduction: The aim of this study is to analyze the available scientific evidence regarding the quality of life (QoL) and sexual function (SF) in patients affected by cervical cancer (CC) after surgical and adjuvant treatments. Materials and Methods: Preliminary research was conducted via electronic database (MEDLINE, PubMed and Cochrane Library) with the use of a combination of the following keywords: SF, QoL, and CC. The principal findings considered in the present review were the study design, the number of patients included in each study, the information about the malignancy (histology and stage of disease), the questionnaires administered, and the principal findings concerning SF and QoL. Results: All studies were published between 2003-2022. The studies selected consisted of one randomized control study, seven observational studies (three prospective series), and nine case control studies. The scores used were focused on SF, QOL, fatigue, and psychological aspects. All studies reported a decreased SF and QOL. The most developed questionnaires were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression scale (HADS), and the Female Sexual Distress Scale (FSDS). Discussion: All studies reported a decreased SF and QOL. In addition to the perception of body image, several factors coexist in influencing the outcomes such as the physical, hormonal, psychological. Conclusions: Sexual dysfunction after CC treatment has a multifactorial aetiology which negatively affects the quality of life. For these reasons, it is important to follow and support patients with a multidisciplinary team (doctors, nurses, psychologists, dieticians) before and after therapy. This type of tailored therapeutic approach should become a standard. Women should be informed about possible vaginal changes and menopausal symptoms after surgery and on the positive effects of psychological therapy

Incident diabetes in course of antiretroviral therapy

Objective: Recent reports of excessive weight gain in people living with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitor (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset. Design: Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort. Methods: All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM. Results: 4,366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4 460 (IQR 256-710) cells/mm3cells/mm3. During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05-1.50).Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 Kg 1.03; 95%CI 1.01-1.04), as well as older age (aHR 1.03 by 1 year; 95%CI 1.01-1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95%CI 1.48-3.49), having untreated high blood pressure (aHR 2.90; 95%CI 1.30-6.45) and baseline blood glucose >100 mg/dL (aHR 5.47; 95%CI 3.82-7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM. Conclusions: baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort

Factors Associated With Weight Gain in People Treated With Dolutegravir

Background: An unexpected excess in weight gain has recently been reported in the course of dolutegravir (DTG) treatment. The aim of the present study was to investigate whether weight gain differs among different DTG-containing regimens.Methods: Adult naive and experienced people with HIV (PWH) initiating DTG-based antiretroviral therapy (ART) between July 2014 and December 2019 in the Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) prospective cohort were included. We used an adjusted general linear model to compare weight change among backbone groups and a Cox proportional hazard regression model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for weight increases >10% from baseline.Results: A total of 713 participants, 25.3% women and 91% Caucasian, were included. Of these, 195 (27.4%) started DTG as their first ART regimen, whereas 518 (72.6%) were ART-experienced. DTG was associated with abacavir/lamivudine in 326 participants, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 148, boosted protease inhibitors in 60, rilpivirine in 45, lamivudine in 75, and tenofovir alafenamide (TAF)/FTC in 59. At 6 and 12 months, weight gain was highest among PWH on TDF/FTC+DTG and TAF/FTC+DTG. Baseline CD4 <200 cells/mm3 (HR, 1.84; 95% CI, 1.15 to 2.96), being ART-naive (HR, 2.24; 95% CI, 1.24 to 4.18), and treatment with TDF/FTC+DTG (HR, 1.92; 95% CI, 1.23 to 2.98) or TAF/FTC+DTG (HR, 3.80; 95% CI, 1.75 to 8.23) were associated with weight gain >10% from baseline. Higher weight (HR, 0.97 by 1 kg; 95% CI, 0.96 to 0.99) and female gender (HR, 0.54; 95% CI, 0.33 to 0.88) were protective against weight gain.Conclusions: Naive PWH with lower CD4 counts and those on TAF/FTC or TDF/FTC backbones were at higher risk of weight increase in the course of DTG-based ART

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting

: Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load < 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (-0.36, p < 0.0001) than in the RPV cohort (-0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT > 40 IU/L experienced a significant decline (-14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART