Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

The impact of integrase inhibitors on steatosis and fibrosis biomarkers in persons with HIV naïve to antiretroviral therapy.

BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) has a high prevalence among persons with HIV infection. Since Integrase Strand Transfer Inhibitors (INSTIs) are used worldwide and have been associated with weight gain, we must determine their effect in the development of NAFLD and Non-alcoholic Steatohepatitis (NASH) in these patients. The aim of this study was to explore the impact of INSTIs on variation of liver steatosis and fibrosis in the ART-naïve person with HIV, using Hepatic Steatosis Index (HSI), Fibrosis-4 Index (FIB-4), BARD score and NAFLD Fibrosis Score (NFS). METHODS: We performed a monocentric, retrospective cohort study in ART-naïve persons with HIV that initiated INSTI based regimens between December 2019 and January 2022. Data was collected at baseline, 6 and 12 months after initiation. Demographic, clinical and laboratory characteristics, hepatic steatosis, and fibrosis scores were compared between baseline and last visit at 12 months. Linear regression models were performed to analyse the associations between analytical data at baseline and hepatic scores variation during the 12 months of treatment. Models were performed unadjusted and adjusted for age and sex. RESULTS: 99 patients were included in our study. 82% were male and median age was 36 years. We observed a significant increase in body mass index (BMI), HDL, platelet count, albumin, and creatinine and a significant decrease in AST levels. HSI showed no statistically significant differences during follow-up (p = 0.114). We observed a significant decrease in FIB-4 (p = 0.007) and NFS (p = 0.002). BARD score showed a significant increase (p = 0.006). The linear regression model demonstrated a significant negative association between baseline HIV RNA and FIB-4 change (ß= -0.08, 95% CI [-0.16 to -0.00], p = 0.045), suggesting that higher HIV RNA loads at baseline were associated with a greater decrease in FIB-4. CONCLUSION: INSTIs seem to have no impact on hepatic steatosis, even though they were associated with a significant increase in BMI. This might be explained by the direct effect of a dolutegravir-containing regimen and/or by the "return-to-health effect" observed with ART initiation. Furthermore, INSTIs were associated with a reduction in risk of liver fibrosis in ART-naïve persons with HIV, possibly due to their effect on viral suppression.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

The Influence of Antiretroviral Therapy on Hepatitis C Virus Viral Load and Liver Fibrosis in Human Immunodeficiency Virus-Coinfected Patients: An Observational Study.

BACKGROUND: The role of antiretroviral therapy (ART) for Hepatitis C viral load (HCV-VL) and liver fibrosis is poorly understood. This study aimed at evaluating the influence of ART on HCV-VL and liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We conducted a retrospective cohort study of HIV/HCV-coinfected patients followed at a tertiary university hospital. RESULTS: In total, 143 patients were included. In 61 patients, ART initiation was accompanied by an increase in HCV-VL and a decrease in HIV viral load (HIV-VL), whereas ART suspension led to a decrease in HCV-VL and an increase in HIV-VL. Among the 55 HIV-suppressed patients who switched to a raltegravir (RAL)-containing regimen, median HCV-VL levels decreased significantly, while switching to a rilpivirine-containing regimen did not yield a significant reduction. DISCUSSION: If the -treatment of chronic hepatitis starts before ART, ART initiation should be delayed as much as possible. If ART has been started, it is advisable to wait 1 year before initiating chronic hepatitis treatment. RAL as the third agent in an ART regimen could be beneficial in HIV/HCV-coinfected patients, in comparison to other antiretroviral drugs. CONCLUSION: The start and the suspension of ART significantly interferes with HCV-VL in HIV/HCV-coinfected patients.

Routine CD4 monitoring in HIV patients with viral suppression: Is it really necessary? A Portuguese cohort.

PURPOSE: CD4 cell-count has been regarded as the key surrogate marker for prognostic staging and therapeutic monitoring of HIV-infected individuals. Our purpose was to assess the probability of maintaining a CD4 count >200 cells/µL in patients with continuous viral suppression and CD4 cell counts >200 cells/µL. METHODS: Retrospective cohort study of HIV-infected patients, treatment naïve, who started antiretroviral therapy between 2007 and 2011. We estimated the probability of maintaining CD4 counts >200 cells/µL during continuous viral suppression using the Kaplan-Meier method. The hazard ratios of a CD4 count <200 cells/µL were estimated and compared using Cox proportional hazards regression. RESULTS: 401 patients were included: 70.1% men; median age 37 years; 98.8% HIV-1 infected. The median duration of continuous viral suppression with CD4 counts >200 cells/µL was 40.5 months. Ninety-three percent of patients maintained CD4 counts ≥200 cells/µL during the period of continuous viral suppression. Compared with those with an initial CD4 count ≥350 cells/µL, patients with initial CD4 count <300 cells/µL had a significantly higher risk of a CD4 count <200 cells/µL. Patients with viral suppression and CD4 counts ≥350 cells/µL had a 97.1% probability of maintaining CD4 cell counts ≥200 cells/µL for 48 months. CONCLUSIONS: The probability of a CD4 count <200 cells/µL in an HIV-infected patient with viral suppression and CD4 ≥350 cells/µL was very low. These data suggests less frequent monitoring of CD4 counts in these patients.

Prevalence of abacavir-associated hypersensitivity syndrome and HLA-B*5701 allele in a Portuguese HIV-positive population.

BACKGROUND: Human Immunodeficiency Virus (HIV)-positive patients treated with the antiretroviral drug abacavir (ABC) may develop a potentially fatal ABC-associated hypersensitivity syndrome (ABC-HS), typically characterized by fever, malaise, rash, vomiting/diarrhoea and/or dyspnoea/cough. ABC-HS has been strongly associated with HLA-B*57:01 carriage and screening for this allele is recommended. OBJECTIVE: To determine the prevalence of HLA-B*57:01 and to characterize suspected ABC-HS in the adult HIV population from our hospital during a 7-year period. METHODS: Clinical data on patients under ABC treatment from January 2006 to December 2012 were analyzed to search for symptoms of ABC-HS. Reactions of suspected ABC-HS were characterized. HLA-B*57:01 and patch tests (1% and 10% ABC in petrolatum) with readings at 48 h were performed in those without previous testing. From January 2008 routine HLA-B*57:01 screening was implemented. RESULTS: From January 2006 to December 2007, 186 patients began treatment with ABC (data from 163 were available): 7 (4%) patients stopped ABC for suspected ABC-HS (71% males, median age 45 years) and the median time for onset of the reaction after starting ABC was 7 days. Four of the 7 patients had the HLA-B*57:01 allele and 2 of these 4 had positive patch tests. After HLA-B*57:01 screening implementation (January 2008), 573 patients were evaluated and 35 (6.1%) were HLA-B*57:01 positive; no suspected ABC-HS were observed since then. CONCLUSION: Four patients with suspected ABC-HS (of 6 screened) were HLA-B*57:01 positive. No ABC-HS occurred since January 2008, after HLA-B*57:01 screening was implemented.

Prevention of mother-to-child transmission: experience of a Portuguese centre.

INTRODUCTION: HIV infection during pregnancy still raises controversial issues. Combined antiretroviral therapy (cART) has been successful in reducing mother-to-child transmission (MTCT). Routine screening in pregnancy and in pre-conception consultation proved to be one of the best methods able to get this treatment on time. We review our experience with pregnant patients with HIV infection. MATERIALS AND METHODS: Retrospective and descriptive study. Data obtained from HIV-infected pregnant women from 1999 to 2012 with delivery and subsequent infectious diseases follow-up at our hospital. RESULTS: We evaluated 136 patients (169 pregnancies), with a total of 147 living newborns (2 twin pregnancies) and 1 stillbirth. Median age at pregnancy was 30 (SD 5.7) years. Four patients were HIV-2 infected and one HIV-1+2 infected. 26 (19.1%) women were HCV co-infected and 6 (4.4%) HBV co-infected; 1 patient has HCV and HBV co-infection. Sexual risk for HIV acquisition was determined in 102 (75%) patients and 31 (22.8%) were intravenous drug users. 33/136 (24.2%) women were diagnosed on routine screening in pregnancy, 4 during delivery and 2 immediately after delivery. 36 (26.4%) patients had an AIDS-defining entity before pregnancy and no new opportunistic infections were diagnosed. ART was used in 157 (92.9%) pregnancies and 15 (9.5%) of them were treated only with NRTIs. At the time of delivery 86/144 (59.7%) patients had undetectable viral load (VL) (25 patients without VL determined), 91.7% of those on ART. 119 (70.4%) had a TCD4 cell count above 200 cells/mm(3). MTCT occurred in 3/147 cases (2%): in one mother HIV-1 infection was diagnosed three weeks before delivery, other immediately after delivery and the third woman started cART (2NRTI+1PI/r) in the second trimester of pregnancy, always adherent and without secondary effects, VL at delivery was 50 copies/mL and elective C-section was performed. CONCLUSIONS: The fact that 24% of patients were diagnosed during pregnancy shows the importance of routine screening to all pregnant women. MTCT occurred in three children, but only one was administered cART for prevention.