Early Detection of Cancer and Precancerous Lesions in Persons with HIV through a Comprehensive Cancer Screening Protocol.

BACKGROUND: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. METHODS: Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. RESULTS: Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. CONCLUSIONS: The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.

Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort.

OBJECTIVES: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). METHODS: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. RESULTS: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9-10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41-3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26-0.94, p 0.031). CONCLUSIONS: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH.

Kinetics of emergence of liver complications in hepatitis C virus infected patients and advanced fibrosis, with and without HIV-coinfection, after sustained virological response.

OBJECTIVE: There is scarce available evidence on the distribution over time of liver complications emergence in hepatitis C virus (HCV)-infected patients who achieve sustained virological response (SVR) with direct-acting antiviral (DAA)-based therapy. Therefore, we aimed at describing the kinetics of liver-related events appearance in this setting. DESIGN: A multicentric prospective cohort study. METHODS: HCV-monoinfected and HIV/HCV-coinfected patients from GEHEP-011 cohort, whose inclusion criteria were had achieved SVR with DAA-based therapy; liver stiffness prior to starting treatment at least 9.5 kPa; and available liver stiffness measurement at SVR. SVR was considered as the baseline time-point. RESULTS: One thousand and thirty-five patients were included, 664 (64%) coinfected with HIV. Before DAA-based therapy, 63 (6.1%) individuals showed decompensated cirrhosis. After SVR, 51 (4.9%) patients developed liver complications. Median (Q1-Q3) time to the emergence of hepatic events was hepatic encephalopathy 11 (7-24) months, ascites 14 (6-29) months, hepatocellular carcinoma (HCC) 17 (11-42) months and portal hypertension gastrointestinal bleeding (PHGB) 28 (22-38) months (P = 0.152). We define two profiles of liver complications: those emerging earlier (encephalopathy and ascites) and, those occurring continuously during the follow-up (HCC, PHGB) [median (Q1-Q3) time to emergence 12.7 (6.6-28.2) months vs. 25.4 (12.5-41.53) months, respectively (P = 0.026)]. CONCLUSION: The vast majority of HCV-infected patients who develop liver complications after reaching SVR with DAA do it within 3 years after SVR time-point. Specifically, hepatic encephalopathy and ascites do not usually emerge after this period. Conversely, HCC and PHGB may occur in longer term. It is critical to identify patients at risk of developing hepatic events to continue performing surveillance for them.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Low performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Osteonecrosis in patients infected with HIV: clinical epidemiology and natural history in a large case series from Spain.

BACKGROUND: There is a paucity of data on clinical epidemiology of osteonecrosis in HIV-infected patients. We aimed to describe patients' characteristics and natural history of this poorly known condition. METHODS: All cases of symptomatic HIV-related osteonecrosis diagnosed from 1990 through 2003 in 19 Spanish clinics were reviewed. Functional status at the last visit was assessed with the validated Western Ontario and McMaster Universities Index questionnaire. RESULTS: Of 54 patients analyzed, 29 (53.7%) had a single bone necrosis, and 25 (46.3%) had 2 or more sites involved. Progression of symptoms happened more often in patients with hip involvement (17/39 vs 0/8 patients; P = 0.019). Twenty patients (37%) required surgical intervention. Male sex and higher CD4 cell count were associated with surgery on multivariable analysis. Overall, at the end of the follow-up period, half of the patients had moderate to severe disability (Western Ontario and McMaster Universities Index score > or =60). During a follow-up period of 137 person-years, only 2 new episodes of osteonecrosis were observed (rate of recurrences, 1.5/100 person-years; 95% confidence interval, 0.4-5.1). CONCLUSIONS: HIV-related osteonecrosis is associated with significant disability over time. Location of bone necrosis, sex, and CD4 cell count may influence the outcome. The risk for recurrences for patients who have experienced 1 episode is low.