Low risk of bacterial co-infection, opportunistic diseases, and persistent immunosuppression in people living with HIV and COVID-19.

PURPOSE: SARS-CoV-2 infection produces lymphopenia and CD4+ T-cell decrease, which could lead to a higher risk of bacterial co-infection or impair immunological evolution in people living with HIV (PLWH). METHODS: We investigated the rate of co-infection and superinfection, and the evolution of CD4+ count and CD4+/CD8+ ratio, in hospitalized PLWH with COVID-19. RESULTS: From March to December 2020, 176 PLWH had symptomatic COVID-19 and 62 required hospitalization (median age, 56 years, 89% males). At admission, 7% and 13% of patients had leukocytosis or increased procalcitonin values and 37 (60%) received empiric antibiotic therapy, but no bacterial co-infection was diagnosed. There were seven cases of superinfection (12%), and one case of P. jiroveci pneumonia during ICU stay. No significant change in CD4+ count or CD4+/CD8+ ratio was observed after discharge. CONCLUSION: Bacterial co-infection is not frequent in PLWH with COVID-19. Immune recovery is observed in most of patients after the disease.

Factors associated with the number of drugs in darunavir/cobicistat regimens.

BACKGROUND: Darunavir/cobicistat can be used as mono, dual, triple or more than triple therapy. OBJECTIVES: To assess factors associated with the number of drugs in darunavir/cobicistat regimens. METHODS: A nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat in Spain from July 2015 to May 2017. Baseline characteristics, efficacy and safety at 48 weeks were compared according to the number of drugs used. RESULTS: There were 761 patients (75% men, 98% were antiretroviral-experienced, 32% had prior AIDS, 84% had HIV RNA <50 copies/mL and 88% had ≥200 CD4 cells/mm3) who initiated darunavir/cobicistat as mono (n=308, 40%), dual (n=173, 23%), triple (n=253, 33%) or four-drug (n=27, 4%) therapy. Relative to monotherapy, triple therapy was more common in men aged <50 years, with prior AIDS and darunavir plus ritonavir use, and with CD4 cells <200/mm3 and with detectable viral load at initiation of darunavir/cobicistat; dual therapy was more common with previous intravenous drug use, detectable viral load at initiation of darunavir/cobicistat and no prior darunavir plus ritonavir; and four-drug therapy was more common with prior AIDS and detectable viral load at initiation of darunavir/cobicistat. Monotherapy and dual therapy showed a trend to better virological responses than triple therapy. CD4 responses and adverse effects did not differ among regimens. DISCUSSION: Darunavir/cobicistat use in Spain has been tailored according to clinical characteristics of HIV-infected patients. Monotherapy and dual therapy have been common and preferentially addressed to older patients with a better HIV status, suggesting that health issues other than HIV infection may have been strong determinants of its prescription.

Frailty and physical function in older HIV-infected adults.

Background and Objectives: HIV patients have seen accelerated ageing. Our objective was to determine the prevalence of frailty, to evaluate factors associated with frailty and to evaluate physical function in older HIV-infected adults. Design: this was a cross-sectional study. Setting: outpatient clinics of two public university hospitals in Madrid (Spain). Methods: frailty was defined according to the criteria of Fried: shrinking, weakness, poor endurance and energy, slowness and low physical activity level, being frail those who met at least three criteria, prefrail one or two criteria and robust when they met no criteria. Physical function was assessed using standardised methods. Results: we evaluated 117 HIV-infected patients. Mean age was 61.3 ([standard deviation] 6.87) years. All patients were on antiretroviral therapy. Median current CD4+ T-cell count was 638 (144-1871) cells/µl, and median CD4/CD8 ratio was 0.79 (0.00-3.62). The prevalence of frailty was 15.4%, and that of prefrailty was 52.1%. In the multivariate analyses depressive symptoms (OR [95% CI], 9.20 [2.17-39.05]) and CD4/CD8 ratio (OR 0.11 [0.02-0.61]) were associated with frailty. Even though 100% of the patients were able to walk and perform basic activities of daily life independently, functional impairment was high (20% slow gait and 55% Short Physical Performance Battery ≤9). Conclusions: HIV-infected patients aged ≥55 years have a high prevalence of frailty and a high burden of functional impairment. Optimal management of this population requires close collaboration between infectious diseases specialists and geriatricians.

Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response.

BACKGROUND AND AIMS: Fibrosis regression (FR) after sustained virological response (SVR) should produce a better outcome in hepatitis C (HCV)-/HIV-coinfected patients with liver cirrhosis, but there are no specific data in this issue. METHODS: We compared the incidence rate (IR) and the time to develop a liver complication and death in 133 cirrhotic patients according to SVR or/and FR. RESULTS: Of 42 patients with SVR, 23 (55%) had FR, in comparison with only 14 of the 91 (15%) without SVR. During a follow-up of 6.8 years (916.8 person-years), the IR of death, liver-related death, and liver-related complications were 2.45, 0.61, and 1.22 per 100 persons/year among SVR/FR, and 7.6, 5.9, and 6.81 among non-SVR without FR (p < 0.01), respectively. SVR patients without FR had also a lower rate of liver-related complications (1.78 vs 3.25; p = 0.02), but a worse IR of death (5.36) and liver-related death (2.68) than non-SVR patients with FR (1.3, and 0.65; p < 0.01). Moreover, FR was associated with less hospital admissions and decreasing alpha-fetoprotein levels. In Cox analysis, only FR was associated with a lower risk of death (adjusted hazard ratio, HR 0.36; 95% CI 0.15-0.86), and liver-related death (HR 0.15; 95% CI 0.03-0.65), whereas both FR (HR 0.09; 95% CI 0.03-0.3, p < 0.01) and SVR (HR 0.24; 95% CI 0.07-0.87) decreased the risk of liver-related complications. CONCLUSION: Fibrosis regression after SVR is associated with the highest reduction in death of any cause, liver-related mortality, and liver-related complications in HIV-/HCV-coinfected patients with cirrhosis.

Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C).

OBJECTIVES: To describe raltegravir pharmacokinetics at steady-state in HIV/hepatitis C virus (HCV)-coinfected patients under antiretroviral (ARV) treatment with (n = 5) and without (n = 5) advanced liver cirrhosis (Child-Pugh C). METHODS: This was a non-randomized, Phase I, parallel-assignment, open-label pharmacokinetic study in HIV/HCV-coinfected patients with Child-Pugh grade C hepatic cirrhosis. We recruited clinically stable HIV/HCV-coinfected adult patients with controlled HIV viraemia (<50 copies/mL) for at least 6 months. Raltegravir (400 mg twice daily) was added under fasting conditions for 5 days to the successful ritonavir-boosted protease inhibitor-based ARV regimen. The trial was registered in the ClinicalTrials.gov database (NCT01289951) (LIVERAL). RESULTS: Raltegravir AUC0-12 and C12 were increased 1.72-fold (90% CI, 1.02 to 2.92) and 6.58-fold (90% CI, 2.92 to14.85), respectively, in patients with advanced liver cirrhosis. No safety issues were identified and raltegravir was well tolerated by all patients. CONCLUSIONS: Raltegravir plasma levels are increased in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). Despite the higher exposure, raltegravir was safe and well tolerated.

Virological response to short-course maraviroc monotherapy does not predict viral tropism in HIV-1-infected treatment-naive patients.

OBJECTIVES: We aimed to evaluate whether virological response to a short course of maraviroc monotherapy could predict HIV-1 tropism. METHODS: A clinical trial was performed in HIV-1 treatment-naive patients infected with R5- or non-R5-tropic virus determined using the Trofile(®) assay, with >1000 HIV-1 RNA copies/mL. Maraviroc was administered for 10 days. Viral load was measured at baseline and days 4, 7, 10 and 28. The main outcome measurement was the decline in HIV-1 RNA at day 10. The trial was registered in the ClinicalTrials.gov database (NCT01060618; TROPISMVC). RESULTS: Forty patients [30 R5 and 10 dual/mixed (D/M)] were recruited. There was a significant decrease in HIV-1 RNA after 10 days of maraviroc treatment in patients with R5-tropic virus (median 1.52 log10 RNA copies/mL; 95% CI 1.23-1.63; P < 0.0001), but also in patients with D/M-tropic virus (median 1.62 log(10) RNA copies/mL; 95% CI 0.33-1.88; P = 0.00024). The difference in the HIV-1 RNA decrease (-0.16 log(10) RNA copies/mL; 95% CI -0.53 to 0.22) was not significant (P = 0.410). A decrease >0.5 log(10) RNA copies/mL was found in 96.3% of patients with R5-tropic virus and in 70% of patients with D/M-tropic virus (P = 0.052). The differences were not significant when a decline of 1 log(10) RNA copies/mL was considered (92.6% versus 70%; P = 0.11). CONCLUSIONS: Treatment-naive patients infected with R5- or D/M-tropic virus have similar virological responses to a short course of maraviroc monotherapy. This clinical test thus cannot be used as a surrogate marker of viral tropism in this population.

Central nervous system antiretroviral penetration and cognitive functioning in largely pretreated HIV-infected patients.

Prolonged time on effective antiretroviral therapy (ART) should be associated with a low incidence of neurocognitive impairment (NCI). We investigated the rate of NCI in 162 largely pretreated patients with HIV RNA suppression according to CNS antiretroviral drug penetration in comparison with 67 patients on their first ART line. Cognitive performance (Trailmaking A, B, Digit Symbol, Grooved Pegboard; demographically adjusted and converted to Z scores, NPZ4) was evaluated, and CNS penetration effectiveness (CPE) ranks of 1 to 4 were assigned and summed per regimen. After a median of 173.2 months on therapy (1,909.3 patients-year), the rate of NCI was similar in both groups (mean NPZ4, -0.24 vs -0.2). Pretreated patients received regimens with a CPE <7 in a large proportion (30 vs 9 %; p < 0.01). Patients in monotherapy had worse NPZ4 score than patients receiving triple therapy (-0.78 vs -0.18; p = 0.02; effect sizes 1.38), and a lower CPE score was observed in patients with a CD4+ count nadir <200 cells/ml with NCI (6.5 vs 7.3, p = 0.04). In the multivariate model, only the lowest CD4+ count and hepatitis C virus coinfection were associated with NPZ4, whereas CPE <7 showed a trend to association (p = 0.06) probably due to patients on monotherapy (estimate -0.33, p < 0.01). In conclusion, the rate of NCI in largely pretreated patients was similar to that observed in patients on their first regimen, and nadir CD4+ count continue to be critical. CNS drug penetration should be considered in cases of high risk for NCI.

[Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients]. / Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por el virus de la inmunodeficiencia humana.

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.

Increased Natural Killer (NK)-cell cytotoxicity and Trypanosoma cruzi-specific memory B cells in subjects with discordant serology for Chagas disease.

The presence of memory T cell specific for Trypanosoma cruzi in subjects with discordant serology for Chagas disease supports a cleared infection in these subjects. Using high-dimensional flow cytometry, ELISPOT assays and quantitative PCR, antibody-secreting cells and memory B cells specific for T. cruzi, total B-cell phenotypes, innate immune responses and parasite DNA were evaluated in serodiscordant, seropositive and seronegative subjects for T. cruzi infection. T. cruzi-specific memory B cells but no antibody-secreting cells specific for T. cruzi, increased proportion of nonclassical monocytes and increased levels of polyfunctional NK cells were found in serodiscordant compared with seropositive subjects. None of the serodiscordant subjects evaluated showed detectable parasite DNA, most of them did not show cardiac abnormalities and a group of them had had confirmed positive serology for Chagas disease. The unique immune profiles in serodiscordant subjects support that T. cruzi infection was cleared or profoundly controlled in these subjects.

Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes.

OBJECTIVES: Limited data are available on resistance to etravirine, rilpivirine, darunavir and tipranavir in patients infected with HIV-1 non-B subtypes, in which natural polymorphisms at certain positions could influence the barrier and/or pathways to drug resistance. METHODS: FASTA format sequences from the reverse transcriptase and protease genes recorded within the Spanish Drug Resistance database (ResRIS) were examined. RESULTS: From 8272 genotypes derived from 5930 different HIV-1 patients included in ResRIS, 5276 genotypes had complete treatment information. Overall, 85% were from antiretroviral-experienced subjects and 7.5% belonged to HIV-1 non-B subtypes: CRF02_AG, C, F and G being the most prevalent variants. For etravirine, only G190A was more prevalent in B than non-B subtypes, whereas V90I and V179E were more frequent in non-B than B subtypes. For rilpivirine, V108I and Y188I were more frequent in B than non-B subtypes, whereas V90I was more prevalent in non-B subtypes. Despite these differences, the overall prevalence of resistance did not differ significantly when comparing etravirine or rilpivirine in B versus non-B subtypes (11.3% versus 7.4%, P = 0.13, and 10.5% versus 7.4%, P = 0.23, respectively). Despite more frequent natural polymorphisms in non-B than B subtypes at tipranavir resistance positions, the prevalence of tipranavir resistance was greater in B than non-B subtypes (11% versus 4.3%, P = 0.004), reflecting a greater antiretroviral exposure in the former. Darunavir resistance did not differ significantly when comparing B and non-B subtypes (5.8% versus 5.5%, P = 0.998). CONCLUSIONS: The rate of resistance to the most recently approved protease and non-nucleoside reverse transcriptase inhibitors is low in antiretroviral-experienced patients, regardless of the HIV-1 subtype.

Lipid-lowering effect and efficacy after switching to etravirine in HIV-infected patients with intolerance to suppressive HAART.

PURPOSE: Etravirine (ETR) has shown a good lipid profile in previous studies. The aim of this study was to determine the virologic, immunologic, and lipid outcome in HIV-infected patients switching to an ETR-based antiretroviral regimen due to intolerance or toxicity. METHODS: Observational cohort study of 125 HIV-infected patients who switched therapy to an ETR-based regimen. The lipid profile, including total triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was compared after 24 weeks. RESULTS: Patients changed from efavirenz (n = 34; 28%) and ritonavir-boosted protease inhibitors (PI/r; 67 cases: 21 atazanavir, 21 lopinavir, 11 fosamprenavir, 14 darunavir). Hyperlipidemia was the cause in only 22 patients (18%). At 24 weeks, a significant decrease was observed in mean TC level (-8%), LDL-C (-8%), TC:HDL ratio (-6%), and TG level (-20%). For patients receiving previously efavirenz, there was a significant reduction in TC (-23 mg/dL; -13%) and LDL-C (-25 mg/dL; -21%) levels and a trend to a better TG level (-38 mg/dL; -21%;P = .06). In the case of prior PI/r therapy, there was also a significant reduction in TC (-14 mg/dL; -6%) and TG levels (-58 mg/dL; -16%), mostly in prior lopinavir- or fosamprenavir-based therapy (TC -15%; TG -53%). Median CD4+ count increased from 513 to 621 cells/µL (P = .03), and there were only 3 cases of virologic failure (2%). CONCLUSIONS: In patients switching to an ETR-containing regimen, there is a significant improvement of lipids and maintenance of immunologic and virologic response. This lipid-lowering effect was irrespective of the presence of previous hyperlipidemia and for patients receiving different antiretroviral drugs.

Social isolation in HIV-infected patients according to subjective patient assessment and DEXA-confirmed severity of lipodystrophy.

This study was designed to investigate the persistence of lipodystrophy (LD)-related social distress and isolation in HIV-infected patients in the current era, according to confirmatory dual energy X-ray absorptiometry (DEXA) measurements. Cross-sectional interview data were collected from 168 HIV-positive adult patients taking more than 2 years of antiretroviral therapy (133 cases with LD diagnosed a mean of 7.2 years before; 35 without LD, controls). Mean time of HIV infection was 16.2 years (2.1-27.3), and the mean time of exposure to highly active antiretroviral therapy of 11.7 years (2.1-21.1). The presence and severity of LD, confirmed by DEXA measurements, correlated with social isolation through a validated scale, including avoidance of social relationships, sex, work, or sport activities. In comparison with control patients, social distress was observed for patients having moderate body changes. The significant correlation between LD and social isolation was irrespective of age, CD4+ count, HIV RNA level, AIDS diagnosis, time of HIV infection, anxiety, or depressive symptoms. These results confirm that patient assessment of LD is correlated with whole-body DEXA scan, and they highlight the role of LD as an independent cause of social isolation even after years of the diagnosis.

Racial discrimination and depressive symptoms mediated by conversations about race among students of color.

Racial discrimination is associated with adverse mental health outcomes among Students of Color. In order to address racial tensions, it is important to consider students' dialogues about race. The current study tested whether having positive and negative conversations about one's ethnic-racial group mediated the relation between racial discrimination at T1 and depressive symptoms 5 months later at T2 among 94 college Students of Color. Findings indicated that greater racial discrimination at T1 was associated with more frequent negative conversations about race at T2 (b = .38, p = .00), which was, in turn, associated with greater depressive symptoms at T2 (b = 2.73, p = .04); this pathway demonstrated significant mediation. However, positive conversations about race was not a significant mediator in this association. The current study highlights the importance of focusing on racial conversations after racial discrimination in order to minimize adverse effects on mental health among Students of Color.

Cultural Socialization and Ethnic-Racial Identity Mediated by Positive and Negative Conversations about Race: Exploring Differences among Asian American, African American, Latinx, Multiracial, and White Students.

The current study examined associations between cultural socialization and ethnic-racial identity via positive and negative conversations about one's ethnicity/race. Ethnic-racial differences between Asian American, African American, Latinx, Multiracial, and White students were explored. College students 18-22 (M age = 18.46) participating in a university-wide study provided self-reports of childhood cultural socialization, engagement in conversations about ethnicity/race during college, and ethnic-racial identity. Cultural socialization was associated with more positive conversations about race, and, in turn, greater ethnic-racial identity exploration, resolution, and affirmation among all students. Additionally, among Multiracial and African American students, cultural socialization was associated with greater negative conversations about race and, in turn, less ethnic-racial identity affirmation. Although cultural socialization was not associated with negative conversations about race for Asian American, Latinx, or White students, the relation between greater negative conversations about race and less ethnic-racial identity affirmation was significant. Negative conversations about race also informed greater ethnic-racial identity exploration among all students, but was not associated with ethnic-racial identity resolution. The current study highlights the nuanced ways that childhood cultural socialization and conversations about one's ethnicity/race influence college students' ethnic-racial identity, both similarly and differently among Asian American, African American, Latinx, Multiracial, and White students. Two items created for the current study were used to assess positive and negative conversations about one's ethnicity/race in the past month. Response options for the positive conversation item ("In the past month, I had conversations with someone about something positive about my ethnic-racial group.") and negative conversation item ("In the past month, I had conversations with someone about something negative about my ethnic-racial group.") were scored using a 5-point Likert scale ranging from (1) Not at all to (5) Extremely or almost always. Higher scores indicated more frequent positive conversations and more frequent negative conversations, respectively. Initial support for the validity of the two items for positive and negative conversations about race has been provided by research with emerging adults (Delaney et al., in press).

Mixed T Helper1/T Helper2/T Cytotoxic Profile in Subjects with Chronic Chagas Disease with Hypersensitivity Reactions to Benznidazole.

Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events (n = 22) and compared with those without adverse events (n = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4+ and CD8+ T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4+ and CD8+ T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. IMPORTANCE This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.

HTLV-2 Enhances CD8+ T Cell-Mediated HIV-1 Inhibition and Reduces HIV-1 Integrated Proviral Load in People Living with HIV-1.

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.

Severe rhabdomyolysis due to rosuvastatin in a liver transplant subject with human immunodeficiency virus and immunosuppressive therapy-related dyslipidemia.

Statins are relatively safe first-line agents to use in the setting of dyslipidemia associated with immunosuppressive therapy in subjects undergoing liver transplantation, and also in HIV-infected patients with dyslipidemia due to antiretroviral drugs, especially ritonavir-boosted protease inhibitors. Rosuvastatin, a new statin, has demonstrated higher potency than previously released statins and is not extensively metabolized by the liver P450 system; therefore, the probability of deleterious pharmacokinetic interactions with commonly used immunosuppressants and antiretroviral drugs is reduced. We present the first case of severe rhabdomyolysis in a liver transplant patient receiving rosuvastatin for the treatment of immunosuppressive therapy-related grade IV dyslipidemia, an HIV-infected subject on protease inhibitor-sparing HAART, that resolved after rosuvastatin withdrawal, probably related to interactions between calcineurin inhibitors and hepatic rosuvastatin uptake transporters such as organic anion transporting polypeptides (OATPs).

Safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with advanced liver disease.

PURPOSE: There are few data about the safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with very advanced liver disease. METHOD: Prospective study of 60 HIV/HCV coinfected patients who underwent a liver biopsy and received a lopinavir-based regimen. The rate of hepatotoxiciy and plasma trough levels were determined in absence/presence of cirrhosis (25 cases), especially in 11 patients with Child-Pugh stage B-C. RESULTS: Overall, geometric mean level of lopi-navir was 7,109 ng/mL (interquartile range [IQR], 5,163-9,029), without differences according to cirrhosis (7,662; IQR, 5,165-10,442) or not (6,708; IQR, 5,524-8,526; P = .6). In 11 patients with Child-Pugh stage B-C, trough level was 9,640 ng/mL (IQR, 1,620-11,622 ng/mL), but there was a 99% interpatient variability (72 to 13,331 ng/mL). During a follow-up of 195.2 patient-years, there were 7 cases of hepatotox-icity, with an incidence of 3.39 episodes/100 patient-years (2.2 to 7.9). This incidence was higher in patients with Child-Pugh stage B-C (5.43 episodes/100 patient-years). There were no differences in lopinavir trough levels between patients with or without liver toxicity (7,100 vs 7,119 ng/mL; P = .9). CONCLUSION: The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver disease is low. However, lopinavir plasma trough levels are increased, and there is a high interpatient variability.

Implementation of a lung cancer screening initiative in HIV-infected subjects.

In this pilot program of low-dose computed tomography (LDCT) for the screening of lung cancer (LC) in a targeted population of people with HIV (PWH), its prevalence was 3.6%; the number needed to screen in order to detect one case of lung cancer was 28, clearly outweighing the risks associated with lung cancer screening. While data from additional cohorts with longitudinal measurements are needed, PWH are a target population for lung cancer screening with LDCT.

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.