Tenofovir-Containing Antiretroviral Therapy and Clinical Outcomes of SARS-CoV-2 Infection in People Living with HIV.

Tenofovir has been hypothesized to be effective against COVID-19 and is available as two prodrugs, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), both part of antiretroviral therapy (ART) regimens. People living with human immunodeficiency virus (PLWH) might be at higher risk for COVID-19 progression; however, information about the impact of tenofovir on COVID-19 clinical outcomes remains controversial. The COVIDARE is a prospective observational multicentric study in Argentina. PLWH with COVID-19 were enrolled from September 2020 to mid-June 2022. Patients were stratified according to baseline ART into those with tenofovir (TDF or TAF) and those without. Univariate and multivariate analyses were performed to evaluate the impact of tenofovir vs. non-tenofovir-containing regimens on major clinical outcomes. Of the 1155 subjects evaluated, 927 (80%) received tenofovir-based ART (79% TDF, 21% TAF) whilst the remaining population was under non-tenofovir regimens. The non-tenofovir group had older age and a higher prevalence of heart and kidney disease. Regarding the prevalence of symptomatic COVID-19, tomographic findings, hospitalization, and mortality, no differences were observed. The oxygen therapy requirement was higher in the non-tenofovir group. In the multivariate analyses, a first model with adjustment for viral load, CD4 T-cell count, and overall comorbidities showed that oxygen requirement was associated with non-tenofovir ART. In a second model with adjustment by chronic kidney disease, tenofovir exposure was not statistically significant.

Impact of the Early COVID-19 Pandemic on the Number of HIV Preexposure Prophylaxis Uses and the Proportion of Preexposure Prophylaxis Users Receiving Sexually Transmitted Infection Testing Services.

BACKGROUND: With the potential impact of the COVID-19 pandemic on HIV preexposure prophylaxis (PrEP) care management, we assessed the number of PrEP users and sexually transmitted infection (STI) testing-eligible PrEP users, STI testing rates, and prevalence between prepandemic (January 1, 2018-March 31, 2020) and early-pandemic (April 1, 2020-September 30, 2020) periods. METHODS: In this retrospective cohort study, a PrEP user for a given quarter is defined as either a previous PrEP user or a PrEP initiator who has at least 1-day coverage of tenofovir/emtricitabine in the given quarter. The STI testing-eligible PrEP users for a given quarter were defined as those persons whose runout date (previous dispense date + days of tenofovir/emtricitabine supply) was in the given quarter. RESULTS: The quarterly number of PrEP users increased from the first quarter of 2018 to the first quarter of 2020 and then decreased in the second and third quarter of 2020. Among STI testing-eligible PrEP users who had ≤14 days between runout and next refill date, gonorrhea and chlamydia screening testing rates were 95.1% for prepandemic and 93.4% for early pandemic ( P = 0.1011). Among all STI testing-eligible PrEP users who were tested for gonorrhea and chlamydia, gonorrhea prevalence was 6.7% for prepandemic and 5.7% for early pandemic ( P = 0.3096), and chlamydia prevalence was 7.0% for prepandemic and 5.8% for early pandemic ( P = 0.2158). CONCLUSIONS: Although the early COVID-19 pandemic resulted in lower numbers of PrEP users and PrEP initiators, individuals who remained continuous users of PrEP maintained extremely high rates of bacterial STI screening. With high STI prevalence among PrEP users, assessments of PrEP care management are continuously needed.

Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout.

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. METHODS: Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). RESULTS: Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). CONCLUSIONS: Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH.

Viral hepatitis in persons living with HIV in the post-COVID era.

Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.

Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B.

BACKGROUND AND AIMS: HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). METHODS: Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. RESULTS: Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04-0.67, p = 0.01). CONCLUSION: Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.

Polyarteritis nodosa presenting with posterior reversible leukoencephalopathy syndrome.

A man in his 20s presented following a generalised tonic-clonic seizure on a background of a recent diagnosis of hepatitis B (HBV). During admission, he was severely hypertensive and imaging findings confirmed a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES). The patient subsequently developed multiorgan involvement with an axonal sensorimotor neuropathy, vascular cutaneous lesions and multiple bilateral renal and splenic infarcts. Based on the 2012 Revised International Chapel Hill Consensus Criteria, a diagnosis of polyarteritis nodosa (PAN) with secondary PRES was made. The patient was given intravenous methylprednisolone, followed by a prolonged course of oral prednisolone, and tenofovir antiviral therapy to target HBV seroconversion. He made a good neurological recovery with resolution of imaging changes. This case highlights the importance of a low threshold for systemic screening for young patients presenting with PRES secondary to uncontrolled hypertension and the importance of viral screening, particularly for HBV.

Treatment-Experienced Patients on Third-Line Therapy: A Retrospective Cohort of Treatment Outcomes at the HIV Advanced Treatment Centre, University Teaching Hospital, Zambia.

Antiretroviral therapy (ART) uptake continues to increase across sub-Saharan Africa and emergence of drug-resistant HIV mutations poses significant challenges to management of treatment-experienced patients with virologic failure. In Zambia, new third-line ART (TLART) guidelines including use of dolutegravir (DTG) were introduced in 2018. We assessed virologic suppression, immunologic response, and HIV drug-resistant mutations (DRMs) among patients on TLART at the University Teaching Hospital (UTH) in Lusaka, Zambia. We conducted a retrospective review of patients enrolled at UTH on TLART for >6 months between January 2010 and June 30, 2021. CD4 and HIV viral load (VL) at TLART initiation and post-initiation were assessed to determine virologic and immunologic outcomes. Regression analysis using bivariate and multivariate methods to describe baseline characteristics, virologic, and immunologic response to TLART was performed. A total of 345 patients met inclusion criteria; women comprised 57.6% (199/345) of the cohort. Median age at HIV diagnosis was 30 (interquartile range: 17.3-36.8). In 255 (73.8%) patients with at least two VLs, VL decreased from mean of 3.45 log10 copies/mL (standard deviation [SD]: 2.02) to 1.68 log10 copies/mL (SD: 1.79). Common ARVs prescribed included DTG (89.9%), tenofovir disoproxil fumarate (68.7%), and darunavir boosted with ritonavir (66.4%); 170 (49.3%) patients had genotypes; mutations consisted of 88.8% nucleoside reverse transcriptase inhibitor, 86.5% non-nucleoside reverse transcriptase inhibitor, and 55.9% protease inhibitor. VL suppression to <1,000 copies/mL was achieved in 225 (78.9%) patients. DRM frequency ranged from 56% to 89% depending on drug class. Treatment-experienced patients receiving TLART in Zambia achieved high rates of suppression despite high proportions of HIV mutations illustrating TLART effectiveness in the DTG era.

Case of organising pneumonia in HIV infection.

A man in his 50s presented to his doctor with a fever, sore throat, cough, dysgeusia and dyspnoea of several days' duration. Tests for HIV antigen, HIV antibody and HIV PCR were positive. He was referred to our hospital for initiation of antiretroviral therapy and bronchoscopy to clarify the cause of an abnormal lung shadow on chest CT. He was diagnosed with organising pneumonia, with concurrent HIV infection. His pulmonary lesions were remitted spontaneously, and he was administered a fixed-dose combination of tenofovir (50 mg), emtricitabine (200 mg) and bictegravir (25 mg) for HIV. This is a rare report of organising pneumonia with HIV infection. Physicians need to consider organising pneumonia when lung opacity is observed in a patient with HIV infection.

Tenofovir disoproxil fumarate/emtricitabine and severity of coronavirus disease 2019 in people with HIV infection.

BACKGROUND: Effective, safe, and affordable antivirals are needed for coronavirus disease 2019 (COVID-19). Several lines of research suggest that tenofovir may be effective against COVID-19, but no large-scale human studies with appropriate adjustment for comorbidities have been conducted. METHODS: We studied HIV-positive individuals on antiretroviral therapy (ART) in 2020 at 69 HIV clinics in Spain. We collected data on sociodemographics, ART, CD4+ cell count, HIV-RNA viral-load, comorbidities and the following outcomes: laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, intensive care unit (ICU) admission and death. We compared the 48-week risks for individuals receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and other regimes. All estimates were adjusted for clinical and sociodemographic characteristics via inverse probability weighting. RESULTS: Of 51 558 eligible individuals, 39.6% were on TAF/FTC, 11.9% on TDF/FTC, 26.6% on ABC/3TC, 21.8% on other regimes. There were 2402 documented SARS-CoV-2 infections (425 hospitalizations, 45 ICU admissions, 37 deaths). Compared with TAF/FTC, the estimated risk ratios (RR) (95% confidence interval) of hospitalization were 0.66 (0.43, 0.91) for TDF/FTC and 1.29 (1.02, 1.58) for ABC/3TC, the RRs of ICU admission were 0.28 (0.11, 0.90) for TDF/FTC and 1.39 (0.70, 2.80) for ABC/3TC, and the RRs of death were 0.37 (0.23, 1.90) for TDF/FTC and 2.02 (0.88-6.12) for ABC/3TC. The corresponding RRs of hospitalization for TDF/FTC were 0.49 (0.24, 0.81) in individuals ≥50 years and 1.15 (0.59, 1.93) in younger individuals. DISCUSSION: Compared with other antiretrovirals, TDF/FTC lowers COVID-19 severity among HIV-positive individuals with virological control. This protective effect may be restricted to individuals aged 50 years and older.

Tenofovir disoproxil fumarate and coronavirus disease 2019 outcomes in men with HIV.

OBJECTIVE: To compare the risk of coronavirus disease 2019 (COVID-19) outcomes by antiretroviral therapy (ART) regimens among men with HIV. DESIGN: We included men with HIV on ART in the Veterans Aging Cohort Study who, between February 2020 and October 2021, were 18 years or older and had adequate virological control, CD4 + cell count, and HIV viral load measured in the previous 12 months, and no previous COVID-19 diagnosis or vaccination. METHODS: We compared the adjusted risks of documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19-related hospitalization, and intensive care unit (ICU) admission by baseline ART regimen: tenofovir alafenamide (TAF)/emtricitabine (FTC), tenofovir disoproxil fumarate (TDF)/FTC, abacavir (ABC)/lamivudine (3TC), and other. We fit pooled logistic regressions to estimate the 18-month risks standardized by demographic and clinical factors. RESULTS: Among 20 494 eligible individuals, the baseline characteristics were similar across regimens, except that TDF/FTC and TAF/FTC had lower prevalences of chronic kidney disease and estimated glomerular filtration rate <60 ml/min. Compared with TAF/FTC, the estimated 18-month risk ratio (95% confidence interval) of documented SARS-CoV-2 infection was 0.65 (0.43, 0.89) for TDF/FTC, 1.00 (0.85, 1.18) for ABC/3TC, and 0.87 (0.70, 1.04) for others. The corresponding risk ratios for COVID-19 hospitalization were 0.43 (0.07, 0.87), 1.09 (0.79, 1.48), and 1.21 (0.88, 1.62). The risk of COVID-19 ICU admission was lowest for TDF/FTC, but the estimates were imprecise. CONCLUSION: Our study suggests that, in men living with HIV, TDF/FTC may protect against COVID-19-related events. Randomized trials are needed to investigate the effectiveness of TDF as prophylaxis for, and early treatment of, COVID-19 in the general population.

The Nucleoside/Nucleotide Analogs Tenofovir and Emtricitabine Are Inactive against SARS-CoV-2.

The urgent response to the COVID-19 pandemic required accelerated evaluation of many approved drugs as potential antiviral agents against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using cell-based, biochemical, and modeling approaches, we studied the approved HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTIs) tenofovir (TFV) and emtricitabine (FTC), as well as prodrugs tenofovir alafenamide (TAF) and tenofovir disoproxilfumarate (TDF) for their antiviral effect against SARS-CoV-2. A comprehensive set of in vitro data indicates that TFV, TAF, TDF, and FTC are inactive against SARS-CoV-2. None of the NRTIs showed antiviral activity in SARS-CoV-2 infected A549-hACE2 cells or in primary normal human lung bronchial epithelial (NHBE) cells at concentrations up to 50 µM TAF, TDF, FTC, or 500 µM TFV. These results are corroborated by the low incorporation efficiency of respective NTP analogs by the SARS-CoV-2 RNA-dependent-RNA polymerase (RdRp), and lack of the RdRp inhibition. Structural modeling further demonstrated poor fitting of these NRTI active metabolites at the SARS-CoV-2 RdRp active site. Our data indicate that the HIV-1 NRTIs are unlikely direct-antivirals against SARS-CoV-2, and clinicians and researchers should exercise caution when exploring ideas of using these and other NRTIs to treat or prevent COVID-19.

Impact of tenofovir on SARS-CoV-2 infection and severe outcomes among people living with HIV: a propensity score-matched study.

BACKGROUND: Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. OBJECTIVES: We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). METHODS: We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. RESULTS: After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78-1.04] or hospitalization (aOR 0.93; 95% CI, 0.60-1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or hospitalization (aOR 0.51; 95% CI, 0.15-1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10-1.07) compared with TAF/FTC. CONCLUSIONS: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.

Oral pre-exposure prophylaxis preference, uptake, adherence and continuation among adolescent girls and young women in Kampala, Uganda: a prospective cohort study.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) has been scaled up; however, data from real-world settings are limited. We studied oral PrEP preference, uptake, adherence and continuation among adolescent girls and young women (AGYW) vulnerable to HIV in sub-Saharan Africa. METHODS: We conducted a prospective cohort study among 14- to 24-year-old AGYW without HIV who were followed for 12 months in Kampala, Uganda. Within at least 14 days of enrolment, they received two education sessions, including demonstrations on five biomedical interventions that are; available (oral PrEP), will be available soon (long-acting injectable PrEP and anti-retroviral vaginal ring) and in development (PrEP implant and HIV vaccine). Information included mode and frequency of delivery, potential side effects and method availability. Volunteers ranked interventions, 1 = most preferred to 5 = least preferred. Oral PrEP was "preferred" if ranked among the top two choices. All were offered oral PrEP, and determinants of uptake assessed using Poisson regression with robust error variance. Adherence was assessed using plasma tenofovir levels and self-reports. RESULTS: Between January and October 2019, 532 volunteers were screened; 285 enrolled of whom 265 received two education sessions. Mean age was 20 years (SD±2.2), 92.8% reported paid sex, 20.4% reported ≥10 sexual partners in the past 3 months, 38.5% used hormonal contraceptives, 26.9% had chlamydia, gonorrhoea and/or active syphilis. Of 265 volunteers, 47.6% preferred oral PrEP. Willingness to take PrEP was 90.2%; however, uptake was 30.6% (n = 81). Following enrolment, 51.9% started PrEP on day 14 (same day PrEP offered), 20.9% within 30 days and 27.2% after 30 days. PrEP uptake was associated with more sexual partners in the past 3 months: 2-9 partners (aRR = 2.36, 95% CI: 1.20-4.63) and ≥10 partners (aRR 4.70, 95% CI 2.41-9.17); oral PrEP preference (aRR 1.53, 95% CI 1.08-2.19) and being separated (aRR 1.55, 95% CI 1.04-2.33). Of 100 samples from 49 volunteers during follow up, 19 had quantifiable tenofovir levels (>10 µg/L) of which only three were protective (>40 µg/L). CONCLUSIONS: Half of AGYW preferred oral PrEP, uptake and adherence were low, uptake was associated with sexual behavioural risk and oral PrEP preference. Development of alternative biomedical products should be expedited to meet end-user preferences and, community delivery promoted during restricted movement.

Safety of Tenofovir Disoproxil Fumarate for Pregnant Women Facing the Coronavirus Disease 2019 Pandemic.

We assessed the teratogenicity of tenofovir, a human immunodeficiency virus (HIV) drug similar to remdesivir that is currently being evaluated for the treatment of coronavirus disease 2019 (COVID-19). Using US Medicaid Analytic eXtract (MAX) claims data (2000-2014), we identified a population-based pregnancy cohort of women with HIV who filled at least 1 prescription for antiretroviral therapies (ART) during the first trimester. Women on tenofovir disoproxil fumarate (TDF) were compared with women receiving ART without TDF. Major malformations were identified by International Classification of Diseases, Ninth Revision, codes using validated algorithms. Relative risks and 95% confidence intervals were estimated using propensity score stratification to control for potential confounders. We incorporated the results into prior knowledge by conducting a systematic literature review and a meta-analysis. Major congenital malformations were diagnosed in 37 out of 866 (4.27%) infants exposed to TDF and 38 out of 1,020 (3.73%) infants exposed to ART other than TDF; the adjusted relative risk was 1.21 (95% confidence interval: 0.77, 1.90). Estimates for specific malformations were imprecise. The pooled relative risk from the meta-analysis with 6 prior studies was 0.88 (95% confidence interval: 0.75, 1.03). Based on evidence accumulated in patients with HIV, first-trimester TDF use does not increase the risk of major congenital malformations overall in the newborn compared with other ART.

Association between chronic hepatitis B infection and COVID-19 outcomes: A Korean nationwide cohort study.

BACKGROUND/AIMS: We measured the association between underlying chronic hepatitis B (CHB) and antiviral use with infection rates among patients who underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. METHODS: In total, 204,418 patients who were tested for SARS-CoV-2 between January and June 2020 were included. For each case patient (n = 7,723) with a positive SARS-CoV-2 test, random controls (n = 46,231) were selected from the target population who had been exposed to someone with coronavirus disease 2019 (COVID-19) but had a negative SARS-CoV-2 test result. We merged claim-based data from the Korean National Health Insurance Service database collected. Primary endpoints were SARS-CoV-2 infection and severe clinical outcomes of COVID-19. RESULTS: The proportion of underlying CHB was lower in COVID-19 positive patients (n = 267, 3.5%) than in COVID-19 negative controls (n = 2482, 5.4%). Underlying CHB was associated with a lower SARS-CoV-2 positivity rate, after adjusting for comorbidities (adjusted odds ratio [aOR] 0.65; 95% confidence interval [CI], 0.57-0.74). Among patients with confirmed COVID-19, underlying CHB tended to confer a 66% greater risk of severe clinical outcomes of COVID-19, although this value was statistically insignificant. Antiviral treatment including tenofovir and entecavir was associated with a reduced SARS-CoV-2 positivity rate (aOR 0.49; 95% CI, 0.37-0.66), while treatment was not associated with severe clinical outcomes of COVID-19. CONCLUSIONS: Underlying CHB and antiviral agents including tenofovir decreased susceptibility to SARS-CoV-2 infection. HBV coinfection did not increase the risk of disease severity or lead to a worse prognosis in COVID-19.