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1.
Viruses ; 15(5)2023 05 09.
Article in English | MEDLINE | ID: covidwho-20242115

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , HIV-1 , Humans , Tenofovir/therapeutic use , Tenofovir/pharmacology , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/pharmacology , SARS-CoV-2 , HIV Infections/complications , HIV Infections/drug therapy
2.
Sex Transm Dis ; 50(5): 304-309, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2303267

ABSTRACT

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.


Subject(s)
COVID-19 , Gonorrhea , HIV Infections , Pre-Exposure Prophylaxis , Sexually Transmitted Diseases , Male , Humans , Gonorrhea/diagnosis , Gonorrhea/epidemiology , Gonorrhea/drug therapy , Pandemics/prevention & control , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/prevention & control , Retrospective Studies , Homosexuality, Male , COVID-19/epidemiology , COVID-19/prevention & control , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Tenofovir/therapeutic use , Emtricitabine , Pre-Exposure Prophylaxis/methods
4.
Ann Intern Med ; 176(4): 556-560, 2023 04.
Article in English | MEDLINE | ID: covidwho-2262725

ABSTRACT

Remdesivir and molnupiravir were the only 2 repurposed antivirals that were approved for emergency use during the COVID-19 pandemic. Both drugs received their emergency use authorization on the basis of a single industry-funded phase 3 trial, which was launched after evidence of in vitro activity against SARS-CoV-2. In contrast, for tenofovir disoproxil fumarate (TDF), little in vitro evidence was generated, no randomized trials for early treatment were done, and the drug was not considered for authorization. Yet, by the summer of 2020, observational evidence suggested a substantially lower risk for severe COVID-19 in TDF users compared with nonusers. The decision-making process for the launching of randomized trials for these 3 drugs is reviewed. Observational data in favor of TDF was systematically dismissed, even though no viable alternative explanations were proposed for the lower risk for severe COVID-19 among TDF users. Lessons learned from the TDF example during the first 2 years of the COVID-19 pandemic are described, and the use of observational clinical data to guide decisions about the launch of randomized trials during the next public health emergency is proposed. The goal is that gatekeepers of randomized trials make better use of the available observational evidence for the repurposing of drugs without commercial value.


Subject(s)
Antiviral Agents , COVID-19 , Humans , Antiviral Agents/therapeutic use , Drug Repositioning , SARS-CoV-2 , Pandemics , Tenofovir
5.
AIDS Rev ; 25(1): 1-13, 2023.
Article in English | MEDLINE | ID: covidwho-2282191

ABSTRACT

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.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Coinfection , Drug Users , HIV Infections , Hepatitis A , Hepatitis B, Chronic , Hepatitis B , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Sexual and Gender Minorities , Substance Abuse, Intravenous , Male , Humans , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Hepatitis B, Chronic/complications , Homosexuality, Male , Coinfection/drug therapy , Coinfection/epidemiology , Coinfection/complications , Substance Abuse, Intravenous/complications , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , COVID-19/complications , Hepatitis C, Chronic/complications , Hepatitis C/drug therapy , Liver Cirrhosis/complications , Tenofovir/therapeutic use , Hepatitis B/drug therapy
6.
Clin Infect Dis ; 76(10): 1727-1734, 2023 05 24.
Article in English | MEDLINE | ID: covidwho-2268136

ABSTRACT

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.


Subject(s)
COVID-19 , HIV Infections , Humans , United States/epidemiology , COVID-19/epidemiology , COVID-19/complications , Tenofovir/therapeutic use , COVID-19 Vaccines , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV
7.
Dig Dis Sci ; 68(6): 2731-2737, 2023 06.
Article in English | MEDLINE | ID: covidwho-2233073

ABSTRACT

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.


Subject(s)
COVID-19 , Hepatitis B, Chronic , Adult , Humans , Tenofovir/therapeutic use , Antiviral Agents/therapeutic use , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Treatment Outcome , COVID-19/complications , SARS-CoV-2 , Retrospective Studies
8.
AIDS Res Hum Retroviruses ; 39(4): 204-210, 2023 04.
Article in English | MEDLINE | ID: covidwho-2212672

ABSTRACT

Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri- and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri- and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Humans , Female , Middle Aged , HIV Infections/complications , HIV Infections/drug therapy , Bone Density , Anti-HIV Agents/adverse effects , Tenofovir/adverse effects , Pandemics , Perimenopause , Adenine/pharmacology , Aging
9.
BMJ Case Rep ; 15(8)2022 Aug 31.
Article in English | MEDLINE | ID: covidwho-2193658

ABSTRACT

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.


Subject(s)
Polyarteritis Nodosa , Posterior Leukoencephalopathy Syndrome , Antiviral Agents/therapeutic use , Humans , Male , Methylprednisolone/therapeutic use , Polyarteritis Nodosa/complications , Polyarteritis Nodosa/diagnosis , Polyarteritis Nodosa/drug therapy , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Posterior Leukoencephalopathy Syndrome/drug therapy , Tenofovir/therapeutic use
10.
AIDS Res Hum Retroviruses ; 38(10): 798-805, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2151803

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Female , Male , Darunavir/therapeutic use , Anti-HIV Agents/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Retrospective Studies , Viral Load , Ritonavir/therapeutic use , Universities , Zambia , Tenofovir/therapeutic use , Treatment Outcome , Hospitals, Teaching , Protease Inhibitors/therapeutic use
12.
BMJ Case Rep ; 15(11)2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2137565

ABSTRACT

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.


Subject(s)
Cryptogenic Organizing Pneumonia , HIV Infections , Pneumonia , Male , Humans , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/diagnosis , Emtricitabine/therapeutic use , Tenofovir/therapeutic use , Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/drug therapy
13.
Ann Intern Med ; 173(7): 536-541, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-2110869

ABSTRACT

BACKGROUND: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations. OBJECTIVE: To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART. DESIGN: Cohort study. SETTING: HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020. PARTICIPANTS: 77 590 HIV-positive persons receiving ART. MEASUREMENTS: Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models. RESULTS: Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died. LIMITATION: Residual confounding by comorbid conditions cannot be completely excluded. CONCLUSION: HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV. PRIMARY FUNDING SOURCE: Instituto de Salud Carlos III and National Institutes of Health.


Subject(s)
Antiretroviral Therapy, Highly Active , Coronavirus Infections/epidemiology , HIV Infections/drug therapy , Pneumonia, Viral/epidemiology , Adenine/analogs & derivatives , Adult , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Dideoxynucleosides , Drug Combinations , Emtricitabine , Female , HIV Infections/mortality , Hospitalization/statistics & numerical data , Humans , Incidence , Intensive Care Units/statistics & numerical data , Lamivudine , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiology , Tenofovir
14.
AIDS ; 36(15): 2171-2179, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2115651

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Humans , Middle Aged , Aged , Emtricitabine/therapeutic use , Lamivudine/therapeutic use , Tenofovir/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Antiretroviral Therapy, Highly Active , Anti-HIV Agents/therapeutic use , SARS-CoV-2 , Drug Combinations
15.
OMICS ; 26(11): 583-585, 2022 11.
Article in English | MEDLINE | ID: covidwho-2087720

ABSTRACT

The current pandemic has markedly shifted the focus of the global research and development ecosystem toward infectious agents such as SARS-CoV-2, the causative agent for COVID-19. A case in point is the chronic liver disease associated with hepatitis B virus (HBV) infection that continues to be a leading cause of severe liver disease and death globally. The burden of HBV infection is highest in the World Health Organization designated western Pacific and Africa regions. Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue used in treatment of HBV infection but carries a potential for kidney toxicity. TDF is not metabolized by the cytochrome P450 enzymes and, therefore, its clearance in the proximal tubule of the renal nephron is controlled mostly by membrane transport proteins. Clinical pharmacogenomics of TDF with a focus on drug transporters, discussed in this perspective article, offers a timely example where resource-limited countries and regions of the world with high prevalence of HBV can strengthen the collective efforts to fight both COVID-19 and liver diseases impacting public health. We argue that precision/personalized medicine is invaluable to guide this line of research inquiry. In all, our experience in Ghana tells us that it is important not to forget the burden of chronic diseases while advancing research on infectious diseases such as COVID-19. For the long game with COVID-19, we need to address the public health burden of infectious agents and chronic diseases in tandem.


Subject(s)
COVID-19 , Hepatitis B, Chronic , Hepatitis B , Humans , Tenofovir/adverse effects , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Pharmacogenetics , Ecosystem , Antiviral Agents/adverse effects , DNA, Viral/therapeutic use , SARS-CoV-2 , Hepatitis B/complications , Hepatitis B/genetics , Kidney , Ghana
16.
AIDS ; 36(12): 1689-1696, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-2018370

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Anti-HIV Agents/therapeutic use , COVID-19 Testing , Cohort Studies , Emtricitabine/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Humans , Lamivudine/therapeutic use , Male , SARS-CoV-2 , Tenofovir/therapeutic use
17.
Molecules ; 27(13)2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1917636

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , COVID-19 Drug Treatment , HIV Infections , HIV-1 , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Emtricitabine/pharmacology , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Humans , Nucleosides/pharmacology , Nucleosides/therapeutic use , Nucleotides/pharmacology , Pandemics , RNA, Viral , RNA-Dependent RNA Polymerase , SARS-CoV-2 , Tenofovir/pharmacology , Tenofovir/therapeutic use
18.
J Antimicrob Chemother ; 77(8): 2265-2273, 2022 07 28.
Article in English | MEDLINE | ID: covidwho-1890951

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Anti-HIV Agents/therapeutic use , COVID-19 Testing , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Humans , Lamivudine/therapeutic use , Propensity Score , Prospective Studies , SARS-CoV-2 , Tenofovir/therapeutic use
19.
J Int AIDS Soc ; 25(5): e25909, 2022 05.
Article in English | MEDLINE | ID: covidwho-1885412

ABSTRACT

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.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Adolescent , Adult , Anti-HIV Agents/therapeutic use , Female , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Prospective Studies , Tenofovir/therapeutic use , Uganda , Young Adult
20.
Am J Health Syst Pharm ; 79(16): 1330-1336, 2022 08 05.
Article in English | MEDLINE | ID: covidwho-1830999

ABSTRACT

PURPOSE: To describe a case of increased viral load in a patient with HIV-1 infection receiving treatment with crushed bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF). SUMMARY: A 43-year-old man, newly diagnosed with HIV, was hospitalized due to failure to thrive, neurological changes, and hypotension. Before treatment, the HIV viral load (VL) was 769,704 copies/mL and the CD4+ T-cell count was 36 cells/µL. On hospital day (HD) 8, B/FTC/TAF by mouth daily was initiated. During the hospitalization, the patient's course was complicated by opportunistic infections, bilateral pneumothorax, seizure activity, and acute respiratory distress, requiring multiple intubations and extended time in the intensive care unit. A repeat VL measurement on HD 28 was 5,887 copies/mL after the patient had received 14 of 20 scheduled B/FTC/TAF doses. Because of a failed swallow study and continued nutritional deficits, a percutaneous endoscopic gastrostomy (PEG) tube was placed on HD 38 and continuous tube feeds via the PEG tube were initiated. Subsequently, the B/FTC/TAF order was modified to be crushed, mixed in 30 mL water, and administered daily via the PEG tube. A repeat VL measurement on HD 65 showed an increase to 8,047 copies/mL, despite receipt of 37 consecutive doses of B/FTC/TAF. B/FTC/TAF was discontinued and dolutegravir 50 mg twice daily, darunavir 800 mg plus ritonavir 100 mg (DRV/r), and tenofovir disoproxil fumarate/FTC 300 mg/200 mg were started due to virological increase, need for a viable option compatible with PEG tube delivery, and potential for integrase inhibitor resistance. At the time of regimen change (HD 67), a resistance panel showed minor mutations, E157Q and V118I. The regimen was streamlined with discontinuation of DRV/r on HD 92. The patient was discharged on HD 161. The PEG tube was removed 2 months after discharge, oral B/FTC/TAF was reinitiated, and the patient was virologically suppressed at 1 year after discharge. CONCLUSION: Controlled studies are needed to verify acceptable pharmacokinetic and pharmacodynamic metrics for crushed B/FTC/TAF given via tube, with and without tube feeds, before use in this manner.


Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Adenine , Adult , Alanine , Amides , Drug Combinations , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Humans , Male , Piperazines , Pyridones/therapeutic use , Tenofovir/analogs & derivatives , Viral Load
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