Emtricitabine 200mg / Tenofovir disoproxil 245mg tablets

BackgroundPharmacological treatments for COVID-19 remain limited, particularly for severe outcomes. Tenofovir, an inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), has been proposed as a therapeutic agent to reduce hospitalization, intensive care unit (ICU) admissions, and mortality.ObjectiveTo assess the efficacy of tenofovir in COVID-19 patients based on randomized controlled trials (RCTs).MethodsA systematic review of RCTs assessing tenofovir in COVID-19 was conducted. Searches in PubMed/MEDLINE, Scopus, Cochrane Library, LILACS, SciELO, and COVID-19 LOVE databases were last updated on April 16, 2025. Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. As a meta-analysis was not feasible, a qualitative analysis was performed. The review protocol was registered in PROSPERO (CRD42023465336).ResultsAmong 1241 retrieved trials, three met the inclusion criteria. These trials, conducted in 32 hospitals across Colombia, Spain and Iran included 1048 patients. In the Colombian study, the combination of tenofovir disoproxil/emtricitabine with colchicine and rosuvastatin was associated with reduced 28-day mortality (risk difference [RD] = -0.05; 95% CI: -0.07 to -0.04) and lower need for invasive mechanical ventilation (RD = -0.08; 95% CI: -0.11 to -0.04). However, randomization bias and small sample size limit the interpretation of these results. Conversely, the Spanish study was classified as having a low risk of bias, but found no significant benefit of tenofovir disoproxil/emtricitabine in reducing 28-day mortality (risk ratio [RR] = 1.76; 95% CI: 0.52 to 5.91) or for the composite outcome of ICU admission, disease progression, and mortality (RR = 0.95; 95% CI: 0.66 to 1.40). The Iranian study, in turn, demonstrated that tenofovir alafenamide, when combined with standard treatment, significantly reduced the need for mechanical ventilation (0.0% vs. 13.3%, p = 0.038) and ICU length of stay (3.3 days vs. 14.5 days; p = 0.04). However, the presence of a high risk of bias, with major concerns regarding co-interventions and statistical analyses, precludes a definitive conclusion regarding these results.ConclusionsThis review identified three clinical trials evaluating the efficacy of tenofovir in COVID-19, with conflicting results. One study suggested a potential benefit in reducing mortality and the need for invasive mechanical ventilation in mild to moderate cases but methodological limitations, including risk of bias and small sample size, weaken its conclusions. The second study found no significant impact on mortality or disease progression. In the third study, no deaths were reported, but he significant reduction in the need for mechanical ventilation and ICU length of stay is extremely limited due to the high risk of bias. Given these inconsistencies and the limitations of available evidence, tenofovir cannot be recommended for COVID-19 treatment.

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Human immunodeficiency virus (HIV) prevention has advanced substantially, yet ending new transmissions by 2030 remains uncertain. Pre-exposure prophylaxis (PrEP) has high biological efficacy, but real-world effectiveness varies due to adherence, access, and delivery barriers. This review aims to synthesize evidence on the efficacy of PrEP in reducing HIV incidence and to discuss its implications for achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2030 targets. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance, MEDLINE, Embase, Scopus, and Cochrane Library were searched for English-language studies published between January 2010 and January 2025 assessing PrEP efficacy in high-risk populations. Nine randomized controlled trials (RCTs) comprising more than 20,000 participants across multiple continents were included. Across oral tenofovir-based PrEP trials, risk reduction ranged from 49% to 86% in intention-to-treat (ITT) analyses, with markedly higher efficacy in adherence-defined subgroups (e.g., up to 92-99% in trials with pharmacokinetic confirmation). Long-acting injectable cabotegravir (CAB-LA) was superior to daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) in two large RCTs, with relative risk reduction up to 89% and high observed adherence consistent with clinic-based dosing. Adverse events were generally mild to moderate (gastrointestinal symptoms, headache), with expected renal marker changes in some oral PrEP trials and injection-site reactions for CAB-LA; no consistent evidence of risk compensation was observed. PrEP is highly effective when taken as prescribed, but achieving population-level impact aligned with UNAIDS targets requires scale-up, improved access, and interventions that support persistence and adherence, including expanded delivery models and longer-acting options.

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RationaleGlobally, there are 1.3 million new HIV infections annually, with a disproportionate burden on young women and girls, especially in sub-Saharan Africa (63% of new infections). Despite the demonstrated effectiveness of pre-exposure prophylaxis (PrEP), global uptake remains low, reaching only 16.5% of the UNAIDS 2025 target. PrEP adherence is suboptimal in vulnerable populations. There is an urgent need to develop and implement alternative, user-friendly PrEP strategies like long-acting formulations that minimise reliance on daily dosing or frequent injections. Lenacapavir is a first-in-class, long-acting capsid inhibitor that disrupts HIV replication at multiple stages. Following an oral loading dose, lenacapavir administered by subcutaneous injection provides six months of protection against HIV.ObjectivesTo evaluate the benefits and harms of long-acting injectable lenacapavir for HIV PrEP compared to oral fixed-dose combination PrEP (tenofovir disoproxil fumarate plus emtricitabine (F/TDF) and/or oral tenofovir alafenamide plus emtricitabine (F/TAF)), long-acting injectable cabotegravir (CAB-LA), or placebo or no prophylaxis.Search methodsWe searched CENTRAL, PubMed, and two trial registers and conducted reference checking to identify eligible studies. The search is current to May 2025.Eligibility criteriaWe included randomised controlled trials (RCTs) with no date or language restrictions in any HIV-negative person at risk of acquiring HIV through sexual contact or exposure to blood, comparing long-acting injectable lenacapavir with oral PrEP, long-acting injectable cabotegravir, placebo or no prophylaxis.OutcomesOur critical outcomes were: new HIV infections or relative risk of HIV infection; serious adverse events (SAEs); adverse events (AEs); adverse drug reactions: injection site reactions; and all-cause mortality. We included data at 26- and 52-week time points.Risk of biasWe used the Cochrane RoB 2 tool to assess risk of bias in the included studies.Synthesis methodsWe meta-analysed data for each outcome where possible, using the inverse variance statistical method with a random-effects model. We reported risk ratios (RR) with 95% confidence intervals (CIs) for dichotomous data. Where this was not possible, we synthesised results using the direction of effect, guided by the Synthesis Without Meta-analysis (SWiM) reporting guidelines. We used GRADE to assess the certainty of evidence.Included studiesWe included two studies with 8660 participants. The first trial, conducted in South Africa and Uganda, included adolescent girls and young women (16 to 25 years) and compared injectable lenacapavir with daily oral PrEP consisting of F/TAF in one comparator arm and F/TDF in the other. The second trial, conducted in the USA, Brazil, Thailand, South Africa, Peru, Argentina, and Mexico, included cisgender gay, bisexual and other men, transgender women, transgender men, and gender-nonbinary persons of any age who have condomless, receptive anal sex with partners assigned male at birth. It compared injectable lenacapavir with F/TDF. In both trials, participants in the lenacapavir group received placebo tablets that matched the oral PrEP, and participants in the oral PrEP group received placebo injections that matched lenacapavir.Synthesis of resultsNew HIV infections Lenacapavir results in a large reduction in new HIV infections at 52 weeks compared to oral PrEP (RR 0.07, 95% CI 0.02 to 0.22; 2 studies, 8660 participants; high-certainty evidence). There were 14 fewer new HIV infections per 1000 (ranging from 15 fewer to 12 fewer), with a number needed to treat for an additional beneficial outcome (NNTB) of 70. Serious adverse events Lenacapavir results in a slight reduction in SAEs at 52 weeks compared to oral PrEP (RR 0.78, 95% CI 0.61 to 0.99; 2 studies, 8660 participants; high-certainty evidence). There were 8 fewer SAEs per 1000 (ranging from 15 fewer to 0 fewer), NNTB of 128. Adverse events Lenacapavir results in little to no difference in AEs at 52 weeks compared to oral PrEP (RR 0.99, 95% CI 0.96 to 1.01; 2 studies, 8660 participants; high-certainty evidence). There were 8 fewer AEs per 1000 (ranging from 31 fewer to 8 more), NNTB of 55. Adverse drug reactions: injection site reactions Lenacapavir likely increases adverse drug reactions: injection site reactions compared to oral PrEP at 52 weeks (RR 1.68, 95% CI 1.20 to 2.33; 2 studies, 8660 participants; moderate-certainty evidence). There were 295 more adverse drug reactions per 1000 (ranging from 87 more to 577 more), number needed to treat for an additional harmful outcome of 4. All-cause mortality Lenacapavir results in little to no difference in all-cause mortality at 52 weeks compared to oral PrEP (RR 0.57, 95% CI 0.11 to 3.06; 2 studies, 8660 participants; high-certainty evidence). There were 1 fewer deaths per 1000 (ranging from 2 fewer to 4 more), NNTB of 1073. We rated all critical outcomes as low risk of bias in both studies. We found no difference on subgroup analysis between comparators F/TDF and F/TAF.Authors' conclusionsWhen compared to oral PrEP, lenacapavir results in a large reduction in new HIV infections at 52 weeks, with one HIV infection prevented for every 70 people receiving lenacapavir rather than oral PrEP, that is 14 fewer HIV infections per 1000 people treated with lenacapavir. Lenacapavir results in a slight reduction in SAEs and little to no difference in AEs compared to oral PrEP. Lenacapavir likely increases the risk of injection site reactions compared with oral PrEP, but discontinuation of lenacapavir in the included trials due to injection site reactions was rare. There is little to no difference in mortality between lenacapavir and oral PrEP. No studies compared lenacapavir to injectable long-acting cabotegravir, placebo or no prophylaxis. Within the included trials, there was a non-randomised comparison of lenacapavir with background HIV incidence in the screened population as a proxy for a no-PrEP arm. There was a large reduction in HIV incidence in the lenacapavir study arms compared to background HIV incidence in the screened populations.FundingThis Cochrane review was part-funded by the South African National Department of Health (NDoH) through the Evidence to Decision (E2D) Collaboration project. The E2D Collaboration is a partnership between the NDoH, the South African Medical Research Council, and Stellenbosch University (2024 to 2028). The views expressed in this review do not necessarily represent the views of the funder.RegistrationPROSPERO (2025) CRD420251080791.

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