Investigational drugs with dual activity against HBV and HIV (Review)

Abstract

Chronic hepatitis B (CHB) and acquired immunodeficiency syndrome (AIDS) are global public health problems that pose a significant health burden. Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is common, as these viruses have similar transmission routes, such as blood transmission, sexual transmission and mother-to-child transmission. Coinfection frequently leads to accelerated disease progression. For individuals coinfected with HIV/HBV, combination antiretroviral therapy containing dual anti-HBV drugs is recommended. Certain studies have also indicated the benefits of antiretroviral drugs with anti-HBV activity in patients with coinfection. A total of four Food and Drug Administration-approved HIV drugs also have anti-HBV activity; namely, emtricitabine, lamivudine, tenofovir disoproxil fumarate and tenofovir alafenamide, which are all nucleoside reverse transcriptase inhibitors. However, various issues, including drug resistance and side effects, limit their application. Therefore, it is necessary to develop more drugs with dual activity against HBV and HIV. The present review outlines the mechanisms, safety and efficacy of certain drugs that have been investigated for this purpose.

Tenofovir, Another Inexpensive, Well-Known and Widely Available Old Drug Repurposed for SARS-COV-2 Infection

“…Moreover, their use can induce HIV resistance in patients with no known HIV-infection. TDF is a generic, inexpensive, well-known and widely available drug that is currently used for HIV and HBV treatment and for HIV prophylaxis [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 72 ]. It has good pharmacological characteristics with long serum and intracellular half-life, few adverse effects and drug–drug interactions and is orally administered [ 110 ].…”

“…TDF and TAF are also extensively and efficaciously used as pre-exposure prophylaxis (PrEP) against HIV infection in people at risk of acquiring this infection [ 57 , 58 , 59 , 60 , 61 ]. The current first line therapies for chronic HBV infection also includes TDF and TAF, which have proven to be well-tolerated and also highly effective in preventing liver fibrosis progression [ 62 , 63 , 64 ]. Further, tenofovir has been proposed to reduce the risk of herpes simplex virus 1 and 2 (HSV-1, HSV-2) infections, although studies have shown conflicting results [ 65 , 66 , 67 , 68 ].…”

The Application of Prodrugs as a Tool to Enhance the Properties of Nucleoside Reverse Transcriptase Inhibitors

“…No cytotoxic effects were observed up to the high-tested concentration of 1000 nM. It also showed activity against HIV-2 in PBMCs (mean EC 50 ± SD = 3.5 ± 1.5) and against six HIV-1 isolates in MDMs (mean EC 50 ± SD = 2.5 ± 1.7 nM) [57]. Human PBMCs were used to evaluate the relative levels of TFV-PP produced by (10) and TFV.…”

“…No antagonistic interactions were recorded between (10) and any FDA-approved antiretroviral drug, such as NRTI. Thus, the prodrug could deliver high levels of the active metabolite and reduce toxicity [57].…”