An in vitro evaluation of drugs used in the Kenyan ART program.

Joseph Muriuki,Raphael Lihana,Joseph Mwangi,Raphael Lwembe,Matilu Mwau,Zipporah Ng’Ang’A

doi:10.11604/pamj.2016.23.134.7157

Abstract

The majority of anti-HIV drug susceptibility tests have been performed on subtype B HIV-1 strains, since these are the most prevalent in countries designing, testing, and manufacturing the current anti-HIV agents. The increasing global spread of HIV subtype highlights the need to determine the activity of anti-HIV drugs against subtypes of HIV other than subtype B. Furthermore an increasing number of individuals infected with many of the non subtype B virus strains now receive antiretroviral therapy because of rollout programs in developing countries as well as increasing migration to the developed world. The phenotypic susceptibility of two laboratory strains HIV-1JFRL and HIV-1IIIB (representing subtype B) and two clinical isolates HIV-104RTA and HIV-1025RTA (representing subtypes A and D respectively) was determined. The in vitro drug susceptibility testing of the isolates was carried out in C8166 cell line and in peripheral blood mononuclear cells (PBMCs). The study revealed that the drugs used in the Kenyan national ART program inhibited HIV-1 replication in-vitro as their inhibitory concentrations (IC50) compared well with the standard Inhibitory concentration values. The results also suggest a biochemical similarity of the reverse transcriptase (RT) and protease enzymes from these subtypes despite the divergence at the genetic level. The findings suggest that similar clinical benefits of antiviral therapy obtain in persons infected with other subtypes of HIV-1other than subtype B and that the generic drugs used in the national ART program in Kenya are as efficacious as branded drugs in inhibiting HIV replication in vitro despite the limited number of the viruses studied.

Highlights

Antiretroviral drug design, resistance research, and interpretation systems have been largely based on HIV-1 subtype B viruses, which have historically been the most prevalent subtype in North America, Western Europe and Australia even though subtype B viruses account for only about 12% of the worldwide HIV-1 infections
In this study we have shown that non-B subtype isolates of HIV-1 are similar in their drug susceptibility to subtype B isolates
These findings suggest that the five anti-HIV compounds used in this study retain their anti-HIV activity against HIV-1 viral strains other than subtype B and continue being useful for the treatment of persons infected with non-B HIV-1 subtypes

Summary

Introduction

Antiretroviral drug design, resistance research, and interpretation systems have been largely based on HIV-1 subtype B viruses, which have historically been the most prevalent subtype in North America, Western Europe and Australia even though subtype B viruses account for only about 12% of the worldwide HIV-1 infections. There are 6 classes of ARV agents with 25 drugs approved for single drug treatment and 12 as fixed dose combinations (FDCs) by the United States food and drugs administration US-FDA [4]. These drugs target 4 distinct proteins namely; host cell receptor, reverse transcriptase, integrase and protease to retard HIV replication. The target of NNRTIs is the same as NRTIs (viral reverse transcriptase) They inhibit HIV-1 RT by binding and inducing the formation of a hydrophobic pocket proximal to, but not overlapping the active site [5] Protease inhibitors (PIs) the third class of approved ARVs function by blocking proteolysis of the viral polyprotein, a step required for the production of infectious viral particles [6]. Because they have limited bioavailability, they are co-administered with a pharmacologic “booster”, a low and virologically inactive dose of ritonavir a pharmacokinetic enhancer [7]

Methods

Results

Discussion

Conclusion