India-US clinical study on HIV type 1 protease suggest darunavir as choice of third-line regimen

An India –US clinical study has revealed that majority of human immunodeficiency virus (HIV) type 1 protease (PR) patients receiving second-line anti retroviral therapy have begun to show drug resistance.
PR, essential for the viral replication and the mutation profiles, suggest that darunavir might be the drug of choice for third-line regimens in India for HIV, according to the study carried out by the India and US researchers.
The team represents YRG Centre for AIDS Research and Education, Chennai, Department of Medicine, Brown University, Providence, Rhode Island, and Division of Infectious Diseases, Stanford University, California.
PR inhibitors (PIs) like indinavir (IDV), ritonavir (RTV), saquinavir (SQV), nelfinavir (NFV), fosamprenavir (FPV), lopinavir (LPV), atazanavir (ATV), and darunavir (DRV) have been approved by the US FDA and commercially available. In India, these drugs are often used as second-line treatment for those where first-line treatment failed, they reported.
A clinical study was carried out on 107 patients at the YRG Centre in Chennai receiving second-line antiretroviral treatment which was conducted to report on types of drug resistance mutations among those with detectable HIV type 1 plasma viral loads (PVLs). The PVLs were measured using Abbott m2000rt real-time polymerase chain reaction. The genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8.
Of 45 patient plasma specimens consecutively analysed, 30 cases had undetectable PVLs and 77 cases of the 107 patients had a median PVL. Sequencing was done for 45 samples with PVLs. Based on the mutational profiles observed, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47 per cent showed resistance to lopinavir, 58 per cent showed resistance to atazanavir, and 60 per cent showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir.
According to Prof. Suniti Solomon, director, YRG CARE, although India has seen increased access to second-line anti retroviral since January 2009, there are few studies on PR drug resistance to these drugs from this region.
YRG CARE, is a tertiary HIV referral centre for southern India which has provided a continuum of care for 12,000 individuals infected with HIV. All patients are treated according to World Health Organization (WHO) treatment guidelines and are advised to initiate highly active ART before CD4 cell counts drop to 200 cells with an AIDS-defining illness.
This study which is also published early this month in the Clinical Infectious Diseases Advance Access Journal aimed to characterize the pattern of PR resistance mutations among southern Indian patients who have been exposed to PI-based, second-line therapy.
At present, with few third-line antiretroviral options for subsequent therapy in India, DRV might be the choice for third-line regimens. In contrast, it is important to strengthen the development of technologies for affordable PVL monitoring for early detection of virologic failure and genotype-guided switching regimens could improve treatment outcomes, according to the research report.
Source:Pharmabiz