Prediction of drug-resistance in HIV-1 subtype C based on protease sequences from ART naive and first-line treatment failures in North India using genotypic and docking analysis

Introduction: This study aimed to evaluate the prevalence of resistance mutations in the protease gene of HIV-1 strains isolated from north Indian antiretroviral (ARV) treatment-naive patients and to assess the phylogenetic relatedness of these strains with known HIV-1 strains. Methodology: Fifty-four HIV-1 strains isolated from treatment-naive patients (n = 54) were included in this study. Resistance genotyping for the protease gene was performed using semi-nested PCR and DNA sequencing. The sequences were aligned (ClustalW) and a phylogenetic tree was built (MEGA 4 software). Drug resistance (DR) pattern was analyzed using the Stanford HIV-DR database and the IAS-USA mutation list. For subtyping purposes, all the nucleotide sequences were submitted to the REGA HIV-1 subtyping tool version 2.0l. Results: All the strains (100%) were found to belong to the C subtype and to harbor at least two secondary mutations in the protease gene. The most frequent mutations were H69K and I93L (52 of 52 strains), followed by I15V (80

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“…The presence of K14R mutant may slightly increase resistance to darunavir (DRV) [27]. T74S mutation alone may reduce NFV susceptibility [28].…”

Section: Discussionmentioning

confidence: 99%

Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India

Azam

Malik

Rizvi

et al. 2014

J Infect Dev Ctries

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“…The predominant HIV strain in India is group M subtype C (Seth, ). Although small molecule inhibitor therapies have been successfully used, they are geared for subtype B, and mutations leading to drug resistance have required development of new line of molecules (Toor et al , ). Within India HIV‐1/2 infections have been adequately addressed, through the mandated notification of all reactive results to NACO, and donor referral to Integrated Counseling and Testing Center.…”

Section: Efforts To Limit Tti Through Blood Screening In Indiamentioning

confidence: 99%

Transfusion transmitted infections in thalassaemics: need for reappraisal of blood screening strategy in India

Shyamala

2014

Transfusion Medicine

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The aim of the study was to assess the blood safety in India through prevalence in thalassaemic population. Safety of the blood supply is a subject of great concern for all recipients. This review attempts to assess the relevance and format of tests for viruses in the context of transfusion transmitted infection (TTI) prevalence in India. Serological marker testing for human immunodeficiency virus-1/2 (HIV-1/2), hepatitis C virus (HCV) and hepatitis B virus (HBV) is mandatory in India. Numerous TTI incidents in the repeat recipients supported by results from nucleic acid technology (NAT) testing indicate the deficiencies in blood safety. The β-thalassaemic population (3-17%) in India has been used to reflect on blood safety. The prevalence of HIV-1/2, HCV and HBV in the Indian donor population, the limitations in accessing safe donors, quality of serological tests and the impact on repeat recipients is evaluated. The reports point to prevalence of ˜2% of viral diseases in the blood donor population, and the insufficiency of serology testing resulting in up to 45% TTIs in thalassaemics. The revelation by individual donation (ID) NAT testing, of 1 per 310 units being serology negative-NAT reactive is alarming. Extrapolating the serology negative NAT reactive yields, for an annual blood supply of 7.9 million units, 23,700 units or nearly 100,000 blood components are likely to be infectious. Though the cost for ID-NAT testing is considered unaffordable for a medium development country such as India, the enormity of TTIs will place an unmanageable cost burden on the society.

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“…HIV antiretroviral resistance is a global problem, and the World Health Organization recommends surveillance for the emergence of HIV resistance as a component of all antiretroviral treatment programs [DiazGranados et al, ]. Individuals infected with HIV acquire antiretroviral resistance in one of two ways: (1) transmitted drug resistance (TDR) occurs when antiretroviral‐naïve individuals are infected with viruses already harboring resistance mutations, and (2) acquired drug resistance (ADR) emerges from the selective pressure of antiretrovirals in individuals without fully suppressed viral loads either because of poor adherence or the use of a non‐suppressive regimen [Toor et al, ]. Infected patients with either TDR or ADR are at increased risk for treatment failure.…”

Section: Introductionmentioning

confidence: 99%

Antiretroviral drug resistance among antiretroviral‐naïve and treatment experienced patients infected with HIV in Iran

Baesi

Ravanshad

Ghanbari

et al. 2014

Journal of Medical Virology

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Resistance to antiretroviral therapy (ART) threatens the success of programs to reduce HIV morbidity and mortality, particularly in countries with few treatment options. In the present study, genotype and phenotype data from ART-naïve and experienced hospitalized patients infected with HIV in Tehran, Iran were used to assess the prevalence and types of transmitted (TDR) and acquired drug resistance (ADR) mutations. All 30 participants naïve to ART and 62 of 70 (88.6%) participants receiving ART had detectable viral loads. Among participants receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two (3.2%) of these participants had resistance to one, two, and three drug classes, respectively. High-level resistance to efavirenz (EFV) was more common among participants on EFV-based regimens than high-level lopinavir/ritonivar (LPV/r) resistance among those on LPV/r-based regimens (55.3% vs. 6.7%, P < 0.0001). Two (6.7%) antiretroviral-naïve participants had K103N mutations. These findings document an alarmingly high frequency of multiple HIV drug class resistance in Iran, confirm the presence of TDR, and highlight the need for systematic viral load monitoring and drug resistance testing, including at diagnosis. Expanded access to new antiretroviral medications from additional drug classes is needed.

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Prediction of drug-resistance in HIV-1 subtype C based on protease sequences from ART naive and first-line treatment failures in North India using genotypic and docking analysis

Cited by 20 publications

References 23 publications

Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India

Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India

Transfusion transmitted infections in thalassaemics: need for reappraisal of blood screening strategy in India

Antiretroviral drug resistance among antiretroviral‐naïve and treatment experienced patients infected with HIV in Iran

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