Analysis of pol Integrase Sequences in Diverse HIV Type 1 Strains Using a Prototype Genotyping Assay

Although human immunodeficiency virus type 1 (HIV-1) infection causes serious health problems in Indonesia, information in regard to drug resistance is limited. We performed a genotypic study on HIV-1 integrase derived from drug-naive individuals in Surabaya, Indonesia. Sequencing analysis revealed that no primary mutations associated with drug resistance to integrase inhibitors were detected; however, secondary mutations, V72I, L74I/M, V165I, V201I, I203M, and S230N, were detected in more than 5% of samples. In addition, V201I was conserved among all samples. Most integrase genes were classified into CRF01_AE genes. Interestingly, 40% of the CRF01_AE genes had an unusual insertion in the C-terminus of integrase. These mutations and insertions were considered natural polymorphisms since these mutations coincided with previous reports, and integrase inhibitors have not been used in Indonesia. Our results indicated that further studies may be required to assess the impact of these mutations on integrase inhibitors prior to their introduction into Indonesia.

supporting

confidence: 92%

Detection of Drug Resistance-Associated Mutations in Human Immunodeficiency Virus Type 1 Integrase Derived from Drug-Naive Individuals in Surabaya, Indonesia

Kotaki

Khairunisa

Sukartiningrum

et al. 2014

“…For this analysis, we included data from several recently published studies with large numbers of IN sequences from INI-naïve patients. [11][12][13][14][15] We combined the IN sequences of the 150 patients we describe here with sequences from 4170 previously reported INInaïve patients published in GenBank as of April 15, 2010 to calculate the frequency with which each mutation has been reported at each IN position. Figure 1 shows the proportions of all mutation present in 0.5% of the 4470 INI-naïve patients.…”

Section: Updated Analysis Of Hiv-1 In Polymorphism In Ini-naïve Patientsmentioning

confidence: 99%

HIV-1 Integrase Sequence Variability in Antiretroviral Naïve Patients and in Triple-Class Experienced Patients Subsequently Treated with Raltegravir

Varghese

Liu²,

Rhee³

et al. 2010

Viruses were sequenced from 75 antiretroviral therapy (ARV)-naïve and from 75 ARV-treated patients who subsequently received a raltegravir-containing regimen. No major integrase inhibitor (INI)-resistance mutations were present in the 150 integrase (IN) sequences. Four ARV-naïve (5.3%) and two ARV-treated patients (2.7%) had one of the following minor INI-resistance mutations: L74M, E157Q, G163R, and R263K but there was no association between baseline raltegravir genotype and subsequent response to raltegravir treatment. We also combined our sequences with 4170 previously published group M IN sequences from INI-naïve patients to assess IN sequence variability and compared our findings with those of a study we performed in 2008 using data from 1563 patients. The number of polymorphic IN positions increased from 40% to 41% between the two studies. However, none of the major INI-resistance mutations was found to be polymorphic in either study and there were no significant changes in the prevalence of any of the minor INI-resistance mutations.

“…[11][12][13][14] In addition, such integrase mutations were detected in many subtypes and CRFs of HIV-1 including CRF01_AE viruses. 4,[13][14][15] In these reports, drug resistance-associated mutations were suggested to have appeared due to natural polymorphisms at amino acid positions 72, 74,97,112,119,125,128,138,151,153,154,155,156,157,163,165,201,203,206, and 230 of HIV-1 integrase. 4,[11][12][13][14] According to this information, all secondary mutations detected in this study might be due to natural polymorphism.…”

mentioning

confidence: 99%

“…4,[13][14][15] In these reports, drug resistance-associated mutations were suggested to have appeared due to natural polymorphisms at amino acid positions 72, 74,97,112,119,125,128,138,151,153,154,155,156,157,163,165,201,203,206, and 230 of HIV-1 integrase. 4,[11][12][13][14] According to this information, all secondary mutations detected in this study might be due to natural polymorphism. Nevertheless, we consider that further surveillance studies are necessary to identify drug resistance-associated integrase mutations in HIV-1-infected, drug-naive Thai patients.…”

mentioning

confidence: 99%

Appearance of Drug Resistance-Associated Mutations in Human Immunodeficiency Virus Type 1 CRF01_AE Integrase Derived from Drug-Naive Thai Patients

Isarangkura-na-ayuthaya

Kaewnoo²,

Auwanit³

et al. 2010

CRF01_AE is a major subtype of human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia, including Thailand. We performed genotypic studies on HIV-1 CRF01_AE integrase derived from plasma samples from drug-naive Thai patients. Direct sequencing of amplified CRF01_AE integrase genes revealed that although no primary mutations associated with drug resistance to integrase inhibitors were detected, at least one secondary mutation was found in 96% of samples. Our results indicate that the impact of these mutations on the baseline drug susceptibility of CRF01_AE viruses to integrase inhibitors may need to be addressed prior to the introduction of these drugs in Southeast Asian countries, including Thailand.