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

Abstract

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.

Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

“…The fact that only 0.6% of samples analyzed had INSTIs major RAMs suggests that there will be a lesser likelihood of resistance to INSTIs in Cameroon and that INSTIs will be effective for HIV-infected Cameroonians. Similar trends were observed in other countries in Africa [13,34,[43][44][45], Asia [46][47][48][49][50][51], Europe [52][53][54], and South America [55] where studies showed a low frequency of INSTIs major RAMs.…”

Genotypic characterization of human immunodeficiency virus type 1 isolated in Bali, Indonesia in 2016

“…The mutations, M184V and K103N are commonly detected as multi-drug resistance mutations leading to the virological failure of a first-line NRTIs-and NNRTI-based regimens [16,28]. The appearance pattern of these drug resistance mutations was similar with those in previous studies in Indonesia, Malaysia, Taiwan, Turkey, and USA [17,[18][19][20][21][22][23][24][25][26][27][28][29][30][31]. M184V is a common mutation in treated populations; however, it is very rare among…”

“…Minor mutations have been detected in PR genes of non-B subtypes, including CRF01_AE, as natural polymorphisms [14]. Drug resistance-associated minor mutations in PR genes have also been reported in other studies in Indonesia [11,17,18].…”

“…Other drugs, including didanosine (ddI), etravirine (ETR), and rilpivirine (RPV), are uncommon in the country. Although ART is successful in Indonesia, the emergence of drug resistance has been reported among treatment failure cases as well as ARTnaïve individuals [16][17][18][19].…”

Transmission dynamics of HIV-1 subtype B strains in Indonesia

“…The 5′ terminal half of the HIV-1 genome (former fragment) and 3′ terminal half of the genome (latter fragment) were individually amplified by nested PCR using the Expand Long Template PCR System (Roche Diagnostics). Regarding the former fragment, first-round PCR was performed with the msf12b 24,25 and DRIN02 primers 26 and was followed by second-round nested PCR with the f2nst 24 and DRIN04 primers 26 . The conditions for PCR were as follows: in first PCR, initial denaturation at 94 °C for 2 minutes followed by 10 cycles of 94 °C for 10 seconds, 55 °C for 30 seconds, and 68 °C for 4 minutes, and 25 cycles of 94 °C for 15 seconds, 55 °C for 30 seconds, and 68 °C for 4 minutes and 20 seconds, and final extension at 68 °C for 7 minutes.…”