Appearance of Drug Resistance-Associated Mutations in Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Derived from Drug-Treated Indonesian Patients

Abstract

Although HIV-1 drug resistance is a major obstacle in Indonesia, information on drug resistance is limited. In this study, the viral subtype and appearance of drug resistance mutations in the HIV-1 protease (PR) and reverse transcriptase (RT) genes were determined among drug-treated, HIV-1-infected patients in Surabaya. HIV-1 patients who received antiretroviral therapy (ART) more than 2 years were randomly recruited regardless of the viral load or ART failure. Fifty-eight HIV-1 PR genes and 53 RT genes were sequenced. CRF01_AE viruses were identified as the predominant strain. Major drug resistance mutations were not detected in the PR genes. In contrast, 37.7% (20/53) of the participants had one or more major drug resistance mutations in the RT genes, predominantly M184V (28.3%), K103N (11.3%), and thymidine analogue mutations (TAMs) (20.8%). The high prevalence of drug resistance mutations in RT genes indicated the necessity of monitoring the effectiveness of ART in Indonesia.

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

“…The existence of distinct subtypes and CRFs reflects the presence of a dy- namic genetic evolutionary process of the virus. The most prominent HIV-1 subtype in Bali found in the present study was CRF01_AE, which is widely prevalent throughout Southeast Asian countries including Indonesia [8,9,17]. Previous HIV-1 genotyping studies in Indonesia reported similar findings.…”

“…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].…”

Appearance of Drug Resistance Mutations Among the Dominant HIV-1 Subtype, CRF01_AE in Maumere, Indonesia

“…ART regimens and the duration of treatments for study participants are shown in Table 2. ART with a combination of 3TC, AZT, and NVP was the major treatment regimen (45.3%), and 56.6% of study participants had been receiving ART for more than 3 years ( These results are consistent with our previous findings [34]; CRF01_AE was the dominant HIV-1 subtype, while the major mutations detected were M184V, K103N, and also TAMs among HIV-1-infected individuals on ART in Surabaya, Indonesia.…”

“…among 46 PR genes (Table 4). Drug resistance-associated minor mutations in PR genes have also been reported in other studies in Indonesia [34]. Minor mutations have been detected in the PR genes of non-B subtypes, including CRF01_AE, as natural polymorphisms [41].…”

“…HIV-1 diversity may also affect the degree of cross-resistance to antiretroviral drugs of the same class, and may ultimately have an impact on clinical outcomes, the preservation of immunological responsiveness, and virologic failure [37,38,39]. The dominant mutations, M184V/I were identified as major drug resistance mutations in patients receiving 3TC and TDF [40,34]. However, in the present study, the M184V mutation was not observed in subtype B or recombinants containing CRF01_AE and subtype B gene fragments.…”