Appearance of drug resistance-associated mutations in human immunodeficiency virus type 1 protease and reverse transcriptase derived from drug-treated Indonesian patients.

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.

HIV-1 transmitted drug resistance mutations among antiretroviral therapy-Naïve individuals in Surabaya, Indonesia.

BACKGROUND: The emergence of transmitted drug resistance (TDR) compromises the effect of antiretroviral therapy (ART), resulting in treatment failure of human immunodeficiency virus (HIV) disease. Although more than a decade has passed since ART was introduced into Indonesia, information on TDR is limited. Here, a genotypic study of TDR among ART-naïve individuals was conducted in Surabaya, Indonesia. METHOD: HIV-1 seropositive participants were recruited from the communities of commercial sex workers and intravenous drug users as well as from the university teaching hospital in Surabaya. Protease (PR) and reverse transcriptase (RT) genes were sequenced in order to conduct HIV-1 subtyping and phylogenetic analysis and to detect TDR. TDR was defined as the presence of at least one surveillance drug resistance mutation on the WHO list or major drug resistance mutations in the International AIDS Society-USA panel. RESULT: Fifty two and 47 of the PR and RT genes, respectively, were successfully sequenced in the 58 samples. HIV-1 subtyping revealed that 86.3% (50/58) of the sequenced samples were classified as CRF01_AE, 8.6% as subtype B, 3.4% as B/CRF01_AE, and 1.7% as A/G/CRF01_AE. TDR of PR inhibitors was not detected in this study. In contrast, TDR of RT inhibitors was detected in 4.3% (2/47) of samples. In addition, minor drug resistance mutations were detected in 98.1% (51/52) and 12.8% (6/47) of PR and RT genes, respectively. CONCLUSION: This study clarified the predominance of the CRF01_AE strain in Surabaya, Indonesia. The prevalence of TDR was below 5%, indicating that the currently available first-line regimen is still effective in Surabaya. However, the prevalence might be underestimated since we detected only major population of HIV-1 in individuals. Therefore, continuous surveillance is required in order to detect the emergence of TDR in the early phase.

Detection of drug resistance-associated mutations in human immunodeficiency virus type 1 integrase derived from drug-naive individuals in Surabaya, Indonesia.

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.

High prevalence of HIV-1 CRF01_AE viruses among female commercial sex workers residing in Surabaya, Indonesia.

BACKGROUND: Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) cause serious health problems and have an impact on the Indonesian economy. In addition, the rapid epidemic growth of HIV is continuing in Indonesia. Commercial sex plays a significant role in the spread of HIV; therefore, in order to reveal the current HIV prevalence rate among commercial sex workers (CSWs), we conducted an epidemiological study on HIV infection among CSWs residing in Surabaya, the capital of East Java province of Indonesia with large communities of CSWs. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence of HIV infection among 200 CSWs was studied. In addition, the subtype of HIV type 1 (HIV-1) and the prevalence of other blood-borne viruses, hepatitis B virus (HBV), hepatitis C virus (HCV) and GB virus C (GBV-C), were studied. The prevalence rates of HIV, hepatitis B core antibody, hepatitis B surface antigen, anti-HCV antibodies and anti-GBV-C antibodies were 11%, 64%, 4%, 0.5% and 0% among CSWs involved in this study, respectively. HIV-1 CRF01_AE viral gene fragments were detected in most HIV-positive samples. In addition, most CSWs showed low awareness of sexually transmitted diseases and had unprotected sex with their clients. CONCLUSIONS/SIGNIFICANCE: The HIV prevalence rate among CSWs was significantly higher than that among the general population in Indonesia (0.2-0.4%). In addition, CSWs were at a high risk of exposure to HBV, although chronic HBV infection was less frequently established. Our results suggest the necessity of efficient prevention programs for HIV and other blood-borne viral infections among CSWs in Surabaya, Indonesia.