Surveillance of Genotypic Resistance Mutations in Chronic HIV-1 Treated Individuals After Completion of the National Access to Antiretroviral Program in Thailand

Sukasem, Chonlaphat; Churdboonchart, Vina; Chasombat, Sanchai; Kohreanudom, Surapol; Watitpun, Chotip; Pasomsub, Ekawat; Piroj, Wantanich; Tiensuwan, Montip; Chantratita, Wasun

doi:10.1007/s15010-007-6169-x

Cited by 23 publications

(19 citation statements)

References 15 publications

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“…Second are data to support a potential risk-based, prioritized approach to baseline ARV-DR testing among ARV drug-naïve, recently infected HIV patients who report a sexual partner with ARV non-adherence or GPO-VIR treatment failure. While the temporal rise in ARV-DR was not statistically significant, the trend is consistent with a short list of observational studies from Thailand that have characterized the emergence of ARV-DR among persons with ARV experience and treatment failure despite a universal ARV access programme [11][12]. Together, these surveillance and cohort studies suggest that additional system-, provider-and patient-level support is needed to secure ARV drug delivery and minimize the emergence of ARV-DR.…”

Section: Discussionsupporting

confidence: 79%

“…Together, these surveillance and cohort studies suggest that additional system-, provider-and patient-level support is needed to secure ARV drug delivery and minimize the emergence of ARV-DR. The prior studies in ARV-experienced patients have identified the need for national surveillance for baseline ARV resistance among HIV drug-naïve patients, while generic NNRTI-based regimens (GPO-VIR) remain first-line treatment and recommendations for resistance testing are selective [11][12]. While our data do not support routine ARV-DR testing among all ARV-naïve patients in Thailand, our findings suggest that baseline ARV-DR may be justified in newly diagnosed patients with HIV infection who identify an ARV-experienced, HIV-infected sexual partner who acknowledges ARV non-adherence or treatment failure.…”

Section: Discussionmentioning

confidence: 99%

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Antiretroviral drug resistance among antiretroviral‐naïve persons with recent HIV infection in Thailand

Thatrimontrichai

Jirayasethpong²,

Sa-nguansilp

et al. 2008

HIV Medicine

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ObjectivesTo evaluate the prevalence and patterns of antiretroviral (ARV) drug resistance (ARV-DR) among ARV drug-naïve, recently infected persons with HIV in the 4-year interval (2003)(2004)(2005)(2006) after the inception of the National Access to ARV Programme for People who have AIDS in Thailand. MethodsCross-sectional study of patients with recent HIV infection for HIV risks, ARV-DR risks and baseline ARV-DR. ResultsSeven of the 305 patients (2%) had baseline ARV-DR. Via contract tracing, all seven patients with transmitted ARV-DR identified sexual partners with prior ARV treatment failure and had documented low (o75%) ARV adherence. Annual ARV-DR increased from 0 to 5.2% (P 5 0.06) between 2003 and 2006. ConclusionsReport of sexual partners with potential HIV and ARV drug exposures can prompt baseline ARV-DR testing of at-risk individuals, while behavioural interventions for adherence and safer sex are refined to minimize the emergence of resistance to generic, fixed-dose combination stavudine, lamivudine and nevirapine (GPO-VIR) therapy.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Antiretroviral drug resistance among antiretroviral‐naïve persons with recent HIV infection in Thailand

Thatrimontrichai

Jirayasethpong²,

Sa-nguansilp

et al. 2008

HIV Medicine

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“…Finally, the connection of the Thai HIV-1 epidemic with other epidemics in the region, through travel and trafficking of drugs and persons, has been reflected in the genetic relatedness of Thai strains to those from other countries in the Golden Triangle (i.e., a major illicit opium-producing area spanning Myanmar [Burma], Vietnam, Laos, and Thailand) (34,35) and China (36). Subtypes A, C, D, and CRF02_AG-which are more common in African epidemics-have been detected sporadically (37)(38)(39); however, to date there have been no indications that these strains have spread locally.…”

mentioning

confidence: 99%

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Kijak

Tovanabutra

Rerks-Ngarm

et al. 2013

J Virol

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The RV144 HIV-1 vaccine trial (Thailand, 2003 to 2009), using immunogens genetically matched to the regional epidemic, demonstrated the first evidence of efficacy for an HIV-1 vaccine. Here we studied the molecular evolution of the HIV-1 epidemic from the time of immunogen selection to the execution of the efficacy trial. We studied HIV-1 genetic diversity among 390 volunteers who were deferred from enrollment in RV144 due to preexisting HIV-1 infection using a multiregion hybridization assay, full-genome sequencing, and phylogenetic analyses. The subtype distribution was 91.7% CRF01_AE, 3.5% subtype B, 4.3% B/CRF01_AE recombinants, and 0.5% dual infections. CRF01_AE strains were 31% more diverse than the ones from the 1990s Thai epidemic. Sixty-nine percent of subtype B strains clustered with the cosmopolitan Western B strains. Ninety-three percent of B/CRF01_AE recombinants were unique; recombination breakpoint analysis showed that these strains were highly embedded within the larger network that integrates recombinants from East/Southeast Asia. Compared to Thai sequences from the early 1990s, the distance to the RV144 immunogens increased 52% to 68% for CRF01_AE Env immunogens and 12% to 29% for subtype B immunogens. Forty-three percent to 48% of CRF01_AE sequences differed from the sequence of the vaccine insert in Env variable region 2 positions 169 and 181, which were implicated in vaccine sieve effects in RV144. In conclusion, compared to the molecular picture at the early stages of vaccine development, our results show an overall increase in the genetic complexity of viruses in the Thai epidemic and in the distance to vaccine immunogens, which should be considered at the time of the analysis of the trial results.

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“…This finding might discourage the use of EFdA as a first-line therapy, because it might preclude 3TC and FTC from subsequent use in these patients. However, M184I/V mutations are already prevalent in treatment-experienced patients due to the widespread use of both 3TC and FTC in HAART (20,25). Indeed, despite the appearance of M184V/I-containing variants in the rebounded virus after drug was removed, EFdA successfully controlled virus burden to undetectable levels in both blood and tissues throughout the interval of therapy.…”

Section: Discussionmentioning

confidence: 99%

Response of Simian Immunodeficiency Virus to the Novel Nucleoside Reverse Transcriptase Inhibitor 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine In Vitro and In Vivo

Murphey‐Corb

Rajakumar

Michael

et al. 2012

Antimicrob Agents Chemother

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e Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are essential components in first-line therapy for human immunodeficiency virus (HIV) infection. However, long-term treatment with existing NRTIs can be associated with significant toxic side effects and the emergence of drug-resistant strains. The identification of new NRTIs for the continued management of HIVinfected people therefore is paramount. In this report, we describe the response of a primary isolate of simian immunodeficiency virus (SIV) to 4=-ethynyl-2-fluoro-2=-deoxyadenosine (EFdA) both in vitro and in vivo. EFdA was 3 orders of magnitude better than tenofovir (TFV), zidovudine (AZT), and emtricitabine (FTC) in blocking replication of SIV in monkey peripheral blood mononuclear cells (PBMCs) in vitro, and in a preliminary study using two SIV-infected macaques with advanced AIDS, it was highly effective at treating SIV infection and AIDS symptoms in vivo. Both animals had 3-to 4-log decreases in plasma virus burden within 1 week of EFdA therapy (0.4 mg/kg of body weight, delivered subcutaneously twice a day) that eventually became undetectable. Clinical signs of disease (diarrhea, weight loss, and poor activity) also resolved within the first month of treatment. No detectable clinical or pathological signs of drug toxicity were observed within 6 months of continuous therapy. Virus suppression was sustained until drug treatment was discontinued, at which time virus levels rebounded. Although the rebound virus contained the M184V/I mutation in the viral reverse transcriptase, EFdA was fully effective in maintaining suppression of mutant virus throughout the drug treatment period. These results suggest that expanded studies with EFdA are warranted. N ucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) have proven highly effective in both the treatment of chronic human immunodeficiency virus (HIV) infection (11) and, more recently, as a promising microbicidal prevention strategy for sexually transmitted virus (12). There are seven NRTIs approved for current clinical use, including the nucleoside emtricitabine (FTC) and the nucleotide tenofovir (TFV). Unfortunately, the frequent use of these drugs has resulted in the emergence of resistant virus strains (7,8,10,18). New compounds with potent activity on a wide range of isolates, including NRTI-resistant strains, are critically needed.We and others have previously described a group of 4=-substituted NRTIs that are more potent and have higher selectivity indices in vitro than existing NRTIs (9,13,14,15,16,17). One of the most potent of these compounds, 4=-ethynyl-2-fluoro-2=de-oxyadenosine (EFdA), inhibits HIV-1 replication in primary peripheral blood mononuclear cells (PBMC) with a 50% effective concentration (EC 50 ) of 50 pM, a potency 4 orders of magnitude greater than that of TFV and 400-fold greater than that of AZT (15). It is also nontoxic in vitro at concentrations as high as 10 M, which results in an in vitro selectivity index greater than 200,000. Furthermore, EFdA retains...

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Surveillance of Genotypic Resistance Mutations in Chronic HIV-1 Treated Individuals After Completion of the National Access to Antiretroviral Program in Thailand

Cited by 23 publications

References 15 publications

Antiretroviral drug resistance among antiretroviral‐naïve persons with recent HIV infection in Thailand

Antiretroviral drug resistance among antiretroviral‐naïve persons with recent HIV infection in Thailand

Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Response of Simian Immunodeficiency Virus to the Novel Nucleoside Reverse Transcriptase Inhibitor 4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine In Vitro and In Vivo

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