Etravirine and Rilpivirine Resistance in HIV-1 Subtype Crf01_Ae-Infected Adults Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens

Bunupuradah, Torsak; Ananworanich, Jintanat; Chetchotisakd, Ploenchan; Kantipong, Pacharee; Jirajariyavej, Supunnee; Sirivichayakul, Sunee; Munsakul, Warangkana; Prasithsirikul, Wisit; Sungkanuparph, Somnuek; Bowonwattanuwong, Chureeratana; Klinbuayaem, Virat; Petoumenos, Kathy; Hirschel, Bernard; Bhakeecheep, Sorakij; Ruxrungtham, Kiat

doi:10.3851/imp1906

Cited by 27 publications

(23 citation statements)

References 28 publications

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“…A study focused on HIV-1 subtype CRF01_AE showed that the presence of mutations associated with resistance to rilpivirine are uncommon in patients infected by this subtype and failing a first-line NNRTI-containing regimen [183]. However, cross-resistance between rilpivirine and etravirine was high.…”

Section: Development Of Resistance To Antiretroviral Therapy Amongmentioning

confidence: 99%

“…However, cross-resistance between rilpivirine and etravirine was high. Moreover, approximately 60% of patients had a high level of etravirine resistance, thus suggesting that the role of etravirine in HIV-1 subtype CRF01_AE infected patients in second-line therapy is limited in late NNRTI failure settings [183]. …”

Section: Development Of Resistance To Antiretroviral Therapy Amongmentioning

confidence: 99%

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HIV-1 Genetic Variability and Clinical Implications

2013

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Despite advances in antiretroviral therapy that have revolutionized HIV disease management, effective control of the HIV infection pandemic remains elusive. Beyond the classic non-B endemic areas, HIV-1 non-B subtype infections are sharply increasing in previous subtype B homogeneous areas such as Europe and North America. As already known, several studies have shown that, among non-B subtypes, subtypes C and D were found to be more aggressive in terms of disease progression. Luckily, the response to antiretrovirals against HIV-1 seems to be similar among different subtypes, but these results are mainly based on small or poorly designed studies. On the other hand, differences in rates of acquisition of resistance among non-B subtypes are already being observed. This different propensity, beyond the type of treatment regimens used, as well as access to viral load testing in non-B endemic areas seems to be due to HIV-1 clade specific peculiarities. Indeed, some non-B subtypes are proved to be more prone to develop resistance compared to B subtype. This phenomenon can be related to the presence of subtype-specific polymorphisms, different codon usage, and/or subtype-specific RNA templates. This review aims to provide a complete picture of HIV-1 genetic diversity and its implications for HIV-1 disease spread, effectiveness of therapies, and drug resistance development.

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Section: Development Of Resistance To Antiretroviral Therapy Amongmentioning

confidence: 99%

Section: Development Of Resistance To Antiretroviral Therapy Amongmentioning

confidence: 99%

HIV-1 Genetic Variability and Clinical Implications

2013

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“…In contrast, Y181C, which commonly occurs with nevirapine but not with efavirenz-containing regimens, confers partial cross-resistance to etravirine. [72] Given the complexity of determining residual activity to etravirine when NNRTI-associated mutations are present, a ‘genotypic susceptibility score’ (GSS) has been developed to predict etravirine susceptibility (figure 3). [58]…”

Section: Drug Resistance By Antiretroviral (Arv) Classesmentioning

confidence: 99%

“…This scenario increases the likelihood that a patient may harbour multiple minority variant NNRTI-resistant virus lineages, including some that may be associated with high-level etravirine resistance. [72,182]…”

Section: Salvage Therapymentioning

confidence: 99%

HIV-1 Antiretroviral Resistance

Tang

Shafer

2012

Drugs

269

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“…However, we failed to demonstrate this association in our study which may be due to 1) different immune responses in children compared to adults and a different HIV-1 clade. The majority of Thais are infected by HIV subtypes CRF01_AE [13]. There is limited data of APOBEC3G genotypes and association to the changes in HIV-RNA in populations infected with different HIV clades.…”

Section: Discussionmentioning

confidence: 99%

Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency

et al. 2012

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IntroductionHuman APOBEC3G is a host defense factor that potently inhibits HIV replication. We hypothesize that HIV-infected children with a genetic variant of APOBEC3G will have a more rapid disease progression.MethodsAntiretroviral therapy (ART)-naïve children, aged 1–12 years old with CD4 15-24% and without severe HIV-related symptoms were enrolled. The children had CD4% and absolute CD4 counts every 12 weeks and HIV-RNA every 24 weeks until 144 weeks. ART was started when CD4% declined to < 15% or AIDS-related events developed.APOBEC3G genetic variants were performed by PCR-based restriction fragment length polymorphism techniques from peripheral blood mononuclear cells. Random-effect linear regression analysis was performed to correlate APOBEC3G genotypes and disease progression.Results147 children, 35% male, with a median (IQR) age of 6.5 (4.3-8.8) years were enrolled. CDC N:A:B were 1:63:36%. Median baseline values were 20% for CD4% 605 cells/mm3 for CD4 count and 4.7 log10copies/mL for HIV-RNA.The frequencies of APOBEC3G genotypes AA (186H/H), AG (186H/R), GG (186R/R) were 86%, 12%, and 2% respectively. The APOBEC3G genotype GG was associated with a significant decline in CD4% -5.1% (−8.9 to −1.2%), p<0.001, and CD4 counts −226 (−415 to −34) cells/mm3, p<0.001 by random-effect liner regression analysis. No significant associations of APOBEC3G genotypes with HIV-RNA changes overtime (p=0.16) or progression to CDC B and C (p=0.49) were observed.ConclusionsAPOBEC3G genotype GG was significantly associated with a more rapid decline in CD4. APOBEC3G’s antiviral effects on HIV disease progression in children should be further explored.

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Etravirine and Rilpivirine Resistance in HIV-1 Subtype Crf01_Ae-Infected Adults Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens

Abstract: Approximately 60% of patients had high-level ETR resistance. The role of ETR in second-line therapy is limited in late NNRTI failure settings. RVP RAMs were uncommon, but cross-resistance between ETR and RVP was high.

Cited by 27 publications

References 28 publications

HIV-1 Genetic Variability and Clinical Implications

HIV-1 Genetic Variability and Clinical Implications

HIV-1 Antiretroviral Resistance

Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency

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