Do HIV‐1 non‐B subtypes differentially impact resistance mutations and clinical disease progression in treated populations? Evidence from a systematic review

Bhargava, Madhavi; Cajas, J; Wainberg, Mark A.; Klein, Marina B.; Pai, Nitika Pant

doi:10.7448/ias.17.1.18944

Cited by 38 publications

(26 citation statements)

References 49 publications

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“…At the same time, baseline CD4 + T cell count and HIV-1 DNA level but not the viral subtypes, were predictors for achieving HIV-1 DNA ≤ 2 log 10 copies/10 6 PBMCs, which is in agreement with previous studies [33]. The influence of subtype specific differences on disease progression may play a less prominent role in HIV-DNA levels after ART initiation [38].…”

Section: Discussionsupporting

confidence: 90%

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

et al. 2020

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Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay. Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log 10 copies/10 6 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log 10 copies/10 6 PBMCs) at week 96 were evaluated using a logistic regression model. Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log 10 copies/10 6 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log 10 copies/10 6 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4 + T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log 10 copies/10 6 PBMCs. Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log 10 copies/10 6 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART.

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Section: Discussionsupporting

confidence: 90%

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

et al. 2020

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“…Routine antiretroviral (ARV) drug resistance testing is useful in choosing an optimal treatment regimen and monitoring its efficiency in clinical practice (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). HIV genotyping has been used successfully in research on HIV transmission clusters and HIV transmission dynamics .…”

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confidence: 99%

Long-Range HIV Genotyping Using Viral RNA and Proviral DNA for Analysis of HIV Drug Resistance and HIV Clustering

et al. 2015

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HIV genotyping is a critical tool for antiviral drug resistance testing that has revolutionized HIV care and advanced HIVrelated research. Routine antiretroviral (ARV) drug resistance testing is useful in choosing an optimal treatment regimen and monitoring its efficiency in clinical practice (1-12). HIV genotyping has been used successfully in research on HIV transmission clusters and HIV transmission dynamics (13-35).Initial broadly used ARV regimens included combinations of nucleoside reverse transcriptase (RT) inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). To monitor the emergence of drug resistance mutations associated with NRTIs and NNRTIs, HIV genotyping targeted viral sequences spanning an approximately 1,000-to 1,300-bp region of the HIV-1 genome encoding viral protease and partial RT, using viral RNA as a template for amplification. While the RNA-based approach works well in antiretroviral therapy (ART)-naive individuals, it is less successful if levels of viral replication are low, such as in individuals on ART. The sequence length of traditional RNAbased HIV genotyping for drug resistance is relatively short and does not cover the HIV-1 region encoding viral integrase or the viral envelope, hindering analysis of drug resistance mutations associated with integrase strand transfer inhibitors or entry inhibitors. The global scale up of ARV treatment and successful introduction of integrase strand transfer inhibitors and entry inhibitors into clinical trials and clinical practice necessitate modification of traditional methods of HIV genotyping.Two commercial genotyping assays, ViroSeq HIV-1 from Abbott Molecular and TruGene HIV-1 from Siemens Molecular Diagnostics, have been widely used for analysis of HIV-1-associated drug resistance. Both genotyping kits were extensively tested and validated (36)(37)(38)(39)(40)(41)(42)(43)(44)(45). While the ViroSeq HIV-1 kit is still on the market, Siemens discontinued selling and supporting the TruGene HIV-1 kit in 2014. The ViroSeq HIV-1 kit covers the entire protease-coding region and the RT region encoding the first 320 amino acids. The TruGene HIV-1 sequences span the protease (amino acids 4 to 99)-and RT (amino acids 40 to 240)-coding regions. The CDC supplies WHO-designated and CDC-supported President's Emergency Plan for AIDS Relief (PEPFAR) Genotyping Laboratories with the ATCC HIV-1 Drug Resistance Genotyping kit (46) for drug resistance testing. Many experienced genotyping laboratories have developed their own in-house amplification and sequencing protocols (11,(47)(48)(49)(50)(51)(52)(53)(54)(55)(56), including identification of minor viral variants that are normally missed by commercial genotyping kits (57-61). All of these approaches generally include smaller and more restricted regions for testing HIV-1 drug resistance.Recently, the protocol developed by Gall et al. (62)

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“…Regional epidemics undergo molecular evolution that includes both intrasubtype diversification and recombination, and the emergence of new subtypes and CRFs is well described (Kiwanuka et al, 2008;Tebit and Arts, 2011;Kijak et al, 2013). Molecular surveillance and assessment of HIV-1 diversity is therefore important for vaccine designs (Stephenson and Barouch, 2013), sieve analysis of their clinical trials (Rolland et al, 2011(Rolland et al, , 2012 and potentially for antiviral drug strategies (Bhargava et al, 2014). Moreover, the information obtained from genetic subtypes relates to the study of risk factors and transmission network (Kao et al, 2011;Beyrer et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

An effective tool for identifying HIV-1 subtypes B, C, CRF01_AE, their recombinant forms, and dual infections in Southeast Asia by the multi-region subtype specific PCR (MSSP) assay

Sakkhachornphop

Kijak

Beyrer

et al. 2015

Journal of Virological Methods

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Do HIV‐1 non‐B subtypes differentially impact resistance mutations and clinical disease progression in treated populations? Evidence from a systematic review

Cited by 38 publications

References 49 publications

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

Long-Range HIV Genotyping Using Viral RNA and Proviral DNA for Analysis of HIV Drug Resistance and HIV Clustering

An effective tool for identifying HIV-1 subtypes B, C, CRF01_AE, their recombinant forms, and dual infections in Southeast Asia by the multi-region subtype specific PCR (MSSP) assay

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