Human Immunodeficiency Virus Resistance Testing Technologies and Their Applicability in Resource-Limited Settings of Africa

Abdullahi, Idris Nasir; Emeribe, Anthony Uchenna; Ojeamiren, Iduda; Adekola, Hafeez Aderinsayo

doi:10.1177/1178633717749597

“…At the time the samples were collected for this study, 2014–2015, the standard of care for treatment of HIV infection in Botswana was a regimen that included tenofovir, emtricitabine, and efavirenz co-formulated into one pill, Atripla, taken once a day. By using PANDAA, we targeted the most likely mutations to develop to these medications in HIV-1 subtype C, the M184V, K103N and V106M mutations in reverse transcriptase, a targeted and cost-effective approach to genotyping is possible 22 .…”

Section: Discussionmentioning

confidence: 99%

Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naïve HIV-1 Subtype C-infected patients in Botswana

Maruapula¹,

MacLeod²,

Moyo³

et al. 2021

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Background: HIV-1 drug resistance poses a major threat to the success of antiretroviral therapy. The high costs of available HIV drug resistance assays prohibit their routine usage in resource-limited settings. Pan-degenerate amplification and adaptation (PANDAA), a focused genotyping approach based on quantitative PCR (qPCR), promises a fast and cost-effective way to detect HIV drug resistance mutations (HIVDRMs). Given the high cost of current genotyping methods, we sought to use PANDAA for screening key HIVDRMs in antiretroviral-naïve individuals at codons 103, 106 and 184 of the HIV-1 reverse transcriptase gene. Mutations selected at these positions have been shown to be the most common driver mutations in treatment failure. Methods: A total of 103 samples from antiretroviral-naïve individuals previously genotyped by Sanger population sequencing were used to assess and verify the performance of PANDAA. PANDAA samples were run on the ABI 7500 Sequence Detection System to genotype the K103N, V106M and M184V HIVDRMs. In addition, the cost per sample and reaction times were compared. Results: Sanger population sequencing and PANDAA detected K103N mutation in three (2.9%) out of 103 participants. There was no evidence of baseline V106M and M184V mutations observed in our study. To genotype the six HIVDRMs it costs approximately 40 USD using PANDAA, while the reagents cost per test for Sanger population sequencing is approximately 100 USD per sample. PANDAA was performed quicker compared to Sanger sequencing, 2 hours for PANDAA versus 15 hours for Sanger sequencing. Conclusion: The performance of PANDAA and Sanger population sequencing demonstrated complete concordance. PANDAA could improve patient management by providing quick and relatively cheap access to drug-resistance information.

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“…At the time the samples were collected for this study, 2014-2015, the standard of care for treatment of HIV infection in Botswana was a regimen that included tenofovir, emtricitabine, and efavirenz co-formulated into one pill, Atripla, taken once a day. By using PANDAA, we targeted the most likely mutations to develop to these medications in HIV-1 subtype C, the M184V, K103N and V106M mutations in reverse transcriptase, a targeted and cost-effective approach to genotyping is possible 21 .…”

Section: Discussionmentioning

confidence: 99%

Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naïve HIV-1 Subtype C-infected patients in Botswana

Maruapula¹,

MacLeod²,

Moyo³

et al. 2020

View full text Add to dashboard Cite

Background: HIV-1 drug resistance poses a major threat to the success of antiretroviral therapy. The high costs of available HIV drug resistance assays prohibit their routine usage in resource-limited settings. Pan-degenerate amplification and adaptation (PANDAA), a focused genotyping approach based on quantitative PCR (qPCR), promises a fast and cost-effective way to detect HIV drug resistance mutations (HIVDRMs). Given the high cost of current genotyping methods, we sought to use PANDAA for screening key HIVDRMs in antiretroviral-naïve individuals at codons 103, 106 and 184 of the HIV-1 reverse transcriptase gene. Mutations selected at these positions have been shown to be the most common driver mutations in treatment failure. Methods: A total of 103 samples from antiretroviral-naïve individuals previously genotyped by Sanger population sequencing were used to assess and verify the performance of PANDAA. PANDAA samples were run on the ABI 7500 Sequence Detection System to genotype the K103N, V106M and M184V HIVDRMs. In addition, the cost per sample and reaction times were compared. Results: Sanger population sequencing and PANDAA detected K103N mutation in three (2.9%) out of 103 participants. There was no evidence of baseline V106M and M184V mutations observed in our study. To genotype the six HIVDRMs it costs approximately 40 USD using PANDAA, while the reagents cost per test for Sanger population sequencing is approximately 100 USD per sample. PANDAA was performed quicker compared to Sanger sequencing, 2 hours for PANDAA versus 15 hours for Sanger sequencing. Conclusion: The performance of PANDAA and Sanger population sequencing demonstrated complete concordance. PANDAA could improve patient management by providing quick and relatively cheap access to drug-resistance information.

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“…Although combination antiretroviral therapy (cART) is widely used in AIDS patients, it is limited by the expensive cost, side effects, viral mutation or drug resistance ( McArthur et al, 2003 ; Nasir et al, 2017 ). HIV-1 entry/fusion inhibitors have the potential to block the earliest step of viral infection and intercept the virus before it invades target cells ( Xu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

3-Hydroxyphthalic Anhydride- Modified Rabbit Anti-PAP IgG as a Potential Bifunctional HIV-1 Entry Inhibitor

Zhang

¹

,

Chen

²

,

Yu

³

et al. 2018

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Several studies have reported that amyloid fibrils in human semen formed from a naturally occurring peptide fragment of prostatic acidic phosphatase (PAP248-286), known as semen-derived enhancer of viral infection (SEVI), could dramatically enhance human immunodeficiency virus type 1 (HIV-1) infection. Accordingly, SEVI might serve as a novel target for new antiviral drugs or microbicide candidates for the prevention of sexually transmitted HIV. Theoretically, a special anti-PAP or anti-SEVI antibody could reduce the enhancement of viral infection by blocking the binding of HIV and SEVI fibrils. Here, 3-hydroxyphthalic anhydride modified anti-PAP248-286 antibody, named HP-API, exhibited broad-spectrum and highly effective anti-HIV-1 activities on different subtypes and tropism. By using time-of-addition, cell–cell fusion and a single-cycle HIV-1 infection assays, we demonstrated that HP-API is an HIV-1 entry/fusion inhibitor. Mechanism studies suggest that HP-API inhibited HIV-1 entry/fusion by targeting both HIV-1 gp120 envelop and CD4 receptor on the host cell specifically. It is noteworthy that HP-API abrogated the formation of SEVI fibrils and partially interfered with SEVI-mediated enhancement of HIV-1 infection. Based on these findings, HP-API could be considered a bifunctional HIV-1 entry/fusion inhibitor with high potential.

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Human Immunodeficiency Virus Resistance Testing Technologies and Their Applicability in Resource-Limited Settings of Africa

Cited by 8 publications

References 37 publications

Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naïve HIV-1 Subtype C-infected patients in Botswana

Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naïve HIV-1 Subtype C-infected patients in Botswana

Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naïve HIV-1 Subtype C-infected patients in Botswana

3-Hydroxyphthalic Anhydride- Modified Rabbit Anti-PAP IgG as a Potential Bifunctional HIV-1 Entry Inhibitor

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