Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria

Udeze, A. O.; Olaleye, David O.; Odaibo, Georgina N.

doi:10.1371/journal.pone.0231031

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…NRTI resistance was also common, led by the M184V mutation. The predominance of these two mutations is consistent with several previous reports in Nigeria [11,14,15], whereas other studies noted a stronger predominance of Y181C [13,16,18]. Although the prevalence of NNRTI DRMs in our sample supports the move to dolutegravir-based combinations as first-line ART in Nigeria, resistance to NRTIs may still threaten initial treatment regimens.…”

Section: Discussionsupporting

confidence: 91%

“…Protease inhibitor usage was uncommon in NAIIS, which may suggest a weak selective pressure for protease inhibitor resistance. Earlier studies report varying levels of protease inhibitor resistance in Nigeria, possibly because of significant heterogeneity in sample sizes and ART experience [14,17,18]. Two recent studies by Crowell et al [11,15] did not detect any protease inhibitor-associated DRMs.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load

Aliyu

Lawton

Mitchell

et al. 2022

Aids

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c , on behalf on the NAIIS Study Group Background: HIV drug resistance (HIVDR) surveillance is an important tool to monitor threats to progress towards epidemic control. The characterization of HIVDR in Nigeria at the national level is needed to inform both clinical decisions and population-level HIV policy strategies. This study uses data obtained from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) to describe the prevalence and distribution of HIVDR in Nigeria.Methods: NAIIS was a cross-sectional, population-based survey of households throughout Nigeria in 2018. NAIIS was designed to provide estimates of HIV prevalence and related health indicators from a nationally representative sample. The study population included participants aged 15-64 years who tested positive for HIV, had a viral load at least 1000 copies/ml, and had available HIV drug resistance genotypes. HIV isolates were genotyped to detect drug resistance mutations. Individual characteristics of study participants associated with HIVDR were identified using a weighted multivariable logistic regression model.Results: Of 1355 respondents with available HIV genotypes, 293 (19%) had evidence of drug-resistant mutations (DRMs) that conferred resistance to at least one antiretroviral drug. The majority of DRMs observed conferred resistance to NNRTIs (17.6%) and NRTIs (11.2%). HIVDR was associated with being ART-experienced, longer duration on ART, and lower CD4 þ count but not sociodemographic characteristics. Conclusion:The population level DRM prevalence in Nigeria was consistent with what would be expected in a mature HIV treatment landscape. The continued roll out of a

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load

Aliyu

Lawton

Mitchell

et al. 2022

Aids

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“…One intriguing finding was that our analysis showed that CRF02_AG infection was associated with an increased likelihood of L10V and G16E mutations. A study by Udeze et al also showed a higher frequency of these ARTRMs among PLHIV infected with CRF02_AG compared to other HIV variants 55 . Similarly, the risk of the occurrence of RT mutation, S162A, was found to be increased by the administration of NVP and with CRF02_AG infection.…”

Section: Discussionmentioning

confidence: 89%

Antiretroviral therapy resistance mutations among HIV infected people in Kazakhstan

Mukhatayeva

Mustafa

Dzissyuk

et al. 2022

Sci Rep

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In Kazakhstan, the number of people living with HIV (PLHIV) has increased steadily by 39% since 2010. Development of antiretroviral therapy (ART) resistance mutations (ARTRM) is a major hurdle in achieving effective treatment and prevention against HIV. Using HIV pol sequences from 602 PLHIV from Kazakhstan, we analyzed ARTRMs for their association with factors that may promote development of ARTRMs. 56% PLHIV were infected with HIV subtype A6 and 42% with CRF02_AG. The ARTRM Q174K was associated with increased viral load and decreased CD4+ cell count, while infection with CRF02_AG was associated with a lower likelihood of Q174K. Interestingly, CRF02_AG was positively associated with the ARTRM L10V that, in turn, was observed frequently with darunavir administration. Infection with CRF02_AG was positively associated with the ARTRM S162A that, in turn, was frequently observed with the administration of nevirapine, also associated with lower CD4 counts. Zidovudine or Nevirapine receipt was associated with the development of the ARTRM E138A, that, in turn, was associated with lower CD4 counts. Determination of a patient’s HIV variant can help guide ART choice in Kazakhstan. For example, PLHIV infected with CRF02_AG will benefit less from darunavir and nevirapine, and emtricitabine should replace zidovudine.

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“…Since the emergence of acquired immunodeficiency syndrome in 1981, human immunodeficiency virus (HIV) infections have remained a prevalent and persisting global epidemic. There are still many challenges in the treatment of HIV due to high mutation rates [1], conformational heterogeneity, polymorphisms [2], altered glycosylation patterns [3,4], and subsequent glycan shielding [5][6][7]. Current therapies include antiretroviral treatment (ART): a noncurative, life-long treatment that suppresses viral replication [8,9].…”

Section: Introductionmentioning

confidence: 99%

Engineering strategies of Anti-HIV antibody therapeutics in clinical development

Pihlstrom

Bournazos

2023

Current Opinion in HIV and AIDS

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Purpose of reviewAnti-human immunodeficiency virus (HIV) antibody-based therapeutics offer an alternative treatment option to current antiretroviral drugs. This review aims to provide an overview of the Fc- and Fab-engineering strategies that have been developed to optimize broadly neutralizing antibodies and discuss recent findings from preclinical and clinical studies.Recent findingsMultispecific antibodies, including bispecific and trispecific antibodies, DART molecules, and BiTEs, as well as Fc-optimized antibodies, have emerged as promising therapeutic candidates for the treatment of HIV. These engineered antibodies engage multiple epitopes on the HIV envelope protein and human receptors, resulting in increased potency and breadth of activity. Additionally, Fc-enhanced antibodies have demonstrated extended half-life and improved effector function.SummaryThe development of Fc and Fab-engineered antibodies for the treatment of HIV continues to show promising progress. These novel therapies have the potential to overcome the limitations of current antiretroviral pharmacologic agents by more effectively suppressing viral load and targeting latent reservoirs in individuals living with HIV. Further studies are needed to fully understand the safety and efficacy of these therapies, but the growing body of evidence supports their potential as a new class of therapeutics for the treatment of HIV.

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Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria

Cited by 7 publications

References 32 publications

Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load

Prevalence of HIV drug resistance in Nigeria: results from a cross-sectional, population-based survey of Nigerian adults with unsuppressed viral load

Antiretroviral therapy resistance mutations among HIV infected people in Kazakhstan

Engineering strategies of Anti-HIV antibody therapeutics in clinical development

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