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Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity.

ABSTRACT: Triple-drug therapies have transformed HIV from a fatal condition to a chronic one. These therapies should prevent HIV drug resistance evolution, because one or more drugs suppress any partially resistant viruses. In practice, such therapies drastically reduced, but did not eliminate, resistance evolution. In this article, we reanalyze published data from an evolutionary perspective and demonstrate several intriguing patterns about HIV resistance evolution - resistance evolves (1) even after years on successful therapy, (2) sequentially, often via one mutation at a time and (3) in a partially predictable order. We describe how these observations might emerge under two models of HIV drugs varying in space or time. Despite decades of work in this area, much opportunity remains to create models with realistic parameters for three drugs, and to match model outcomes to resistance rates and genetic patterns from individuals on triple-drug therapy. Further, lessons from HIV may inform other systems.

SUBMITTER: Feder AF

PROVIDER: S-EPMC8412921 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity.

Feder Alison F AF Harper Kristin N KN Brumme Chanson J CJ Pennings Pleuni S PS

eLife 20210902

Triple-drug therapies have transformed HIV from a fatal condition to a chronic one. These therapies should prevent HIV drug resistance evolution, because one or more drugs suppress any partially resistant viruses. In practice, such therapies drastically reduced, but did not eliminate, resistance evolution. In this article, we reanalyze published data from an evolutionary perspective and demonstrate several intriguing patterns about HIV resistance evolution - resistance evolves (1) even after yea ...[more]

PMID: 34473060

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Project description:BackgroundUtilizing population-based survey data in epidemiological research with a spatial perspective can integrate valuable context into the dynamics of HIV prevalence in West Africa. However, the situation in the Mano River Union (MRU) countries is largely unknown. This research aims to perform an ecological study to determine the HIV prevalence patterns in MRU.MethodsWe analyzed Demographic and Health Survey (DHS) and AIDS Indicator Survey (AIS) data on HIV prevalence in MRU from 2005 to 2020. We examined the country-specific, regional-specific and sex-specific ratios of respondents to profile the spatial-temporal heterogeneity of HIV prevalence and determine HIV hot spots. We employed Geodetector to measure the spatial stratified heterogeneity (SSH) of HIV prevalence for adult women and men. We assessed the comprehensive correct knowledge (CCK) about HIV/AIDS and HIV testing uptake by employing the Least Absolute Shrinkage and Selection Operator (LASSO) regression to predict which combinations of CCKs can scale up the ratio of HIV testing uptake with sex-specific needs.ResultsIn our analysis, we leveraged data for 158,408 respondents from 11 surveys in the MRU. From 2005-2015, Cote d'Ivoire was the hot spot for HIV prevalence with a Gi_Bin score of 3, Z-Score 8.0-10.1 and P < 0.001. From 2016 to 2020, Guinea and Sierra Leone were hot spots for HIV prevalence with a Gi_Bin score of 2, Z-Score of 3.17 and P < 0.01. The SSH confirmed the significant differences in HIV prevalence at the national level strata, with a higher level for Cote d'Ivoire compared to other countries in both sexes with q-values of 0.61 and 0.40, respectively. Our LASSO model predicted different combinations of CCKs with sex-specific needs to improve HIV testing uptake.ConclusionsThe spatial distribution of HIV prevalence in the MRU is skewed and the CCK about HIV/AIDS and HIV testing uptake are far below the threshold target set by UNAIDS for ending the epidemic in the sub-region. Geodetector detected statistically significant SSH within and between countries in the MRU. Our LASSO model predicted that different emphases should be implemented when popularizing the CCK about HIV/AIDS for adult women and men.

Dataset Information

Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity.

Publications

Understanding patterns of HIV multi-drug resistance through models of temporal and spatial drug heterogeneity.

Similar Datasets

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