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Review
. 2017 Dec 28;10(1):10.
doi: 10.3390/v10010010.

Genotypic and Phylogenetic Insights on Prevention of the Spread of HIV-1 and Drug Resistance in "Real-World" Settings

Bluma G Brenner  1 , Ruxandra-Ilinca Ibanescu  2 , Isabelle Hardy  3 , Michel Roger  4
Affiliations
Review

Genotypic and Phylogenetic Insights on Prevention of the Spread of HIV-1 and Drug Resistance in "Real-World" Settings

Bluma G Brenner et al. Viruses. .

Abstract

HIV continues to spread among vulnerable heterosexual (HET), Men-having-Sex with Men (MSM) and intravenous drug user (IDU) populations, influenced by a complex array of biological, behavioral and societal factors. Phylogenetics analyses of large sequence datasets from national drug resistance testing programs reveal the evolutionary interrelationships of viral strains implicated in the dynamic spread of HIV in different regional settings. Viral phylogenetics can be combined with demographic and behavioral information to gain insights on epidemiological processes shaping transmission networks at the population-level. Drug resistance testing programs also reveal emergent mutational pathways leading to resistance to the 23 antiretroviral drugs used in HIV-1 management in low-, middle- and high-income settings. This article describes how genotypic and phylogenetic information from Quebec and elsewhere provide critical information on HIV transmission and resistance, Cumulative findings can be used to optimize public health strategies to tackle the challenges of HIV in "real-world" settings.

Keywords: HIV drug resistance; HIV-1/AIDS; antiretroviral therapy; genotyping; phylogenetics; treatment-as-prevention.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Phylogenetic surveillance of the introduction and spread of non-B subtypes in Quebec [47]. First genotypes of new non-B subtypes (n = 1395) reflects the diversity of the African pandemic. Transmission clusters of 5+ members reveal onward spread among Men having Sex with Men (MSM, blue) and Heterosexual (HET, pink) groups. Large clusters (20+ members) are circled.
Figure 2
Figure 2
Phylogenetic tree of 31 subtype B large cluster (20+ members) transmission networks fueling onward spread of the epidemic among Men having Sex with Men (MSM) (2004–2015).
Figure 3
Figure 3
Signature genotypic features of HIV-1 variants that are implicated in the genetic barrier to development of resistance (orange), fold-resistance (blue) and viral replicative fitness (green). These include mutations implicated in the resistance to the nucleoside reverse transcriptase (RT) inhibitors (NRTIs), including tenofovir (TDF), zidovudine/AZT (ZDV), stavudine (d4T), didanosine (ddI), non-nucleoside RT inhibitors (NNRTIs), protease inhibitors (PIs), and integrase inhibitors (INIs).
Figure 4
Figure 4
Impact of the choice of drugs in combination regimen on the development of drug resistance. The frequency of resistance in individuals failing first-line treatment, is influenced by the level (fold) resistance conferred by acquired mutations, the negative impact of resistance mutations on viral fitness.
Figure 5
Figure 5
Transmitted resistance to various drug classes. Transmitted resistance to NNRTIs is related to viral fitness of viruses harboring K103N, G190A or Y181C point mutations. Transmitted resistance to NRTIs are related to viruses harboring M41L and revertants at codon 215.
See this image and copyright information in PMC

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