Adapting the geno2pheno[coreceptor] tool to HIV-1 subtype CRF01_AE by phenotypic validation using clinical isolates from South-East Asia

Marty, Nina; Saeng-Aroon, Siriphan; Heger, Eva; Thielen, Alexander; Obermeier, Martin; Pfeifer, Nico; Kaiser, Rolf; Klimkait, Thomas

doi:10.1016/j.jcv.2021.104755

Cited by 1 publication

(1 citation statement)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, a recent study showed that in general, the G2P tropism determination might be challenging only for D and CRF01_AE non-B subtype where FPR cut-off adjustments are needed to avoid an excess of X4 predictions. 37 In our population, <1% of individuals were infected by these subtypes; thus, this issue does not affect our reliability of tropism determination.…”

Section: Discussionmentioning

confidence: 84%

Genotypic HIV-1 tropism determination might help to identify people with exhausted treatment options and advanced disease

Bouba

Armenia

Forbici

et al. 2021

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Objectives To evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options. Methods HIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm. Results Overall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count <200 cells/mm3, who were perinatally infected and with a long treatment history significantly increased as FPR levels decreased. Regarding resistance, 933 (67.5%) individuals accumulated at least one class resistance, with 52.7%, 48.2%, 23.5% and 13.2% of individuals showing resistance to NRTIs, NNRTIs, PIs and INIs; while 23.2%, 27.2%, 14.3% and 2.8% harboured resistance to 1, 2, 3 and 4 classes, respectively. Individuals with FPR ≤5% showed a significantly higher level of resistance to PIs, NRTIs and INIs compared with others. The proportion of individuals harbouring strains susceptible to ≤2 active drugs was only about 2%; nonetheless, this proportion doubled (4.6%) in patients infected with FPR ≤5%. Conclusions Our findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.

show abstract

Section: Discussionmentioning

confidence: 84%