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. 2013 Jul 15;208(2):271-4.
doi: 10.1093/infdis/jit168. Epub 2013 Apr 18.

Using Ultradeep Pyrosequencing to Study HIV-1 Coreceptor Usage in Primary and Dual Infection

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Free PMC article

Using Ultradeep Pyrosequencing to Study HIV-1 Coreceptor Usage in Primary and Dual Infection

Gabriel A Wagner et al. J Infect Dis. .
Free PMC article

Abstract

HIV-1 dual infection (DI) and CXCR4 (X4) coreceptor usage are associated with accelerated disease progression but frequency and dynamics of coreceptor usage during DI is unknown. Ultradeep sequencing was used to interrogate for DI and infer coreceptor usage in longitudinal blood samples of 102 subjects. At baseline, X4 usage was high (23 subjects harbored X4 variants) and was not associated with infection duration or DI. Coreceptor usage changed over time in 12 of 47 participants, and X4 usage emerged in 4 of 41 monoinfections vs 2 of 5 superinfections (P = .12), suggesting a weak statistical trend toward occurrence of superinfection and acquiring X4 usage.

Keywords: HIV-1 coinfection; HIV-1 dual infection; HIV-1 superinfection; coreceptor tropism; coreceptor usage; genotypic coreceptor usage prediction; genotypic tropism prediction; next-generation sequencing; ultradeep pyrosequencing.

Figures

Figure 1.
Figure 1.
Prevalence of predicted R5 and X4 coreceptor usage. Participants first-sampled within 3 years after EDI harbored mostly R5 usage (light gray bars), but 23 of 102 (22.5%) had detectable X4 variants (dark gray bars). A significant prevalence of X4 usage was detected at all time intervals, even in the first 3 months after infection (18.8%). Abbreviations: EDI, estimated date of infection; R5 usage, viral population demonstrated R5 coreceptor usage; X4 usage, viral population with >1% X4 variants detected at a false positive rate of 5%.
Figure 2.
Figure 2.
HIV-1 superinfection and inferred X4 coreceptor usage over time. In case G59 A, an increase in the proportion of X4 usage (black solid diamonds) coincided with the detection of a superinfecting strain (pie charts), and X4 variants disappeared when this strain was no longer detected. In case L78 B, low-level detection of X4 usage occurred right before detection of the superinfecting strain, and decreased below 1% when the second strain was detected. HIV-1 RNA viral load (gray squares) over time for each participant is superimposed. Abbreviations: EDI, estimated date of infection; HIV-1, human immunodeficiency virus type 1; X4 usage, viral population with >1% X4 variants detected at a false positive rate of 5%.

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