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Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy.

Lee GQ, Dong W, Mo T, Knapp DJ, Brumme CJ, Woods CK, Kanters S, Yip B, Harrigan PR - PLoS ONE (2014)

Bottom Line: We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462).Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR).Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients.

View Article: PubMed Central - PubMed

Affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.

ABSTRACT

Background: HIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using ("R5") to non-CCR5-using ("non-R5") before and after viral suppression in the initially therapy-naïve HOMER cohort from British Columbia, Canada.

Methods: We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462). Virologic suppression was defined as having two consecutive viral loads of <500 copies/mL, which was the sensitivity limit of most viral load assays at the time. Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR).

Results: When virologic suppression was defined as two-consecutive viral loads <500 copies/mL, 34 (9%) of the 397 patients with pre-therapy R5-virus switched to non-R5 at viral load rebound after a median of 19 months (IQR 8-41 months) of undetectable viremia. Duration of viral load suppression was not a predictor of switch, but lower CD4 count during suppression (median 400 versus 250 cells/mL) and an increased prevalence of pre-therapy non-R5 HIV by "deep" sequencing (median 0.2% versus 3.2%) were independently associated with switch (p = 0.03 and p<0.0001, respectively).

Conclusion: R5-to-non-R5 tropism switches in plasma virus after undetectable viremia were relatively rare events especially among patients with higher CD4 counts during virologic suppression. Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients.

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Study flow chart of our primary analysis: Virologic suppression definition: <500 copies/mL; geno2pheno[coreceptor] FPR cutoff 5.75%.
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pone-0099000-g001: Study flow chart of our primary analysis: Virologic suppression definition: <500 copies/mL; geno2pheno[coreceptor] FPR cutoff 5.75%.

Mentions: HOMER is a well-characterized cohort consisting of 1188 treatment-naïve HIV-infected adults in British Columbia who initiated highly active antiretroviral therapy (HAART) between 1996 and 1999 [34]–[36]. As shown in Figure 1, a retrospective search of this database showed a subgroup of 462 individuals satisfied all four inclusion criteria of our primary analysis: individuals who (1) had at least one population-based sequencing tropism test result within six-months before their first exposure to HAART (“baseline tropism”); (2) had at least two consecutive samples collected with viral loads below 500 copies/mL post-HAART initiation (“viral suppression”); (3) after viral suppression had at least two consecutive samples collected with viral loads above 500 copies/mL (“viral rebound”); and (4) had genotypic tropism test results available from within six months after the date of viral rebound (“tropism at viral rebound”). Viral suppression was redefined as <50 copies/mL in part of our secondary analysis (n = 276).


Limited evolution of inferred HIV-1 tropism while viremia is undetectable during standard HAART therapy.

Lee GQ, Dong W, Mo T, Knapp DJ, Brumme CJ, Woods CK, Kanters S, Yip B, Harrigan PR - PLoS ONE (2014)

Study flow chart of our primary analysis: Virologic suppression definition: <500 copies/mL; geno2pheno[coreceptor] FPR cutoff 5.75%.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048224&req=5

pone-0099000-g001: Study flow chart of our primary analysis: Virologic suppression definition: <500 copies/mL; geno2pheno[coreceptor] FPR cutoff 5.75%.
Mentions: HOMER is a well-characterized cohort consisting of 1188 treatment-naïve HIV-infected adults in British Columbia who initiated highly active antiretroviral therapy (HAART) between 1996 and 1999 [34]–[36]. As shown in Figure 1, a retrospective search of this database showed a subgroup of 462 individuals satisfied all four inclusion criteria of our primary analysis: individuals who (1) had at least one population-based sequencing tropism test result within six-months before their first exposure to HAART (“baseline tropism”); (2) had at least two consecutive samples collected with viral loads below 500 copies/mL post-HAART initiation (“viral suppression”); (3) after viral suppression had at least two consecutive samples collected with viral loads above 500 copies/mL (“viral rebound”); and (4) had genotypic tropism test results available from within six months after the date of viral rebound (“tropism at viral rebound”). Viral suppression was redefined as <50 copies/mL in part of our secondary analysis (n = 276).

Bottom Line: We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462).Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR).Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients.

View Article: PubMed Central - PubMed

Affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; University of British Columbia, Vancouver, BC, Canada.

ABSTRACT

Background: HIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using ("R5") to non-CCR5-using ("non-R5") before and after viral suppression in the initially therapy-naïve HOMER cohort from British Columbia, Canada.

Methods: We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462). Virologic suppression was defined as having two consecutive viral loads of <500 copies/mL, which was the sensitivity limit of most viral load assays at the time. Viral tropism was inferred by V3-loop-population-sequencing and geno2pheno[coreceptor] with cutoff at 5.75% false positive rate (FPR).

Results: When virologic suppression was defined as two-consecutive viral loads <500 copies/mL, 34 (9%) of the 397 patients with pre-therapy R5-virus switched to non-R5 at viral load rebound after a median of 19 months (IQR 8-41 months) of undetectable viremia. Duration of viral load suppression was not a predictor of switch, but lower CD4 count during suppression (median 400 versus 250 cells/mL) and an increased prevalence of pre-therapy non-R5 HIV by "deep" sequencing (median 0.2% versus 3.2%) were independently associated with switch (p = 0.03 and p<0.0001, respectively).

Conclusion: R5-to-non-R5 tropism switches in plasma virus after undetectable viremia were relatively rare events especially among patients with higher CD4 counts during virologic suppression. Our study supports the use of pre-suppression tropism results if maraviroc is being considered during virologic suppression in this subgroup of patients.

Show MeSH
Related in: MedlinePlus