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Viral Decay Dynamics and Mathematical Modeling of Treatment Response: Evidence of Lower in vivo Fitness of HIV-1 Subtype C

Shet, Anita and Nagaraja, Pradeep and Dixit, Narendra M (2016) Viral Decay Dynamics and Mathematical Modeling of Treatment Response: Evidence of Lower in vivo Fitness of HIV-1 Subtype C. In: JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 73 (3). pp. 245-251.

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Official URL: http://dx.doi.org/10.1097/QAI.0000000000001101

Abstract

Background: Despite the high prevalence of HIV-1 subtype C (HIV-1C) worldwide, information on HIV-1C viral dynamics and response to antiretroviral therapy (ART) is limited. We sought to measure viral load decay dynamics during treatment and estimate the within-host basic reproductive ratio, R-0, and the critical efficacy, epsilon(c), for successful treatment of HIV-1C infection. Methods: Individuals initiated on first-line ART in India and monitored for 6 months of treatment were considered. Viral load, CD4(+) count, and adherence data were collected at baseline, 4, 12, 16 and 24 weeks after ART initiation. Drug resistance genotyping was performed at baseline. R-0 and epsilon(c) were estimated using a mathematical model. Results: Among 257 patients with complete data, mean baseline viral load was 5.7 log(10) copies per milliliter and median CD4(+) count was 165 cells per cubic millimeter. Primary drug resistance was present in 3.1% at baseline. At 6 months, 87.5% had undetectable viral load, indicating excellent response to ART despite high baseline viremia. After excluding those with transmitted resistance, suboptimal adherence and viral rebound, data from 112 patients were analyzed using a mathematical model. We estimated the median R-0 to be 5.3. The corresponding epsilon(c) was similar to 0.8. Conclusions: These estimates of R-0 and epsilon(c) are smaller than current estimates for HIV-1B, suggesting that HIV-1C exhibits lower in vivo fitness compared with HIV-1B, which allows successful treatment despite high baseline viral loads. The lower fitness, and potentially lower virulence, together with high viral loads may underlie the heightened transmission potential of HIV-1C and its growing global spread.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the LIPPINCOTT WILLIAMS & WILKINS, TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
Department/Centre: Division of Mechanical Sciences > Chemical Engineering
Depositing User: Id for Latest eprints
Date Deposited: 07 Jan 2017 09:45
Last Modified: 22 Oct 2018 09:28
URI: http://eprints.iisc.ac.in/id/eprint/55867

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