TY - JOUR
T1 - Viral Decay Dynamics and Mathematical Modeling of Treatment Response
T2 - Evidence of Lower in vivo Fitness of HIV-1 Subtype C
AU - Shet, Anita
AU - Nagaraja, Pradeep
AU - Dixit, Narendra M.
N1 - Funding Information:
Supported byWellcome Trust/DBT India Alliance Senior Fellowships IA/S/13/2/501017 (AS) and IA/S/14/1/501307 (NMD).
Publisher Copyright:
© Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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, ϵ 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 ϵ 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 ϵ c was ∼0.8. Conclusions: These estimates of R 0 and ϵ 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.
AB - 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, ϵ 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 ϵ 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 ϵ c was ∼0.8. Conclusions: These estimates of R 0 and ϵ 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.
KW - HIV-1 subtype C
KW - basic reproductive ratio
KW - first-line ART
KW - in vivo fitness
KW - mathematical modeling
KW - viral dynamics
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U2 - 10.1097/QAI.0000000000001101
DO - 10.1097/QAI.0000000000001101
M3 - Article
C2 - 27273158
AN - SCOPUS:84973315130
VL - 73
SP - 245
EP - 251
JO - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
JF - Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
SN - 1525-4135
IS - 3
ER -