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Early ART Stalls Viral Evolution in Infant But Does Not Stop Replication
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IAS 2015, July 19-22, 2015, Vancouver
Mark Mascolini
Antiretroviral therapy (ART) within 7 weeks of birth virtually halted HIV evolution through 177 weeks in a case study, but low-level viral replication could be detected by week 177 [1].
Researchers from Rome's Tor Vergata University and collaborators noted that the Mississippi baby case showed that HIV eventually rebounds after suspension of successful early ART in infants. Although HIV dynamics experts hope that rapid and sustained ART for infants will limit replication enough to stifle viral diversity, demonstrating that outcome has proved difficult because of challenges in amplifying and sequencing virus during viral suppression.
The Tor Vergata team aimed to address that challenge in a study of an infant treated within weeks of birth. They monitored viral load with an ultrasensitive assay and tested for emergence of resistant virus by genotype. They evaluated genetic evolution of HIV in the pol gene and used a neighbor-joining tree to define the HIV subtype and assess sequence similarities between infant and maternal virus.
This perinatally infected infant began treatment within 7 weeks of birth with zidovudine, lamivudine, nevirapine, and lopinavir/ritonavir. When treatment began the infant's viral load stood above 500,000 copies and the CD4 percent at 35%. Genotyping showed wild-type (nonmutant) virus.
The child reached an undetectable viral load after 33 weeks of treatment and maintained undetectable viremia through 177 weeks of therapy. At that point viremia could be detected but remained below the 40-copy mark. CD4 percent had reached 40%.
Phylogenetic analysis of pol sequences in mother and child established the subtype as C. Comparison of the first and last plasma virus sequences from the infant demonstrated minimal evolutionary distance between the sequences (average 0.000090 +/- 0.000087). Genotyping still showed wild-type virus. But a single nucleotide substitution could be detected at pol position 231 (C to T).
The researchers concluded that early ART for infants limits viral evolution and prevents emergence of new viral variants. They suggested their findings "may have important implications for host immune control and may sustain the challenge of new personalized immunotherapeutic approaches to achieve prolonged viral remission."
Reference
1. Zangari P, Palma P, Tchidjou HK, et al. Early antiretroviral treatment (ART) fails to achieve sustained HIV viral remission but limits viral diversity. IAS 2015. 8th Conference on HIV Pathogenesis, Treatment and Prevention. July 19-22, 2015. Vancouver. Abstract MOPEA025.
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