Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2016 Dec 9;16(1):742.
doi: 10.1186/s12879-016-2092-z.

Early antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child

Affiliations
Case Reports

Early antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child

Paolo Palma et al. BMC Infect Dis. .

Abstract

Background: HIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child.

Case presentation: A perinatally HIV-1 infected infant was treated within 7 weeks of age with zidovudine, lamivudine, nevirapine and lopinavir/ritonavir. At antiretroviral treatment (ART) initiation HIV-1 viral load (VL) and CD4 percentage were >500,000 copies/ml and 35%, respectively. Plasma genotypic resistance test showed a wild-type virus. The child reached VL undetectability after 33 weeks of combination antiretroviral therapy (cART) since he maintained a stable VL <40copies/ml. After 116 weeks on ART we were able to perform amplification and sequencing assay on the plasma virus. At this time VL was <40 copies/ml and CD4 percentage was 40%. Again the genotypic resistance test revealed a wild-type virus. The phylogenetic analysis performed on the HIV-1 pol sequences of the mother and the child revealed that sequences clustered with C subtype reference strains and formed a monophyletic cluster distinct from the other C sequences included in the analysis (bootstrap value >90%). Any major evolutionary divergence was detected.

Conclusions: eART limits the viral evolution avoiding the emergence of new viral variants. This result may have important implications in host immune control and may sustain the challenge search of new personalized immunotherapeutic approaches to achieve a prolonged viral remission.

Keywords: Children; Early antiretroviral treatment; HIV; Immunotherapy; Viral evolution.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Maximum likelihood phylogenetic tree constructed on the pol gene sequences of 102 isolates and additional 4 subtype C references. The tree was rooted using the midpoint rooting method. Branch lenghts were estimated with the best fitting nucleotide substitution model (GTR + G + I) according to a hierarchical likelihood ratio test. The bar at the bottom indicating 0.03 nucleotide substitution per site. The astericks (*) along a branch represent bootstrap support >85%. The 4 C sequences belonged to mother to child transmission chain are shown in red and the cluster involving them is in the gray box. The cartoon summarizes the timing of sampling

References

    1. Santoro MM, Perno CF. HIV-1 Genetic Variability and Clinical Implications. ISRN Microbiol. 2013;2013:481314. doi: 10.1155/2013/481314. - DOI - PMC - PubMed
    1. Scarlatti G, Leitner T, Halapi E, Wahlberg J, Jansson M, Wigzell H, et al. Analysis of the HIV-1 envelope V3-loop sequences from ten mother-child pairs. Ann N Y Acad Sci. 1993;693:277–280. doi: 10.1111/j.1749-6632.1993.tb26282.x. - DOI - PubMed
    1. Joseph SB, Swanstrom R, Kashuba AD, Cohen MS. Bottlenecks in HIV-1 transmission: insights from the study of founder viruses. Nat Rev Microbiol. 2015;13(7):414–25. doi: 10.1038/nrmicro3471. - DOI - PMC - PubMed
    1. Josefsson L, von Stockenstrom S, Faria NR, Sinclair E, Bacchetti P, Killian M, et al. The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over tiime. PNAS. 2013;110(51):4987–96. doi: 10.1073/pnas.1308313110. - DOI - PMC - PubMed
    1. Buzon MJ, Sun H, Li C, Shaw A, Seiss K, Ouyang Z, et al. HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat Med. 2014;20(2):139–42. doi: 10.1038/nm.3445. - DOI - PMC - PubMed

Publication types