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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Viral load and CD4+ T-cell dynamics in primary HIV-1 subtype C infection
Vladimir Novitsky1, Elias Woldegabriel, Lemme Kebaabetswe
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Insights
Early HIV-1 subtype C infection shows distinct viral RNA evolution patterns. This study characterizes viral load, CD4+ T-cell counts, and proviral DNA kinetics in the first year postseroconversion.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Limited data exists on early Human Immunodeficiency Virus type 1 (HIV-1) subtype C infection kinetics.
- Most prior research focused on HIV-1 subtype B, leaving a knowledge gap for subtype C.
Purpose of the Study:
- To characterize viral RNA, proviral DNA, and CD4+ T-cell dynamics in the initial year of HIV-1 subtype C infection.
- To identify distinct patterns of viral evolution in early subtype C infections.
Main Methods:
- Longitudinal study of 8 acute and 62 recent HIV-1 subtype C infections.
- Quantification of viral RNA, proviral DNA, and CD4+ T-cell counts (including CCR5/CXCR4 expression).
- Analysis of viral and immunological parameters over the first year postseroconversion.
Main Results:
- Viral RNA peaked at 6.25 ± 0.92 log10 copies/mL; distinct patterns of viral load and CD4+ T-cell count changes were observed postseroconversion.
- Proviral DNA showed no clear peak, with a mean of 2.59 ± 0.69 log10 per 10^6 PBMCs.
- In recent infections, viral RNA set point (4.00 ± 0.97 log10) correlated inversely with CD4+ T-cells and directly with proviral DNA.
Conclusions:
- Distinct patterns of viral RNA evolution emerge early in HIV-1 subtype C infection.
- This research enhances understanding of the early pathogenesis of HIV-1 subtype C.
Background:
Most knowledge of primary HIV-1 infection is based on subtype B studies, whereas the evolution of viral parameters in the early phase of HIV-1 subtype C infection is not well characterized.
Methods:
The kinetics of viral RNA, proviral DNA, CD4+ T-cell count, and subsets of CD4+ T cells expressing CCR5 or CXCR4 were characterized in 8 acute and 62 recent subtype C infections over the first year postseroconversion.
Results:
The viral RNA peak was 6.25 +/- 0.92 log10 copies per milliliter. After seroconversion, heterogeneity among acute cases was evident by patterns of change in viral load and CD4+ T-cell count over time. The patterns were supported by the rate of viral RNA decline from peak (P = 0.022), viral RNA means (P = 0.005), CD4 levels (P < 0.001), and CD4 decline to 350 (P = 0.011) or 200 (P = 0.046). Proviral DNA had no apparent peak and its mean was 2.59 +/- 0.69 log10 per 106 peripheral blood mononuclear cell. In recent infections, viral RNA set point was 4.00 +/- 0.97 log10 and viral RNA correlated inversely with CD4+ T cells (P < 0.001) and directly with proviral DNA (P < 0.001).
Conclusions:
Distinct patterns of viral RNA evolution may exist shortly after seroconversion in HIV-1 subtype C infection. The study provides better understanding of the early phase of subtype C infection.
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