1. The largest HIV-1-infected T cell clones in children on long-term combination antiretroviral therapy contain solo LTRs.
- Author
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Botha JC, Demirov D, Gordijn C, Katusiime MG, Bale MJ, Wu X, Wells D, Hughes SH, Cotton MF, Mellors JW, Kearney MF, and van Zyl GU
- Subjects
- Animals, Antiretroviral Therapy, Highly Active, Proviruses genetics, CD4-Positive T-Lymphocytes, Clone Cells, HIV Long Terminal Repeat, HIV Infections drug therapy, HIV-1 genetics, HIV Seropositivity
- Abstract
Combination antiretroviral therapy (cART) suppresses viral replication but does not cure HIV infection because a reservoir of infectious (intact) HIV proviruses persists in long-lived CD4+T cells. However, a large majority (>95%) of HIV-infected cells that persist on effective cART carry defective (non-infectious) proviruses. Defective proviruses consisting of only a single LTR (solo long terminal repeat) are commonly found as endogenous retroviruses in many animal species, but the frequency of solo-LTR HIV proviruses has not been well defined. Here we show that, in five pediatric donors whose viremia was suppressed on cART for at least 5 years, the proviruses in the nine largest clones of HIV-infected cells were solo LTRs. The sizes of five of these clones were assayed longitudinally by integration site-specific quantitative PCR. Minor waxing and waning of the clones was observed, suggesting that these clones are generally stable over time. Our findings show that solo LTRs comprise a large fraction of the proviruses in infected cell clones that persist in children on long-term cART. IMPORTANCE This work highlights that severely deleted HIV-1 proviruses comprise a significant proportion of the proviral landscape and are often overlooked., Competing Interests: John W. Mellors reports additional research grant funding from USAID and Gilead Sciences, Inc., to the University of Pittsburgh; scientific advisory board member to Gilead Sciences, Inc.; shareholder in Abound Bio, Inc., and MingMed; and share option holder in Infectious Disease Connect.
- Published
- 2023
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