Early establishment of a pool of latently infected, resting CD4 ⁺ T cells during primary HIV-1 infection

TLDR

Latently infected, resting CD4⁺ T cells carrying replication‑competent HIV‑1 are found in both untreated and HAART‑treated chronically infected individuals, but it is unclear whether early HAART can block their establishment after primary infection. Initiating HAART as early as 10 days after symptom onset does not prevent the generation of latently infected resting CD4⁺ T cells carrying integrated HIV‑1 DNA or infectious virus, and neither the duration nor timing of therapy correlates with reservoir frequency, underscoring the rapid establishment of latent reservoirs during primary infection.

Abstract

The presence of latently infected, resting CD4 + T cells carrying replication-competent HIV-1 has been demonstrated in chronically infected individuals who are antiretroviral therapy naive as well as in those who are receiving highly active antiretroviral therapy (HAART). It is not clear, however, whether the establishment of a pool of latently infected CD4 + T cells can be blocked by early initiation of HAART after primary infection. The present study demonstrates that initiation of HAART in infected individuals as early as 10 days after the onset of symptoms of primary HIV-1 infection did not prevent generation of latently infected, resting CD4 + T cells carrying integrated HIV-1 DNA as well as infectious HIV-1 despite the successful control of plasma viremia shortly after institution of HAART. Furthermore, there was no correlation between either the duration of HAART at the time of study (range: 0.2–17 months) or the time of initiation of HAART after the onset of symptoms of primary HIV-1 infection (range: 0.3–4 months) and the frequencies of resting CD4 + T cells carrying either integrated HIV-1 DNA or infectious virus. These results underscore the rapidity with which latent reservoirs are established in primary HIV-1 infection and indicate that it is unlikely that early treatment during primary infection can prevent establishment of a pool of latently infected, resting CD4 + T cells as long as treatment is initiated after plasma viremia becomes evident.