No evidence of occult SHIV infection as demonstrated by CD8+ cell depletion after chemoprophylaxis-induced protection from mucosal infection in rhesus macaques

Ellen N. Kersh, Wei Luo, Debra R. Adams, James Mitchell, J. Gerardo Garcia-Lerma, Walid Heneine, Thomas M. Folks, Sal Butera, Ron A. Otten

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Preexposure prophylaxis (PrEP) with antiretroviral drugs constitutes a promising strategy for HIV prevention. Potent PrEP regimens with reverse transcriptase inhibitors can prevent detectable SHIV infection in a repeated low-dose macaque model that resembles human transmission, supporting plans to quickly move this approach into human trials. However, the possibility remains that extremely low levels of virus replication could nonetheless occur during PrEP and seed viral reservoirs in tissues. Therefore, seemingly protected macaques may harbor occult virus that may be initially contained by cytotoxic T cells, but could emerge later. To explore this possibility, we studied whether CD8+ cells suppress viremia in four rhesus macaques apparently protected by daily or intermittent Truvada (FTC and tenofovir) during 14 low-dose, rectal SHIVSF162P3 challenges and during a subsequent drug washout period. CD8+ cells were efficiently ablated with antibodies in these and two additional control macaques that were previously infected but had reached undetectable virus set points. During 4 weeks of follow-up, all four macaques remained free of plasma viremia and provirus in blood lymphocytes. In contrast, plasma viremia resurged to 106 to 107 copies per milliliter within 2 weeks in both control macaques. Thus, these results indicate that the undetectable viremia in the PrEP-protected macaques was not due to CD8+ cells that were containing a low-level infection. Rather, the PrEP treatment created conditions in which infection was prevented, eliminated, or controlled by unknown mechanisms. These data provide important information for PrEP usage to prevent HIV transmission, and fully support the continued pursuit of PrEP prevention measures in humans.

Original languageEnglish (US)
Pages (from-to)543-546
Number of pages4
JournalAIDS Research and Human Retroviruses
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

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Chemoprevention
Macaca
Macaca mulatta
Viremia
Infection
Tenofovir
HIV
Viruses
Proviruses
Reverse Transcriptase Inhibitors
Virus Replication
Pharmaceutical Preparations
Seeds
Lymphocytes
T-Lymphocytes
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

No evidence of occult SHIV infection as demonstrated by CD8+ cell depletion after chemoprophylaxis-induced protection from mucosal infection in rhesus macaques. / Kersh, Ellen N.; Luo, Wei; Adams, Debra R.; Mitchell, James; Garcia-Lerma, J. Gerardo; Heneine, Walid; Folks, Thomas M.; Butera, Sal; Otten, Ron A.

In: AIDS Research and Human Retroviruses, Vol. 24, No. 4, 01.04.2008, p. 543-546.

Research output: Contribution to journalArticle

Kersh, Ellen N. ; Luo, Wei ; Adams, Debra R. ; Mitchell, James ; Garcia-Lerma, J. Gerardo ; Heneine, Walid ; Folks, Thomas M. ; Butera, Sal ; Otten, Ron A. / No evidence of occult SHIV infection as demonstrated by CD8+ cell depletion after chemoprophylaxis-induced protection from mucosal infection in rhesus macaques. In: AIDS Research and Human Retroviruses. 2008 ; Vol. 24, No. 4. pp. 543-546.
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