Short communication: no evidence of occult SHIV infection as demonstrated by CD8+ cell depletion after chemoprophylaxis-induced protection from mucosal infection in rhesus macaques.
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 SHIV(SF162P3) 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 10(6) to 10(7) 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.
Kersh
Ellen N
EN
Division of HIV/AIDS prevention, NCHHSTP, CCID, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Luo
Wei
W
Adams
Debra R
DR
Mitchell
James
J
Garcia-Lerma
J Gerardo
JG
Heneine
Walid
W
Folks
Thomas M
TM
Butera
Sal
S
Otten
Ron A
RA
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D000918:Antibody Specificity; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018890:Chemoprevention; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D000068679:Emtricitabine; D015497:HIV-1 / Q000235:genetics; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D018655:Lymphocyte Count; D008253:Macaca mulatta; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D016865:Reassortant Viruses; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000276:immunology
D019380:Anti-HIV Agents; D000906:Antibodies; D000998:Antiviral Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine