title: Cell-associated viral burden provides evidence of ongoing viral replication in aviremic HIV-2-infected patients.
abstract: Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1(+)) and HIV-2(+) individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2(+) patients, despite the reduced viremia (undetectable to 2.6 × 10(4) RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2(+) patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2(+) patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2(+) patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.
authors.affiliation: Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal.
authors.forename: Rui S
authors.initials: RS
authors.lastname: Soares
authors.forename: Rita
authors.initials: R
authors.lastname: Tendeiro
authors.forename: Russell B
authors.initials: RB
authors.lastname: Foxall
authors.forename: António P
authors.initials: AP
authors.lastname: Baptista
authors.forename: Rita
authors.initials: R
authors.lastname: Cavaleiro
authors.forename: Perpétua
authors.initials: P
authors.lastname: Gomes
authors.forename: Ricardo
authors.initials: R
authors.lastname: Camacho
authors.forename: Emília
authors.initials: E
authors.lastname: Valadas
authors.forename: Manuela
authors.initials: M
authors.lastname: Doroana
authors.forename: Margarida
authors.initials: M
authors.lastname: Lucas
authors.forename: Francisco
authors.initials: F
authors.lastname: Antunes
authors.forename: Rui M M
authors.initials: RM
authors.lastname: Victorino
authors.forename: Ana E
authors.initials: AE
authors.lastname: Sousa
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015498:HIV-2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D014779:Virus Replication; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents