Background: HIV-1-infected men on suppressive highly active antiretroviral therapy(HAART) have a reduction of viral replication in vivo, but HIV-1 RNA is still detectableby certain ultrasensitive reverse transcriptase±PCR assays in blood plasma. Replication-competentvirus can also be isolated from both peripheral blood mononuclearcells (PBMC) and seminal cells of these patients. Despite HAART, on-going in vivoinfection of HIV-1-seropositive patients' PBMC was demonstrated by the detection ofepisomal HIV-1 moieties, known as HIV-1 two-long terminal repeat (2-LTR) DNAcircles.Methods: The present study analyzes whether new cellular infections occur in vivo inseminal cells of HIV-1-infected men on suppressive HAART. PBMC and seminal cellswere isolated from a cohort of HIV-1-seropositive men taking suppressive HAART(, 50 copies HIV RNA/ml blood plasma). Viral growth assays were performed in vitro,as well as semi-quantitative PCR to detect HIV-1 2-LTR circular DNA in PBMC andseminal mononuclear cells.Results: Viral growth in vitro was demonstrated in 16 out of 28 (57%) patients' PBMC,and in ®ve patients' seminal cells (18%). Although 18 patients' PBMC were positivefor HIV-1 2-LTR DNA circles, importantly, 2-LTR circular DNA was not detected in anysemen sample, even when replication-competent HIV-1 virus had been recoveredfrom a patient's seminal cells by viral co-culture assays.Conclusions: The current study suggests that in HIV-1-infected men treated withsuppressive HAART, new cellular infections occur in PBMC, but that new infectionsdo not take place in seminal cells in vivo. Thus, these ®ndings suggest that mainlylatent HIV-1 occurs in seminal cells of men on suppressive HAART, which may be acompartment-speci®c mechanism of residual HIV-1 disease.
Residual HIV-1 disease in seminal cells of HIV-1-infected men on suppressive HAART: latency without on-going cellular infections
Giuseppe NunnariPrimo
;
2002-01-01
Abstract
Background: HIV-1-infected men on suppressive highly active antiretroviral therapy(HAART) have a reduction of viral replication in vivo, but HIV-1 RNA is still detectableby certain ultrasensitive reverse transcriptase±PCR assays in blood plasma. Replication-competentvirus can also be isolated from both peripheral blood mononuclearcells (PBMC) and seminal cells of these patients. Despite HAART, on-going in vivoinfection of HIV-1-seropositive patients' PBMC was demonstrated by the detection ofepisomal HIV-1 moieties, known as HIV-1 two-long terminal repeat (2-LTR) DNAcircles.Methods: The present study analyzes whether new cellular infections occur in vivo inseminal cells of HIV-1-infected men on suppressive HAART. PBMC and seminal cellswere isolated from a cohort of HIV-1-seropositive men taking suppressive HAART(, 50 copies HIV RNA/ml blood plasma). Viral growth assays were performed in vitro,as well as semi-quantitative PCR to detect HIV-1 2-LTR circular DNA in PBMC andseminal mononuclear cells.Results: Viral growth in vitro was demonstrated in 16 out of 28 (57%) patients' PBMC,and in ®ve patients' seminal cells (18%). Although 18 patients' PBMC were positivefor HIV-1 2-LTR DNA circles, importantly, 2-LTR circular DNA was not detected in anysemen sample, even when replication-competent HIV-1 virus had been recoveredfrom a patient's seminal cells by viral co-culture assays.Conclusions: The current study suggests that in HIV-1-infected men treated withsuppressive HAART, new cellular infections occur in PBMC, but that new infectionsdo not take place in seminal cells in vivo. Thus, these ®ndings suggest that mainlylatent HIV-1 occurs in seminal cells of men on suppressive HAART, which may be acompartment-speci®c mechanism of residual HIV-1 disease.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
