Abstract
BackgroundThe male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2–4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs.Methodology/Principal FindingsShort term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs.ConclusionsOur results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.
Highlights
Active antiretroviral therapy (HAART) significantly improved the clinical outcome among HIV-infected patients, leading in most patients to undetectable viremia (i.e. ,50 copies/ ml)
Our results indicate that the established infection of male genital organs is not greatly impacted by short term Highly active antiretroviral therapy (HAART), whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract
Further investigations are needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART
Summary
Active antiretroviral therapy (HAART) significantly improved the clinical outcome among HIV-infected patients, leading in most patients to undetectable viremia (i.e. ,50 copies/ ml). Persistent shedding of HIV RNA and infectious particles is detected in the semen of a subset of chronically-infected men under prolonged effective HAART [1,2,3,4,5,6] (other references in [7]) In some of those men, the seminal viral load can reach several log of magnitude, despite undetectable virus in blood for years [1,3,4,5,7]. The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). This study investigates the impact of short term HAART (2–4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs
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