Persistent HIV RNA shedding in semen despite effective antiretroviral therapy

Department of Medicine, Dalla Lana School of Public Health, Toronto, Ontario, Canada.
AIDS (London, England) (Impact Factor: 5.55). 09/2009; 23(15):2050-4. DOI: 10.1097/QAD.0b013e3283303e04
Source: PubMed

ABSTRACT Effective antiretroviral therapy (ART) may reduce HIV sexual transmission by lowering genital HIV levels. A prospective study of men starting ART (n = 25) demonstrated rapid, substantial reductions in semen HIV RNA. However, despite an undetectable blood viral load, isolated semen HIV shedding was detected at more than one visit in 12 of 25 (48%) participants, with semen HIV RNA levels exceeding 5000 copies/ml in four of 25 (16%). Isolates were drug-sensitive, and this phenomenon was not associated with semen drug levels or regimen.

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    • "Although effective ARV therapy decreases virus in genital secretions, discordance between plasma and genital viral loads has been reported. HIV-infected males may have isolated semen HIV shedding even when plasma viral load is undetectable [94, 95] and independent of semen drug levels and ARV regimen [96]. Additionally, ARV genital tract penetration varies among ARV agents [97]. "
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    ABSTRACT: Women living with HIV have fertility desires and intentions that are similar to those of uninfected women, and with advances in treatment most women can realistically plan to have and raise children to adulthood. Although HIV may have adverse effects on fertility, recent studies suggest that antiretroviral therapy may increase or restore fertility. Data indicate the increasing numbers of women living with HIV who are becoming pregnant, and that many pregnancies are unintended and contraception is underutilized, reflecting an unmet need for preconception care (PCC). In addition to the PCC appropriate for all women of reproductive age, women living with HIV require comprehensive, specialized care that addresses their unique needs. The goals of PCC for women living with HIV are to prevent unintended pregnancy, optimize maternal health prior to pregnancy, improve maternal and fetal outcomes in pregnancy, prevent perinatal HIV transmission, and prevent HIV transmission to an HIV-uninfected sexual partner when trying to conceive. This paper discusses the rationale for preconception counseling and care in the setting of HIV and reviews current literature relevant to the content and considerations in providing PCC for women living with HIV, with a primary focus on well-resourced settings.
    Infectious Diseases in Obstetrics and Gynecology 10/2012; 2012:604183. DOI:10.1155/2012/604183
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    • "It does not appear to correlate to suboptimal drug concentrations in semen nor to any specific drug regimen, and occurs in the absence of other detectable sexually transmitted infections, known to increase the release of HIV in semen [7]. High seminal viral load before treatment initiation is to date the only factor found to correlate with persistent release of HIV in semen despite HAART [3]. Several phylogenetic studies demonstrated that HIV in semen arises from local productive sources within the MGT and/or, depending on the individuals, from passive diffusion from the blood [8], [9], [10] (previous references in [7]). "
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    ABSTRACT: 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). 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. Short 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. Our 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.
    PLoS ONE 05/2012; 7(5):e37348. DOI:10.1371/journal.pone.0037348 · 3.23 Impact Factor
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    • "HIV latency occurs in resting central memory (Tcm) and transitional memory (Ttm) CD4+ cells [89], but also in astrocytes [90, 91], monocyte-macrophages [92], naive T cells [93, 94], and thymocytes [95]. Latently infected cells can be detected in blood and tissues, such as the gastrointestinal tract [96], the central nervous system [91, 97], the genital tract [98–100], which represent “sanctuary sites”, where HAART poorly penetrates. When activated, latently infected CD4+ T cells can release the virus in the blood, even if antiretrovirals are able to prevent new rounds of infection; during HAART, these cells decay very slowly, with an average half-life of 44 months, so that under current treatment it will take over 60 years to deplete this reservoir [101]. "
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    ABSTRACT: HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important one is represented by latently infected cells. Several methods, including 2-LTR HIV DNA and unspliced HIV RNA measurement, have been developed to estimate residual viremia and predict the outcome of antiretroviral therapy. Considering that poor immunologic responders are exposed to a higher risk of both AIDS-related and non-AIDS-related diseases, there is a need of new therapeutic strategies, including immunomodulators and drugs targeting the latent viral reservoirs, in order to face residual viremia but also to "drive" the host immunologic responses.
    Clinical and Developmental Immunology 03/2012; 2012:515962. DOI:10.1155/2012/515962 · 2.93 Impact Factor
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