HIV type 1 cervicovaginal reservoirs in the era of HAART
Institute for Human Virology and Biodefense, Thomas Jefferson University, Jefferson Alumni Hall, Philadelphia, Pennsylvania 19107, USA. AIDS Research and Human Retroviruses
(Impact Factor: 2.33).
09/2005; 21(8):714-8. DOI: 10.1089/aid.2005.21.714
Highly active antiretroviral therapy (HAART) does not lead to viral eradication, due to HIV-1 residual disease. We investigated whether the cervicovaginal tract serves as a viral reservoir. Seven out of eight cervicovaginal fluids were positive for cell-free HIV-1, by supersensitive reverse transcriptase-polymerase chain reactions (RT-PCR), with a detection limit of 1 copy/ml. No viral outgrowth, intracellular proviral DNA, or viral RNA was detected from cervicovaginal lavage and ecto- and endocervical cells. The cervicovaginal tract of patients on HAART is likely not a major solid tissue reservoir for HIV-1. Nonetheless, the presence of even low cell-free HIV-1 RNA in cervicovaginal secretions continues to suggest the importance of practicing protected sex, even in the era of HAART.
Available from: Michelino Di Rosa
- "HIV latency occurs in resting central memory (Tcm) and transitional memory (Ttm) CD4+ cells , but also in astrocytes [90, 91], monocyte-macrophages , naive T cells [93, 94], and thymocytes . Latently infected cells can be detected in blood and tissues, such as the gastrointestinal tract , 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 . "
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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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ABSTRACT: This review provides recent information relating to how monocytes and macrophages contribute to persistence of HIV-1 in individuals with highly active antiretroviral therapy-induced viral suppression.
The restriction factor APOBEC-3G after entry is present in an active form in monocytes but not macrophages, providing an explanation for why monocytes are less susceptible to HIV-1 infection than macrophages. A subset of monocytes is, however, more susceptible to HIV-1 infection than the majority of blood monocytes. New techniques allow distinction between stably integrated and unintegrated forms of HIV DNA, resulting in demonstration that rebounding HIV-1 is genetically distinct to virus in the T-cell latent reservoir. Controversy has ended by showing that extrachromosomal 2-LTR circles are stable in terminally differentiated monocytes/macrophages but represent ongoing viral replication in proliferating cells. Infectious virions are present in cytoplasmic compartments for prolonged periods of time, thus supporting the role of these cells as a source of viral persistence. Whilst the intestinal macrophage is not likely to provide a source of viral persistence, residual infection can be detected in the genital tract and brain macrophages in individuals on highly active antiretroviral therapy. Antiretroviral drug resistance may emerge more slowly in monocytes/macrophages than in T cells, as recently demonstrated for lamivudine.
Although many questions are still unanswered, there is increasing recognition that latent T-cell reservoirs cannot fully explain the failure of highly active antiretroviral therapy to eradicate HIV-1 and that monocytes/macrophages play a critical role as a source of residual infection.
Current opinion in HIV and AIDS 04/2006; 1(2):129-33. DOI:10.1097/01.COH.0000209583.89952.9d · 4.68 Impact Factor
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ABSTRACT: To delineate the fundamental aspects of HIV-1 in genital secretions such as virus origins, dynamics, and modifiable factors and their effects on viral reservoirs in the male and female genital compartments.
The transmission rate of HIV-1 per sexual encounter is relatively small. Male and female genital tissues secrete distinct cell-free and cell-associated HIV-1 quasispecies that are different from the populations present in the blood. Cell-free and cell-associated HIV-1 in the genital compartment originates from discrete tissues in the male and female genital regions rather than from the blood. Recent findings indicate that compartmentalization is maintained through immune response pressures on viral selection. HIV-1 clearance rates after therapy, and thus HIV-1 replication, in the male genital organ is slower than that in blood. Furthermore, higher concentrations of latently infected cells are found in the semen compartment compared with the blood compartment.
Viral populations in genital tissues respond to therapy differently to those present in blood. This would suggest that the genital and blood compartments probably serve as distinct reservoirs harboring latent HIV-1 during prolonged drug therapy. Understanding transmission at these sites, as well as the different viral and environmental replication characteristics and the tissue sites of virus origin in these compartments is vital to creating better treatment and prevention regimens.
Current opinion in HIV and AIDS 04/2006; 1(2):97-102. DOI:10.1097/01.COH.0000200507.27578.26 · 4.68 Impact Factor
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