The intestinal mucosa as a reservoir of HIV-1 infection after successful HAART

Belmonte, Liliana; Olmos, Martı́n; Fanin, Ana; Parodi, Cecilia; Baré, Patricia; Concetti, Hugo; Pérez, Hector; Bracco, M; Cahn, Pedro

doi:10.1097/qad.0b013e3282efb74b

Cited by 61 publications

(47 citation statements)

References 10 publications

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“…We hope that our studies generate interest in the ts1 mouse as a model for HIV-1-induced thymic and intestinal infection and T cell death. Under conventional HAART therapy regimens, the intestine can serve as a viral reservoir, allowing gastrointestinal symptoms to continue despite control of viral load in the blood [50]. If GVT actually re-sets the redox tone in the ts1-infected mouse intestine, as it apparently does in the thymus [25], then repopulation of the intestinal T cell compartment could be possible, either from autologous bone marrow or allogeneic bone marrow or stem cell grafting.…”

Section: Discussionmentioning

confidence: 99%

The drug monosodium luminol (GVT) preserves crypt-villus epithelial organization and allows survival of intestinal T cells in mice infected with the ts1 retrovirus

et al. 2009

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Section: Discussionmentioning

confidence: 99%

The drug monosodium luminol (GVT) preserves crypt-villus epithelial organization and allows survival of intestinal T cells in mice infected with the ts1 retrovirus

et al. 2009

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“…A recent study of patients with acute infection showed that HIV DNA in the gut was significantly lower at Fiebig stage I than at Fiebig stages II to IV (79). The HIV DNA load in GALT declines after cART initiation (78) but does not disappear (150,158,163,164), and HIV DNA levels vary at different gut sites (151,(158)(159)(160)(161). Memory effector cells harbored the most HIV DNA in the ileum and rectum (161).…”

Section: Gut-associated Lymphoid Tissuementioning

confidence: 99%

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

et al. 2016

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SUMMARYHIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis.

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“…The four animals had varying levels of pVL prior to antiretroviral therapy. We included animals with both low pVL and higher pVL (1) to assess decay of tissue reservoirs (i.e., the GALT), as it is known that even when pVLs are undetectable in peripheral blood, replicating virus is consistently found in tissues such as GALT, 3,16,25,26 and (2) to evaluate immune restoration and activation, because even in LTNP, gut immune CD4…”

Section: Discussionmentioning

confidence: 99%

Effect of Combination Antiretroviral Therapy on Chinese Rhesus Macaques of Simian Immunodeficiency Virus Infection

Ling

Rogers²,

Johnson³

et al. 2013

AIDS Research and Human Retroviruses

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Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (< 30 vRNA copies/ml plasma) with cART in such models. As ease of viral suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to < 30 copies/ml upon initiation of cART. Cell-associated SIV DNA levels in lymphocytes from the gut were also significantly reduced. Jejunal and colonic CCR5 + CD4 + mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to < 30 vRNA copies/ml in SIVmac239-infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

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The intestinal mucosa as a reservoir of HIV-1 infection after successful HAART

Cited by 61 publications

References 10 publications

The drug monosodium luminol (GVT) preserves crypt-villus epithelial organization and allows survival of intestinal T cells in mice infected with the ts1 retrovirus

The drug monosodium luminol (GVT) preserves crypt-villus epithelial organization and allows survival of intestinal T cells in mice infected with the ts1 retrovirus

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

Effect of Combination Antiretroviral Therapy on Chinese Rhesus Macaques of Simian Immunodeficiency Virus Infection

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