HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term non-progressors

Avettand-Fènoël, Véronique; Prazuck, Thiérry; Hocqueloux, Laurent; Mélard, Adeline; Michau, Christophe; Kerdraon, R.; Agoute, Eric; Rouzioux, Christine

doi:10.1097/qad.0b013e32830fbdbc

Cited by 56 publications

(40 citation statements)

References 12 publications

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“…HIV DNA in the rectum remained higher in cART-treated patients than in HIV controllers (165). Total HIV DNA in GALT correlates with total HIV DNA load in blood at different stages of the infection, both without and during treatment (139,158). This finding could partly explain the relevance of HIV DNA to HIV pathogenesis, even when measured only in blood, like the CD4 T cell count and HIV RNA load, two routine follow-up markers.…”

Section: Gut-associated Lymphoid Tissuementioning

confidence: 93%

“…4). Gastrointestinal CD4 T cells have been shown to harbor, on average, 13 times more HIV DNA than blood CD4 T cells during acute and early-stage HIV infection (151,(158)(159)(160). Non-CD4 T cells harbored less HIV DNA than CD4 T cells in the gut, but the infection level of non-T leukocytes was higher in GALT than in blood (161).…”

Section: Gut-associated Lymphoid Tissuementioning

confidence: 99%

“…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%

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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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Section: Gut-associated Lymphoid Tissuementioning

confidence: 93%

Section: Gut-associated Lymphoid Tissuementioning

confidence: 99%

Section: Gut-associated Lymphoid Tissuementioning

confidence: 99%

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

et al. 2016

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“…The results are reported either as the actual HIV DNA copy number per million cells or as 50% of the detection limit for samples in which HIV DNA was undetectable. The detection limit varied according to cell availability (27).…”

Section: Methodsmentioning

confidence: 99%

Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected Cells and Inefficient Viral Reactivation

Noël

Peña

David

et al. 2016

J Virol

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HIV establishes reservoirs of infected cells that persist despite effective antiretroviral therapy (ART). In most patients, the virus begins to replicate soon after treatment interruption. However, a low frequency of infected cells at the time of treatment interruption has been associated with delayed viral rebound. Likewise, individuals who control the infection spontaneously, so-called HIV-1 controllers (HICs), carry particularly low levels of infected cells. It is unclear, however, whether and how this small number of infected cells contributes to durable viral control. Here we compared 38 HICs with 12 patients on effective combined antiretroviral therapy (cART) and found that the low frequency of infected cells in the former subjects was associated both with less efficient viral reactivation in resting CD4؉ T cells and with less efficient virion production ex vivo. We also found that a potent HIV-specific CD8 ؉ T cell response was present only in those HICs whose CD4 ؉ T cells produced virus ex vivo. Long-term spontaneous control of HIV infection in HICs thus appears to be sustained on the basis of the inefficient reactivation of viruses from a limited number of infected cells and the capacity of HICs to activate a potent HIV-specific CD8؉ T cell response to counteract efficient viral reactivation events. IMPORTANCEThere is a strong scientific interest in developing strategies to eradicate the HIV-1 reservoir. Very rare HIV-1-infected patients are able to spontaneously control viremia for long periods of time (HIV-1 controllers [HICs]) and are put forward as a model of HIV-1 remission. Here, we show that the low viral reservoirs found in HICs are a critical part of the mechanisms underlying viral control and result in a lower probability of HIV-1 reactivation events, resulting in limited HIV-1 release and spread. We found that those HICs in whom viral reactivation and spread from CD4 ؉ T cells in vitro were the most difficult were those with diminished CD8 ؉ T cell responses. These results suggest that, in some settings, low HIV-1 reservoirs decisively contribute to at least the temporary control of infection without antiretroviral therapy. We believe that this work provides information of relevance in the context of the search for HIV-1 remission.

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“…Plasma HIV-1 RNA levels were determined on days 0 and 7 and then monthly until 6 months after transplantation. 33 The HIV-1 RNA levels were monitored every 3 months thereafter.…”

Section: Immunohistochemistry and Immunofluorescencementioning

confidence: 99%

The Kidney as a Reservoir for HIV-1 after Renal Transplantation

Canaud

Dejucq-Rainsford

Avettand-Fènoël

et al. 2014

Journal of the American Society of Nephrology

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125

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Since the recent publication of data showing favorable outcomes for patients with HIV-1 and ESRD, kidney transplantation has become a therapeutic option in this population. However, reports have documented unexplained reduced allograft survival in these patients. We hypothesized that the unrecognized infection of the transplanted kidney by HIV-1 can compromise long-term allograft function. Using electron microscopy and molecular biology, we examined protocol renal transplant biopsies from 19 recipients with HIV-1 who did not have detectable levels of plasma HIV-1 RNA at transplantation. We found that HIV-1 infected the kidney allograft in 68% of these patients. Notably, HIV-1 infection was detected in either podocytes predominately (38% of recipients) or tubular cells only (62% of recipients). Podocyte infection associated with podocyte apoptosis and loss of differentiation markers as well as a faster decline in allograft function compared with tubular cell infection. In allografts with tubular cell infection, epithelial cells of the proximal convoluted tubules frequently contained abnormal mitochondria, and both patients who developed features of subclinical acute cellular rejection had allografts with tubular cell infection. Finally, we provide a novel noninvasive test for determining HIV-1 infection of the kidney allograft by measuring HIV-1 DNA and RNA levels in patients' urine. In conclusion, HIV-1 can infect kidney allografts after transplantation despite undetectable viremia, and this infection might influence graft outcome.

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HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term non-progressors

Cited by 56 publications

References 12 publications

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

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

Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected Cells and Inefficient Viral Reactivation

The Kidney as a Reservoir for HIV-1 after Renal Transplantation

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