Association between Cellular Human Immunodeficiency Virus DNA Level and Immunological Parameters in Patients with Undetectable Plasma Viremia Level during Highly Active Antiretroviral Therapy

Sarmati, Loredana; Parisi, Saverio Giuseppe; Nicastri, Emanuele; d’Ettorre, Gabriella; Palmisano, Lucia; Andreotti, Mauro; Andreoni, Carolina; Giuliano, Marina; Gatti, Francesca; Boldrin, Caterina; Palù, Giorgio; Vullo, Vincenzo; Vella, Stefano; Andreoni, Massimo

doi:10.1128/jcm.43.12.6183-6185.2005

Cited by 21 publications

(11 citation statements)

References 12 publications

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“…Low levels of ongoing, persistent HIV replication may contribute to the longevity of the latent viral reservoir by continually fuelling new rounds of infection in resting CD4 + T cells. The quantification of HIV DNA in peripheral blood cells, in addition to RNA viral load in patients' plasma, may be extremely important for disease monitoring, especially in HAART-treated patients [23,27,[37][38][39], when RNA viral load is undetectable by current techniques [25,30,40,41]. This report studied total and 2-LTR circular HIV-1 DNA proviral load, by SYBR Green-based real-time PCR, a useful and reliable approach for determining genome regions with a high mutation rate [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

HIV-1 DNA proviral load in treated and untreated HIV-1 sero-positive patients

Re¹,

Vitone²,

Biagetti

et al. 2010

Clinical Microbiology and Infection

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As proviral human immunodeficiency virus type 1 (HIV-1) DNA can replenish and revive viral infection upon activation, its detection might offer significant therapeutic information, complementing the input provided by plasma RNA determination in the follow-up of infected individuals. A selected group of acutely infected subjects was studied to verify both total and 2-long terminal repeat (2-LTR) DNA proviral load during the acute phase of infection and thereafter. Patients were divided in two sex- and age-matched groups: 19 naive individuals who did not receive antiretroviral therapy during the observation period and 20 subjects treated according to current guidelines. Total and 2-LTR HIV-1 DNA proviral load, in addition to RNA viral load and CD4 cell count, were determined in peripheral blood mononuclear cells (PBMC) at baseline, 6 and 12 months after the first sampling. Total and 2-LTR HIV-1 DNA proviral load exhibited no significant variation at any time in the naive patients (total HIV-1 DNA ranging from 896 + or - 731 to 715 + or - 673 copies/10(5) PBMC and 2-LTR HIV-1 DNA ranging from 94 + or - 105 to 65 + or - 44 copies/10(5) PBMC), whereas a significant reduction in both total HIV-1 DNA (ranging from 997 + or - 676 to 262 + or - 174 copies/10(5) PBMC) and 2-LTR HIV-1 DNA proviral load (ranging from 116 + or - 55 to 26 + or - 35 copies/10(5) PBMC) was detected in highly active antiretroviral therapy (HAART) patients, together with a CD4(+) T cell count increase and RNA load decrease. HAART negatively affects both the labile HIV burden and the integrated proviral DNA, at least in the initial period of successful treatment, suggesting that quantification of HIV-1 DNA proviral load may be an important parameter in monitoring HIV infection.

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Section: Discussionmentioning

confidence: 99%

HIV-1 DNA proviral load in treated and untreated HIV-1 sero-positive patients

Re¹,

Vitone²,

Biagetti

et al. 2010

Clinical Microbiology and Infection

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show abstract

“…A lower HIV DNA load after a defined duration of HAART was significantly related to a higher pre-HAART CD4 cell count and percentage and a prolonged duration of antiretroviral treatment (2,19,27,30). Furthermore, the absence of previous exposure to antiretroviral therapy was a predictive factor for larger decreases in cellular HIV-1 DNA levels (19).…”

Section: Discussionmentioning

confidence: 99%

Baseline Cellular HIV DNA Load Predicts HIV DNA Decline and Residual HIV Plasma Levels during Effective Antiretroviral Therapy

et al. 2012

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Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a marker of disease progression with significant predictive power, but published data on its correlation with plasma HIV RNA levels and CD4 counts in acute and chronic patients are not conclusive. We evaluated a cohort of 180 patients naïve for antiretroviral therapy before the beginning of treatment and after a virological response in order to define the indicators correlated with HIV DNA load decrease until undetectability. The following variables were evaluated as continuous variables: age, CD4 cell count and log 10 HIV DNA level at baseline and follow-up, and baseline log 10 HIV RNA level. Primary HIV infection at the start of therapy, an HIV RNA level at follow-up of <2.5 copies/ml, origin, gender, and transmission risk were evaluated as binary variables. The decline of HIV DNA values during effective therapy was directly related to baseline HIV DNA and HIV RNA values, to an increase in the number of CD4 cells, and to the achievement of an HIV RNA load of <2.5 copies/ml. An undetectable cellular HIV DNA load was achieved by 21.6% of patients at the follow-up time point and correlated significantly with lower baseline cellular HIV DNA values and with being in the primary stage of infection when therapy started. In conclusion, early treatment facilitated the achievement of undetectable levels of plasma viremia and cellular HIV DNA and a better recovery of CD4 lymphocytes. HIV DNA levels before and during highly active antiretroviral therapy may be used as a new tool for monitoring treatment efficacy.

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“…Several studies have shown that a lower HIV DNA load during cART is associated with better immune recovery (194,200,201). Similarly, a low HIV DNA load was found to be predictive of better immune restora-tion in children on cART (202) and was associated with CD4 cell count dynamics during cART combined with interleukin-2 (203).…”

Section: Total Hiv Dna Load During Cart Is Informative Of Patient Prementioning

confidence: 98%

“…Multivariate analysis indicated that low HIV DNA load in patients with cART for a median of 25 months was significantly associated with prolonged HIV RNA suppression on cART (194). HIV DNA load during cART was independently associated with cumulative HIV RNA viremia over the previous 5 years ( 93,192).…”

Section: Total Hiv Dna Load During Cart Is Informative Of Patient Prementioning

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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Association between Cellular Human Immunodeficiency Virus DNA Level and Immunological Parameters in Patients with Undetectable Plasma Viremia Level during Highly Active Antiretroviral Therapy

Cited by 21 publications

References 12 publications

HIV-1 DNA proviral load in treated and untreated HIV-1 sero-positive patients

HIV-1 DNA proviral load in treated and untreated HIV-1 sero-positive patients

Baseline Cellular HIV DNA Load Predicts HIV DNA Decline and Residual HIV Plasma Levels during Effective Antiretroviral Therapy

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

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