Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level

Viard, Jean‐Paul; Burgard, Marianne; Hubert, Jean‐Baptiste; Aaron, Laurent; Rabian, Cécile; Pertuiset, Nathalie; Lourenço, Maria Helena; Rothschild, Chantal; Rouzioux, Christine

doi:10.1097/00002030-200401020-00005

Cited by 154 publications

(111 citation statements)

References 12 publications

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“…The high levels of tat mRNA observed with the ART-treated HIV-2 cohort suggested that the therapeutic regimens used were unable to reduce the rate of de novo cell infection. These data contrast with those for ART-treated HIV-1 ϩ patients, in which virological response is usually associated with a sharp decline in MS mRNA (4,21,62) and in the proportion of MS mRNA relative to US mRNA in PBMC (57), as well as with a progressive decrease in proviral DNA (23,58,59) despite the low-level viremia that can frequently be detected using ultrasensitive assays (17,43).…”

Section: Discussionmentioning

confidence: 65%

“…Viremia levels were similar in the treated and untreated HIV-2 cohorts, due to the low-level viremia detected in some of the ART-treated HIV-2 ϩ patients ( Table 2). Of note, in contrast with the progressive decline in proviral DNA levels usually observed with ART-treated HIV-1 ϩ patients (23,58), proviral DNA did not significantly differ between untreated and treated HIV-2 ϩ patients (Fig. 3A), despite the prolonged treatment.…”

Section: Relationship Of Plasma and Cell-associated Viral Load With Cmentioning

confidence: 71%

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Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Soares¹,

Tendeiro

Foxall

et al. 2011

J Virol

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Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1 ؉ ) and HIV-2 ؉ individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2 ؉ patients, despite the reduced viremia (undetectable to 2.6 ؋ 10 4 RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2 ؉ patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2 ؉ patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2 ؉ patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.

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Section: Discussionmentioning

confidence: 65%

Section: Relationship Of Plasma and Cell-associated Viral Load With Cmentioning

confidence: 71%

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Soares¹,

Tendeiro

Foxall

et al. 2011

J Virol

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“…Failure of HIV DNA to decrease in 12 months post-cART in pTfh and non-pTfh cells of chronically infected patients is not surprising. It is well known that the rate of decay of cell-associated HIV DNA is fastest in patients initiating treatment very early during the acute infection, and even in these situations the decay can take up to 8 months following cART initiation (44)(45)(46). In our study, all patients were chronically HIV infected, and it is likely that HIV DNA decay takes longer than 48 weeks on cART.…”

Section: Discussionmentioning

confidence: 68%

Peripheral T Follicular Helper Cells Are the Major HIV Reservoir within Central Memory CD4 T Cells in Peripheral Blood from Chronically HIV-Infected Individuals on Combination Antiretroviral Therapy

Pallikkuth

Sharkey

Babič

et al. 2016

J Virol

112

111

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In this study, we examined the peripheral blood (PB) central memory (T CM ) CD4؉ T cell subsets designated peripheral T follicular helper cells (pTfh cells) and non-pTfh cells to assess HIV permissiveness and persistence. Purified pTfh and non-pTfh cells from healthy HIV-negative donors were tested for HIV permissiveness using green fluorescent protein (GFP)-expressing HIV-1NL4-3/Ba-L, followed by viral reactivation using beads coated with anti-CD3/anti-CD28 monoclonal antibodies. The role of pTfh cells in HIV persistence was analyzed in 12 chronically HIV-1 infected patients before and 48 weeks after initiation of raltegravir-containing combination antiretroviral therapy (cART). Total cellular HIV-1 DNA and episomes containing two copies of the viral long terminal repeat (2LTR circles) were analyzed in using droplet digital PCR in the purified pTfh and non-pTfh cells.

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“…The extraction and purification of DNA from cells were performed using a QIAamp blood kit (Qiagen, Inc., Chatsworth, CA). The real-time TaqMan protocol published by Viard and colleagues (29) was used to quantify the cellular HIV DNA copy number in PBMCs. The cell line 8E5, which contains one copy of integrated HIV DNA in each cell, was used to build a standard curve, with a sensitivity of 5 copies/million PBMCs (21).…”

Section: Methodsmentioning

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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Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level

Abstract: These results question the benefit of very long-term maintenance of HAART in terms of CD4 gain and HIV-1 DNA reduction.

Cited by 154 publications

References 12 publications

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Peripheral T Follicular Helper Cells Are the Major HIV Reservoir within Central Memory CD4 T Cells in Peripheral Blood from Chronically HIV-Infected Individuals on Combination Antiretroviral Therapy

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

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