HIV-1 Residual Viremia and Proviral DNA in Patients with Suppressed Plasma Viral Load ( < 400 HIV-RNA cp/ml) During Different Antiretroviral Regimens

Abstract

Low levels of plasma viremia (below 50 copies/ml of HIV-1 RNA) can be detected in the majority of HIV+ subjects successfully treated with HAART. Aim of our study was to evaluate the impact of different antiretroviral regimens on this residual viremia and on proviral HIV-1 DNA in HAART-treated subjects with plasma HIV RNA <400 cp/ml and no history of virological failure. To this purpose, a cross-sectional analysis of 319 HIV-positive patients on HAART with plasma HIV RNA <400 cp/ml was performed. Subjects had been on HAART for a median of 3.6 years: the current regimen included two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI) in 104 (32.6%) cases, of which 73 treated with a boosted PI; two NRTIs plus a non-NRTI (NNRTI) were prescribed in 166 (52.2%) cases, and NRTIs-only in 49 cases (15.4%). Patients treated with PI had the lowest nadir CD4 cell count (237+191 cells/microl) compared to patients treated with NNRTI (384+192 cells/microl) or NRTIs-only (387+222 cells/microl). Cell-associated HIV-1 DNA was measured in 231 subjects. Residual viremia was measured in 238 subjects with plasma HIV-1 RNA levels < 50 copies/ml. Multivariate analysis showed that the use of NNRTI was independently associated to low levels of residual viremia and high levels of HIV-1DNA, whereas the use of PI was independently associated to low levels of HIV-1 DNA. The better virological performance of NNRTI in terms of low residual viremia is consistent with specific literature data, whereas the greater impact of PI on the viral reservoirs is noteworthy and needs further investigations.

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

“…More potent effects on residual viremia have been demonstrated with the use of NNRTIs than with protease inhibitors (5,21), and a better performance of nevirapine than efavirenz has been suggested (5,13). In this study, no significant association was demonstrated between HAART composition and undetectable levels of HIV DNA.…”

“…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).…”

“…Plasma samples were obtained from blood that had been collected, frozen at Ϫ80°C within 6 h of collection, and kept at this temperature until tested. Residual viremia was quantified using an ultrasensitive method based on a modified Amplicor HIV-1 Monitor test, version 1.5 (Roche Molecular Systems, Branchburg, NJ), with a limit of detection of 2.5 copies/ml (21). Modifications included pelleting viruses from 2 ml of plasma at 23,600 ϫ g at 4°C for 2 h, adding half of the normal volume of the quantification standard, and resuspending the RNA pellet in 50 l of diluent.…”

Standardization and performance evaluation of “modified” and “ultrasensitive” versions of the Abbott RealTime HIV-1 assay, adapted to quantify minimal residual viremia

“…For example, i. MRV can persist for years despite of suppressive ART 4 ; ii. different ART regimens may suppress MRV at different levels 18,25,26 and the patient susceptibility to certain HIV inhibitors seems to be different, depending also on HIV-1 subtypes, previous antiretroviral experience and duration of HIV-infection 27 ; iii. intensification of ART generally does not abolish MRV 12,23,24,28 ; iv.…”

A stable CC-chemokine receptor (CCR)-5 tropic virus is correlated with the persistence of HIV RNA at less than 2.5 copies in successfully treated naïve subjects

“…The real-time TaqMan protocol was used to quantify the cellular HIV DNA copy number in PBMCs as previously described [20]. 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]. …”