HIV-1 DNA load in naive and successful antiretroviral treated patients

Abstract number: 1134_01_259

Parisi S.G., Nicastri E., Mazzi R., Gatti F., Concia E., Boldrin C., Biasolo M., Palù G., Andreoni M.

Objectives:  

In antiretroviral treated patients the size of the HIV DNA reservoir in PBMCs is associated with disease progression. This parameter can be relevant for treatment maintenance, simplification or discontinuation in patients with viro-immunological success after several years on highly active antiretroviral therapy (HAART). We evaluated the association between HIV-DNA load and viro-immunologic and clinical parameters in antiretroviral naive (NPts) and in treated (TrPts) patients, selected for successful long term HAART.

Methods:  

This cross-sectional study was performed on 31 NPts and 49 TrPts selected on the basis of plasma RNA load (50 cp/ml within 6 months of starting their first regimen, without either replication (blips) or treatment interruption, and a (12 months treatment period. To quantify the HIV-DNA integrated copy number in PBMC, we used a real time PCR in-house protocol performed on ABI-PRISM 7000 (App. Bios.), with a detection limit of 20 cp/106 CD4.

Results:  

Considering NPts stratified according to the median HIV-DNA level of 27299 cp/106 CD4 (range 189–525675), subjects with lower DNA level had more frequently higher CD4 (p = 0.042), and higher CD4 percentage (p = 0.13). No statistically significant association with plasma RNA levels was found. After a median of 30 months of HAART (12–93 months), 6 out of 49 (12.2%) patients had undetectable DNA level. Considering TrPts stratified according to the median DNA level (1908 cp/106 CD4), no statistically significant differences in terms of age, gender, risk factors for HIV, pre-HAART HIV-RNA level, PI- or NNRTI-based HAART, duration of HAART were found. Conversely, subjects with lower HIV-DNA level had more frequently higher pre-HAART CD4 cell count and percentage, higher CD4 cell count and percentage at last follow up (p < 0.001 for all assays). Considering TrPts by CD4 count strata (<200, 201–350, >350), the distribution of HIV-DNA load was statistically correlated in these groups (p < 0.001). After adjusting for epidemiological and other confounding variables, only pre-HAART CD4 cell count (OR 0.1, 95% CI 0.01–0.92, p < 0.001) was found to be independently associated to low DNA values.

Conclusions:  

In NPts HIV-DNA load was inversely correlated with immunological status, but not with RNA load. Patients with persistently undetectable RNA load during HAART have a wide range of proviral DNA (<20–13142 cp/106 PBMC). Low DNA level was independently associated with high pre-HAART CD4 cell count.