This study assessed factors associated with HIV-DNA levels in chronically infected patients on long-term suppressive antiretroviral therapy. This was a cross-sectional, multicentre study of patients receiving ART for more than 3 years, HIV-RNA less than 50 copies/ml for more than 2 years and CD4 cell count more than 350 cells/ml. Factors associated with low (<150) or high (>1000), compared with intermediate (150–1000 copies/10⁶ PBMC) levels of HIV-DNA were investigated using multinomial logistic regression.

522 patients who initiated ART during the chronic phase were included (71% male; median peak HIV-RNA: 4.88 log 10 copies/ml, CD4 cell count nadir: 222 cells/ml). Median ART duration was 13 years [interquartile range (IQR) 7–17], viral suppression was 5.7 years (IQR 3.9–8.5) and 66% of the patients never experienced ART failure. Median HIV-DNA was 323 copies/10⁶ PBMCs (IQR, 129–717) with low, intermediate and high levels observed in 28.3, 55.4 and 16.3%, respectively. In multivariable analysis, women were more likely to achieve a low level of HIV-DNA. Each additional year with suppressed HIV-RNA increased the likelihood of low level and decreased the likelihood of high level of HIV-DNA. Peak HIV-RNA higher than 5 log₁₀ c/ml was always associated with a decreased risk of low and an increased risk of high HIV-DNA. For patients with peak HIV-RNA lower than 5 log₁₀ c/ml, past ART failure was associated with high level of HIV-DNA.

After a median duration of 13 years of ART, HIV-DNA level was still associated with peak viral load, and low level of HIV-DNA was more likely to be observed with longer duration of suppressed viremia. Avoiding any rebound in viral load while on ART is paramount.

In conclusion, chronically HIV-infected patients with long-term suppressive ART can achieve low total HIV-DNA but one over six still presented HIV-DNA above 1000 copies/10⁶ PBMCs despite long-term viral suppression.