HIV-1 RNA levels and CD4+T lymphocyte counts are currently the standard markers used in clinical practice for the management of HIV infection. Nowadays it is also possible to monitor the evolution of HIV infection by measuring HIV-DNA. This measurement is a useful new clinical marker mainly been used to date in experimental evaluations. HIV-DNA can be detected in lymphoid tissues and in PBMC even during powerful and prolonged antiretroviral therapy. Understanding the HIV-DNA marker, together with all the other standard markers used in clinical practice, is now essential in monitoring the progression of the infection. Furthermore, the measurement of the levels of HIV-DNA in different stages could indicate the spread of the infection reflecting the ability of antiretroviral therapy to purge reservoirs. This review highlights the importance of evaluating the HIV-DNA load which could provide an indirect estimate of the quantity of reservoirs. This is an important factor in establishing the progression of infection, sequencing therapy and predicting the failure of antiretroviral therapy at a early stage.