The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH

Since the reasons for differential immune reconstitution in HIV-infected patients are still not fully understood, we considered it reasonable to investigate whether the presence of primary HIV drug resistance mutations could be one of the factors of inadequate immune reconstitution. Evaluation of unfavorable factors of immune reconstitution can help identify patients at risk of persistently low CD4 cell counts and CD4:CD8 ratios and requiring careful monitoring for progression to AIDS.

Untreated HIV infection leads to progressive and permanent impairment of the immune system, and the successive loss of peripheral blood CD4+ T lymphocytes results in progression to AIDS. Effective antiretroviral therapy (ART) can prevent the decline and even cause the restore of the normal level of CD4+ cells. CD4+ count ≥ 500 cells/µl and CD4:CD8 ratio ≥ 1 are considered normal, while patients with persistently lower CD4+ and CD4:CD8 ratios despite ART treatment are defined as having an inadequate immune response, which may result in an increased risk progression to AIDS, and thus higher mortality rates. Clinical risk factors for impaired CD4+ regeneration have not been fully established, however, older age, male gender, low CD4+ cell count and low CD4:CD8 ratio at diagnosis are associated with a poorer immune response to ART. As well, HIV drug resistance also plays an important role in the process of immune reconstruction. Despite the very good results of ART, the emergence of drug-resistant mutations in the HIV virus, which may lead to treatment failure, is a cause for concern. The prevalence of HIV-1 drug resistance mutations reported worldwide ranges from 5% to 25%. Primary drug resistance of HIV occurs in people who have not previously been treated with ART. These people start ART treatment with a lower genetic barrier, a higher risk of virological failure and a higher risk of developing resistance to other drugs, which may lead to insufficient immune reconstruction and progression to AIDS.