HIV RNA Suppression and Immune Restoration: Can We Do Better?

Abstract

<jats:p>HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important one is represented by latently infected cells. Several methods, including 2-LTR HIV DNA and unspliced HIV RNA measurement, have been developed to estimate residual viremia and predict the outcome of antiretroviral therapy. Considering that poor immunologic responders are exposed to a higher risk of both AIDS-related and non-AIDS-related diseases, there is a need of new therapeutic strategies, including immunomodulators and drugs targeting the latent viral reservoirs, in order to face residual viremia but also to “drive” the host immunologic responses.</jats:p>

Initial suboptimal CD4 reconstitution with antiretroviral therapy despite full viral suppression in a cohort of HIV-infected patients in Senegal

“…Since the viral load is inversely correlated to the CD4 count, this could explain the association between a higher number of initial CD4 and suboptimal recovery at six months [1]. However, other authors reported the opposite, i.e.…”

“…The recovery of the CD4 count during this process occurs in three stages. In the first six months of treatment, a fast increase of 20 to 30 CD4 cells/mm 3 per month is observed [1,2]. Nevertheless, for some patients, the immune response during this phase is insufficient despite an undetectable viral load.…”

Among Patients with Sustained Viral Suppression in a Resource-Limited Setting, CD4 Gains Are Continuous Although Gender-Based Differences Occur

“…The greatest increases in CD4 count occur during the first year of ART initiation [4,5,8,9,10], especially in patients with low baseline CD4 count [11]. However patients with low CD4 count are more likely to take longer to return to normal CD4 count levels [5], and may remain at increased risk of opportunistic infection hence morbidity [12]. Two studies in resource-rich countries with a minimum follow-up time of 6 years have shown a significant increase in CD4 count among patients who initiated ART at lower CD4 count level compared to those who started ART at high CD4 count [4,9].…”

Thymic Function during 12 Months of Highly Active Antiretroviral Therapy in Thai HIV-Infected Patients with Normal and Slow Immune Recovery

“…However, the slow immune reconstitution in SR patients was probably not due to lower baseline CD4 ＋ T-cell counts as previously described in other studies (2,3) because the baseline CD4 ＋ T-cell counts in NR and SR patients were not significantly different. Other factors such as a highly activated apoptotic T-cell compartments, residual viremia, and elevated levels of interleukin-7, a key cytokine necessary to regulate the proliferation and survival of circulating naä ƒve and memory T cells, likely influenced the lower CD4 ＋ T-cell counts in SR patients after HAART, as proposed previously (4,(13)(14)(15).…”