Antiretroviral therapy is currently the primary approach to immune restoration. When HIV replication is suppressed with effective treatment, immune cells can escape infection and carry out their normal functions. Over time, if HIV remains under control, some people can achieve good immune recovery with nearly normal CD4 cell counts. However, immune recovery is a gradual process that varies considerably from person to person.

Immune restoration is sometimes regarded as a secondary aim of antiretroviral treatment, after controlling viral load. Yet research clearly shows that increasing CD4 cell counts and improvement in other immune parameters leads to better health and fewer opportunistic illnesses, regardless of viral load.

After starting antiretroviral therapy, the usual pattern is for patients to experience the most dramatic CD4 cell count increases during the first few months of treatment, followed by a more gradual increase during subsequent months and years. A number of studies have found that CD4 cell increases tend to level off or ‘plateau’ over time - generally two to five years - but others, show a continued steady, slow increase ^[1][2].

The initial rapid increase in CD4 T-cells is thought to be largely due to redistribution of existing cells from the lymph nodes into the bloodstream. Later, new CD4 cells are produced, consisting of both ‘memory’ cells that are primed to respond to specific antigens encountered in the past, and ‘naive’ cells that can respond to new pathogens. These types of T-cells are described in Memory, naive and activated T-cells in How the immune system works.

Many of the new CD4 cells appear to result from ‘clonal expansion’ or division of existing memory and naive T-cells to produce identical daughter cells. In addition, evidence indicates that completely new naive T-cells continue to be produced in the bone marrow and mature in the thymus in HIV-positive adults, even though it was traditionally believed that thymus function deteriorates after childhood ^[3].

With regard to clinical outcomes, once CD4 cell counts reach high enough levels, patients have a reduced risk for opportunistic infections and usually can stop taking prophylactic drugs. For further information, see Immune recovery and opportunistic infection prophylaxis. Studies also show that CD4 cell recovery is associated with improved overall health and survival. However, immune recovery can take a long time, especially in people who reached very low CD4 cell counts before starting anti-HIV treatment.