What Are the Implications of Poor Immunologic Response to ART?

Among patients with virologic suppression, those with initially poor immunologic response continued to have persistently low CD4-cell counts and had an increased risk for morbidity and mortality.

Most HIV-infected patients who achieve virologic success on potent antiretroviral therapy (ART) also experience adequate CD4-cell recovery. However, a small proportion do not, and the clinical implications of this discordant response to treatment have been unclear.

In this retrospective observational study, participants in the Dutch ATHENA cohort who achieved viral loads <500 copies/mL during the first 2 years on ART were divided into four groups based on their CD4 counts at 1 to 2 years (<200, 200–350, 351–500, and >500 cells/mm³). Those with CD4 counts <200 cells/mm³ were considered to have poor immunologic recovery. Outcomes of interest included a composite endpoint (cardiovascular events, AIDS, cancer, cirrhosis, or death), non–AIDS-defining diseases overall, cardiovascular events, and non–AIDS-defining malignancies specifically.

The 3068 patients included in the analysis (83% male) had a median age of 41, a median nadir CD4 count of 170 cells/mm³, and a median baseline CD4 count of 360 cells/mm³; 6.5% had poor CD4-cell recovery. Independent predictors of poor CD4-cell recovery included older age, lower nadir CD4-cell count, and lower viral load at ART initiation.

During more than 10,000 person-years of follow-up, patients with poor CD4-cell recovery had the highest frequency of the composite endpoint, non–AIDS-defining diseases overall, and cardiovascular events. A key observation was that the patients with poor immunologic recovery had a median CD4 count of only 320 cells/mm³ after 7 years of potent ART.

Comment: The low median nadir CD4 count for the entire cohort (170 cells/mm³), together with the failure of many patients to achieve CD4 counts >500 cells/mm³ after years of suppressive ART, underscores the need for expansion of HIV testing and outreach efforts. The aim of those efforts would be to identify recently infected individuals, engage them in care, and initiate potent ART at higher CD4-cell counts, thus optimizing immune recovery and clinical benefit, with decreased transmission of HIV as a likely public health bonus. Although the potential benefits of early treatment seem clear, actual experience and the current economic outlook indicate that expanding provision of care to include most individuals with new HIV diagnoses will be difficult.

Source: Journal Watch HIV/AIDS Clinical Care