HIV-1–specific CD8+ T cells can mature to memory in patients receiving ART
We extended the analysis to 11 patients receiving ART with a good clinical response, as noted by a reduction of viral replication to undetectable levels and an increase in absolute CD4+ T cell counts. PVLs, as measured by the Ultrasensitive assay, were <50 HIV RNA copies/mL for all 11 patients at the time of the phenotype assay. The minimum length of time that a patient had been receiving ART at the time of the T cell phenotype assay was 1 month, although most patients had been receiving ART for >1 year
The tetramer-positive cells for these donors were virtually all CD27+; therefore, only the CD45RA and CD28 analysis is shown. For 6 of the 11 patients (patients 4480, SP1549, 1602,1549, 1596, and 4496), the acute-phase phenotype predominated. However, 1 of these patients (patient 1602) showed a relatively reduced percentage of cells found in the acute subset, which was accompanied by an increase in the percentage of cells in the intermediate subset. For 5 of the 11 patients (patients 4170, 1551, 6455, 1604, and 1552), >40% of the tetramer-positive cells were memory. Three of these 5 patients (patients 1551, 6455, and 1604) had subset distributions that were similar to that found on average for EBV in healthy volunteers. One patient, patient 1552, had a subset distribution that was similar to that found on average for FLU, with 75% of the tetramer-positive cells having matured to memory.
Monthly Amplicor and Ultrasensitive PVL measurements were available over a 3–4-year period for 6 of these 11 patients (patients 1602, 1549, 1596, 1551, 1604, and 1552). The lower limits of quantification for these tests are 400 HIV RNA copies/mL and 50 HIV RNA copies/mL, respectively.
These 6 patients divided evenly as to whether they were primarily of an acute or memory phenotype. Two of the 3 patients with responses of a primarily acute phenotype (patients 1549 and 1596) had frequent positive Ultrasensitive test results throughout the 3–4–year period and positive Ultrasensitive tests within 2–7 months of the phenotypic analysis. The third patient with a primarily acute phenotype, patient 1602, had 1 positive Ultrasensitive test 15 months before phenotypic analysis. For the 3 patients with shifts toward memory, the last positive Ultrasensitive test was 21–30 months before phenotypic analysis. Therefore, those individuals with either multiple-positive Ultrasensitive tests and/or a positive test relatively close to the time of the subset analysis were the individuals with responses primarily of the acute expansion phenotype.