Virological response after short-term CCR5 antagonist exposure in HIV-infected patients: frequency of subjects with virological response and associated factors

Abstract

The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response was considered positive if either a reduction of ≥1-log(10) HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels were determined by using patients' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4(+) T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response after short-term maraviroc exposure. Lower CD4(+) T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists should be an early treatment option before the expansion of CXCR4-tropic strains.

Fig. 1.

Frequency of virological response after MCT. (a) Percentage of subjects with a virological response after a short-term MRV exposure (MCT positive). Black bar, percentage of MCT-positive subjects in the total population. The population was also split into pretreated and treatment-naïve subjects (gray bars). (b) Percentage of MCT-positive subjects depending on different baseline CD4⁺ T-cell strata. Black bars, total number of subjects; gray bars, treatment-naïve subjects. We did not observe any treatment-naïve subjects in the lower CD4⁺ T-cell strata (<100 and 100 to 199 cells/μl).

Fig. 2.

X4- and R5-tropic virus levels and CD4⁺ T-cell levels depending on treatment category. Log viral loads in the U87-X4 and U87-R5 well supernatants were used to express X4- and R5-tropic virus levels. (a) MCT-positive patients (n = 39) presented significantly lower X4-tropic virus levels than MCT-negative patients (n = 18); (b) R5-tropic virus levels were similar in patients with different responses after MCT; (c) treatment-naïve patients (n = 9) presented a trend toward lower X4-tropic virus levels than pretreated patients (n = 48); (d) in addition, treatment-naïve patients (n = 19) showed higher CD4⁺ T-cell levels than pretreated patients (n = 71); (e) patients with the lower CD4⁺ T-cell strata (<100 CD4⁺ T cells/μl [n = 11] and 100 to 199 CD4⁺ T cells/μl [n = 11]) presented significantly higher X4-tropic virus levels than patients with higher CD4⁺ T-cell strata (200 to 350 CD4⁺ T cells/μl [n = 15] and >350 CD4⁺ T cells/μl [n = 20]); (f) on the contrary, R5-tropic virus levels were independent of the CD4⁺ T-cell strata. Black bars, median. The Mann-Whitney U test was used.