The Effect of Protease Inhibitor-Based Dual Antiretroviral Regimens on CD4/CD8 Ratio During the First Year of Therapy in ART-Naïve Patients With HIV-Infection

MI Figueroa; A Camiro-Zuñiga; PF Belaunzaran-Zamudio; J Sierra Madero; J Andrade Villanueva; JR Arribas; JR Lama; DM Cecchini; G Lopardo; B Crabtree-Ramírez; A Gun; P Patterson; VI Fink; OG Sued; P Cahn

Disclosures

HIV Medicine. 2021;22(4):254-261. 

In This Article

Results

Characteristics of the Study Population

We included 571 patients (292 on DT and 279 on TT), of whom 268 (91.78%) on DT and 243 (87.10%) on TT completed 48 weeks of follow-up (P = 0.189) for the primary analysis. We summarize the baseline characteristics in Table 1. We did not identify any significant differences between groups.

CD4/CD8 Ratio at Week 48

CD4 and CD8 cell counts showed no significant differences at week 48 by treatment groups, with the median CD4 count in the DT group being 562 vs. 554 cells/μL in the TT group (P = 0.259) and median CD8 counts being 897 and 858 cells/μL, respectively (P = 0.442) (see Figure 1a). Hence, median CD4/CD8 ratios showed no differences by treatment group at week 48 (DT, 0.632 vs. TT, 0.617; P = 0.936) (see Figure 1b). Similarly, the proportion of patients with CD4/CD8 ratio > 1 was 17.9% in the DT group and 19.3% in the TT group (P = 0.678) as shown in Table 2. There were no differences in the percentage of patients that achieved a CD4/CD8 ratio > 0.5 at week 48 (DT, 52.57% vs. TT, 52.22%; P = 0.940).

Figure 1.

CD4 and CD8 medians and CD4/CD8 median ratio across time.

CD4 and CD8 Patterns Over Time

We show median CD4 and CD8 cell counts at each time point in Figure 1a. We did not observe any clinically significant differences at any time point. Nonetheless, patients receiving DT had a transitory yet significant, slightly higher median increase in CD8 counts during the first 12 weeks after ART initiation. At baseline, patients in the DT group had a median CD8 count of 993 vs. 950 cells/μL in the TT group (P = 0.135); these remained higher at week 12 (1024 vs. 936 cells/μL , P = 0.036). At week 24 (1000 vs. 945 cells/μL, P = 0.192) and onwards, this difference decreased further (week 36: 929 vs. 876 cells/μL, P = 0.276; and week 48: 897 vs. 858 cells/μL, P = 0.442). Using multi-level models, we compared CD4 and CD8 trajectories showing no differences in CD4, CD8 and CD4/CD8 ratios between treatment groups over the 48 weeks of follow-up. Median increase in CD4/CD8 ratio from baseline to week 48 was similar between both groups (0.273 vs. 0.261, P = 0.125). In the subgroup analyses, we did not identify any differences in the proportion of patients achieving CD4/CD8 ratios > 1 at 48 weeks of follow-up (Table 3).

Baseline Characteristics Associated With a CD4/CD8 Ratio > 1

In the multivariate analysis, baseline CD4 cell count was the most important predictive factor associated with attaining a CD4/CD8 ratio > 1 by week 48 [CD4 count, 201–350 cells/μL, adjusted odds ratio (aOR) = 8.717, P = 0.038, 95% confidence interval (95% CI): 1.125–67.553; CD4 count > 350 cells/μL, aOR = 53.308, P < 0.001, 95% CI: 7.119–399.184). Having a viral load > 100 000 copies/mL at baseline was also independently associated with achieving a CD4/CD8 ratio > 1 (aOR = 1.929, P = 0.049, 95% CI: 1.002–3.714) (Table 4).

CD4/CD8 Ratio at 96 Weeks of Follow-up in GARDEL Study Patients

We included all 280 patients that completed the 96-week follow-up period for this sub-analysis. This included 155 patients from the DT group and 125 from the TT group (P = 0.016). The analysis showed a slight increase in the CD4/CD8 ratio of the DT arm when compared with the TT arm, although no statistically significant differences among both groups were found, neither in the median CD4/CD8 ratio (0.688 vs. 0.663, P = 0.626) nor in the proportion of patients who achieved a CD4/CD8 ratio > 1 (28.39 vs. 20.80, P = 0.145) (data not shown). As mentioned earlier, this analysis could not be carried out in the patients from the ANDES study, as its follow-up period was finalized at week 48.

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