Open Access Research article

Long-term CD4+ T-cell count evolution after switching from regimens including HIV nucleoside reverse transcriptase inhibitors (NRTI) plus protease inhibitors to regimens containing NRTI plus non-NRTI or only NRTI

Carlo Torti1*, Antonella d'Arminio-Monforte2, Anton L Pozniak3, Giuseppe Lapadula4, Giuliana Cologni5, Andrea Antinori6, Andrea De Luca7, Cristina Mussini8, Antonella Castagna9, Paola Cicconi2, Lorenzo Minoli10, Andrea Costantini11, Giampiero Carosi1, Hua Liang12, Bruno M Cesana13 and the MASTER, Chelsea & Westminster, ICONA, Modena and S. Raffaele HIV Cohorts

Author Affiliations

1 University of Brescia, Italy

2 S. Paolo Hospital, Milano, Italy

3 Chelsea & Westminster Hospital, London, UK

4 "S. Gerardo" Hospital, Monza, Italy

5 Ospedali Riuniti, Bergamo, Italy

6 INMI "L. Spallanzani" IRCCS, Rome, Italy

7 Sacro Cuore Catholic University, Rome, Italy

8 University of Modena and Reggio Emilia, Italy

9 Vita-Salute University, Milan, Italy

10 IRCCS Policlinico S. Matteo, Pavia, Italy

11 University of Ancona, Italy

12 Department of Biostatics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA

13 Chair of Statistics, University of Brescia, Italy

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BMC Infectious Diseases 2011, 11:23  doi:10.1186/1471-2334-11-23

Published: 25 January 2011



Data regarding CD4+ recovery after switching from protease inhibitor (PI)-based regimens to regimens not containing PI are scarce.


Subjects with virological success on first-PI-regimens who switched to NNRTI therapy (NNRTI group) or to nucleoside reverse transcriptase (NRTI)-only (NRTI group) were studied. The effect of the switch on the ongoing CD4+ trend was assessed by two-phase linear regression (TPLR), allowing us to evaluate whether a change in the CD4+ trend (hinge) occurred and the time of its occurrence. Furthermore, we described the evolution of the frequencies in CD4-count classes across four relevant time-points (baseline, before and immediately after the switch, and last visit). Finally, we explored whether the CD4+ counts evolved differently in patients who switched to NNRTI or NRTI-only regimens by considering: the overall CD4+ trends, the time to CD4+≥ 500/mm3 after the switch, and the area-under-the-curve (AUC) of the CD4+ after the switch.


Eight hundred and ninety-six patients, followed for a median of 2,121 days, were included. At TPLR, hinges occurred in 581/844 (68.9%), but in only 40/581 (6.9%) within a time interval (180 days) compatible with a possible relationship to the switch; furthermore, in 19/40 cases, CD4+ counts appeared to decrease after the hinges. In comparison with the NNRTI group, the NRTI group showed CD4+ count greater at baseline (P = 0.0234) and before the switch (P ≤ 0.0001), superior CD4+ T-cell increases after HAART was started, lower probability of not achieving CD4+ ≥ 500/mm3 (P = 0.0024), and, finally, no significant differences in the CD4+ T-cell AUC after the switch after adjusting for possible confounders (propensity score and pre-switch AUC). Persistence at CD4+ < 200/mm3 was observed in 34/435 (7.5%) patients, and a decrease below this level was found in only 10/259 (3.9%) with baseline CD4+ ≥ 350/mm3.


Switching from first-line PI to NNRTI- or NRTI-based regimens did not seem to impair CD4+ trend over long-term follow-up. Although the greater CD4+ increases in patients who switched to the NRTI-only regimen was due to higher CD4+ counts before the switch, several statistical analyses consistently showed that switching to this regimen did not damage the ongoing immune-reconstitution. Lastly, the observation that CD4+ T-cell counts remained low or decreased in the long term despite virological success merits further investigation.