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Similar virologic response after initiation of triple-class antiretroviral therapy in primary and chronic HIV infection

2012; Lippincott Williams & Wilkins; Volume: 26; Issue: 15 Linguagem: Inglês

10.1097/qad.0b013e3283580515

1473-5571

Marlous L. Grijsen, Rebecca Holman, Ferdinand W.N.M. Wit, Luuk Gras, Selwyn H. Lowe, Kees Brinkman, Frank de Wolf, Jan M. Prins,

HIV/AIDS Research and Interventions

Studies comparing the virologic response to combination antiretroviral therapy (cART) between persons with primary HIV infection (PHI) and chronic HIV infection (CHI) have shown inconsistent results [1–5]. In a recent issue of this journal, a more rapid plasma viral load (pVL) decline was observed in PHI as compared to CHI after initiation of a standard non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen [1]. We compared the time to viral suppression in our cohort of 70 PHI-patients treated with triple-class therapy with that of 80 naive CHI patients with comparable treatment and initial pVL. PHI-patients were selected from the Primo-SHM cohort, a prospective cohort study in the Netherlands with an embedded randomized trial, which investigated the effects of 24 or 60 weeks of cART during PHI [6]. PHI was defined as a negative or indeterminate Western blot combined with a detectable pVL, or, in case of a positive Western blot, a negative HIV-screening test result 180 days or less. CHI patients were selected from the Dutch observational HIV cohort (ATHENA) [7]. Inclusion criteria for PHI and CHI patients in the present study were: age at least 18 years, treatment-naive, a pVL of at least 100 000 copies/ml, and start of triple-class cART between January 2002 and June 2010. Time to viral suppression, defined as a pVL less than 50 copies/ml, was compared between the two cohorts using Kaplan–Meier plots and multivariate Cox regression analysis, with the last adjusted for the pVL before treatment and regimens containing an integrase inhibitor. Analyses were intention-to-treat, regardless of treatment changes. Patients were censored when lost to follow-up or when cART was interrupted for more than 2 weeks. χ2, Fisher's exact and Kruskal–Wallis tests were used where appropriate. Sixty-four of 70 PHI patients (91%) and 72 of 80 CHI patients (90%) were men (P = 0.8). The PHI patients were younger [median age 38 (interquartile range, IQR 31–45) versus 42 (IQR 36–49) years; P = 0.02], were more often MSM [59 (84%) versus 50 (63%); P = 0.003], and had a higher median CD4 cell count prior to treatment than CHI patients [470 (IQR 300–550) versus 97 (39–215) cells/μl; P < 0.001]. Median baseline pVL was similar in both groups: 5.7 (IQR 5.3–6.1) versus 5.7 (5.4–6.1) log10 copies/ml (P = 0.4). Fifty-seven PHI patients (81%) had a negative or indeterminate Western blot, 67 (96%) were symptomatic during PHI, and the median time between HIV diagnosis and start of early cART was 4 (IQR 3–7) weeks. Twenty-nine CHI patients (36%) had experienced a CDC-C event before treatment initiation. All 70 PHI patients and 69 of 80 CHI patients (86%) initiated a triple-class regimen containing two NRTIs, an NNRTI and a boosted protease inhibitor (PI). The remaining 11 CHI patients (14%) received an integrase inhibitor in addition to two NRTIs and an NNRTI (n = 5), or boosted PI (n = 6). HIV genotyping was available for 111 patients (74%): three of 54 PHI (6%) and six of 57 CHI patients (11%; P = 0.5) harboured one or more transmitted drug resistance mutations in reverse transcriptase or protease [8], of whom one PHI patient and two CHI patients were judged as being treated with an ineffective triple-class regimen and, therefore, excluded from further analyses. A total of 47 of 69 PHI patients (68%) and 59 of 78 CHI patients (76%) switched to an alternative or simplified regimen before 24 weeks (P = 0.3). Median time to viral suppression was comparable between both groups (log-rank, P = 0.5; Fig. 1). This was confirmed by the adjusted Cox regression analysis [hazard ratio PHI versus CHI 1.08 (95% confidence interval, 0.74–1.58), P = 0.7]. After 24 weeks 50% of the patients in both groups had a pVL 50 copies/ml or less, and after 48 weeks this was 82% in PHI and 93% in CHI patients.Fig. 1: Kaplan–Meier curve of the probability to achieve viral suppression [plasma viral load (pVL) 100.000 copies/ml) initiating triple-class therapy.The time to viral suppression in PHI was comparable to CHI after initiation of triple-class therapy. This is in contrast with a recent report, in which phase II viral decay was faster in PHI than in CHI, which resulted in a shorter time to viral suppression after start of treatment with dual-class, NNRTI-based therapy [1]. A much smaller study, which was designed to assess the effect of raltegravir on viral dynamics, also demonstrated a faster time to viral suppression in PHI than in CHI, but did not adjust for the higher baseline pVL in the CHI patients [2]. In contrast to our study, both latter studies compared patients receiving standard triple therapy [1,2], and the question is whether this explains why these two studies found a difference between PHI and CHI patients. A prospective cohort study observed that PHI patients receiving quadruple dual-class therapy had a faster phase II viral decay and a nonsignificant shorter time to viral suppression than PHI patients on triple therapy [9]. However, it is not clear how this differential effect of the regimen on HIV suppression should explain a shorter time to viral suppression in PHI versus CHI patients for dual-class [1], as opposed to triple-class therapy. In summary, our results demonstrate that PHI and CHI patients with high viremia are equally rapidly suppressed after initiation of triple-class therapy, suggesting that the virologic response to cART is not related to the stage of HIV infection. Acknowledgements The ATHENA national observational cohort has been made possible through the collaborative efforts of the following physicians (*site coordinating physicians): Academisch Medisch Centrum, University of Amsterdam, Amsterdam: Professor Dr J.M. Prins*, Professor Dr T.W. Kuijpers, Dr H.J. Scherpbier, Dr K. Boer, Dr J.T.M. van der Meer, Dr F.W.M.N. Wit, Dr M.H. Godfried, Professor Dr P. Reiss, Professor Dr T. van der Poll, Dr F.J.B. Nellen, Professor Dr J.M.A. Lange, Dr S.E. Geerlings, Dr M. van Vugt, Drs D. Pajkrt, Drs J.C. Bos, Drs M. van der Valk, Drs M.L. Grijsen, Dr W.J. Wiersinga. Maastricht University Medical Center, Maastricht: Dr G. Schreij, Dr S.H. Lowe*, Dr A. Oude Lashof, Dr D. Posthouwer. Catharina-ziekenhuis, Eindhoven: Drs M.J.H. Pronk*, Dr B. Bravenboer. Erasmus Medisch Centrum, Rotterdam: Dr M.E. van der Ende*, Drs T.E.M.S. de Vries-Sluijs, Dr C.A.M. Schurink, Drs M. van der Feltz, Dr J.L. Nouwen, Dr L.B.S. Gelinck, Dr A. Verbon, Drs B.J.A. Rijnders, Dr L. Slobbe, Dr E.C.M. van Gorp. Flevoziekenhuis. Almere: Dr J. Branger*. HagaZiekenhuis, Den Haag: Dr E.F. Schippers*, Dr C. van Nieuwkoop. Isala Klinieken, Zwolle: Dr P.H.P. Groeneveld*, Dr M.A. Alleman, Drs J.W. Bouwhuis. Kennemer Gasthuis: Professor Dr R.W. ten Kate*, Dr R. Soetekouw. Leids Universitair Medisch Centrum, Leiden: Dr F.P. Kroon*, Professor Dr P.J. van den Broek, Professor Dr J.T. van Dissel, Dr S.M. Arend, Drs C. van Nieuwkoop, Drs M.G.J. de Boer, Drs H. Jolink. Maasstadziekenhuis, Rotterdam: Dr J.G. den Hollander*, Dr K. Pogany. Medisch Centrum Alkmaar, Alkmaar: Drs G. van Twillert*, Drs W. Kortmann*. Medisch Centrum Haaglanden, Den Haag: Dr R. Vriesendorp*, Dr E.M.S. Leyten, Dr L.B.S. Geelink. Medisch Spectrum Twente, Enschede: Dr C.H.H. ten Napel*, Drs G.J. Kootstra. Onze Lieve Vrouwe Gasthuis, Amsterdam: Professor Dr K. Brinkman*, Dr W.L. Blok, Dr P.H.J. Frissen, Drs W.E.M. Schouten, Drs G.E.L. van den Berk. Sint Elisabeth Ziekenhuis, Tilburg: Dr J.R. Juttmann*, Dr M.E.E. van Kasteren, Drs A.E. Brouwer. Sint Lucas Andreas Ziekenhuis, Amsterdam: Dr J. Veenstra*, Dr K.D. Lettinga. Slotervaartziekenhuis, Amsterdam: Dr J.W. Mulder*, Drs P.M. Smit, Drs S.M.E. Vrouenraets, Dr F.N. Lauw. Stichting Medisch Centrum Jan van Goyen, Amsterdam: Drs A. van Eeden*, Dr D.W.M. Verhagen*. Universitair Medisch Centrum Groningen, Groningen: Drs H.G. Sprenger*, Drs R. Doedens, Dr E.H. Scholvinck, Drs S. van Assen, Dr W.F.W. Bierman. Universitair Medisch Centrum Sint Radboud, Nijmegen: Dr P.P. Koopmans*, Professor Dr R. de Groot, Dr M. Keuter, Dr A.J.A.M. van der Ven, Dr H.J.M. ter Hofstede, Dr M. van der Flier, Drs A.M. Brouwer, Dr A.S.M. Dofferhoff. Universitair Medisch Centrum Utrecht, Utrecht: Professor Dr A.I.M. Hoepelman*, Dr T. Mudrikova, Dr M.M.E. Schneider, Drs C.A.J.J. Jaspers,, Dr P.M. Ellerbroek, Dr J.J. Oosterheert, Dr J.E. Arends, Dr M.W.M. Wassenberg, Dr R.E. Barth. Vrije Universiteit Amsterdam, Amsterdam: Dr M.A. van Agtmael*, Drs J. de Vocht, Dr R.M. Perenboom, Drs F.A.P. Claessen, Drs E.A. bij de Vaate. Ziekenhuis Rijnstate, Arnhem: Dr C. Richter*, Dr J.P. van der Berg, Dr E.H. Gisolf. Admiraal De Ruyter Ziekenhuis, Vlissingen: Drs M. van den Berge*, Drs A. Stegeman. Medisch Centrum Leeuwarden, Leeuwarden: Dr M.G.A. van Vonderen*, Drs D.P.F. van Houte. M.L.G. and J.M.P. conceived the study. R.H., L.G. and F.W.N.M.W. conducted the statistical analysis. M.L.G. and J.M.P. provided valuable input into interpretation of data. M.L.G. drafted the manuscript and J.M.P. critically revised the manuscript. All authors reviewed and approved the final version of the manuscript. Conflicts of interest Competing interests and financial support: none. There are no conflicts of interest.