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BMC Medicine
Published in: BMC Medicine 1/2018

Open Access 01-12-2018 | Research article

Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: an observational cohort study

Authors: Cristina Mussini, Patrizia Lorenzini, Alessandro Cozzi-Lepri, Giulia Marchetti, Stefano Rusconi, Andrea Gori, Silvia Nozza, Miriam Lichtner, Andrea Antinori, Andrea Cossarizza, Antonella d’Arminio Monforte, for the Icona Foundation Study Group

Published in: BMC Medicine | Issue 1/2018

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Abstract

Background

The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART).

Methods

We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono).

Results

A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was −0.03 (95% confidence interval (CI) –0.05, –0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = −25.7) and those to dual regimen (ratio = −0.029, CD8 = +110.4).

Conclusions

We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained.
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Literature
1.
2.
3.
Arribas JR, Clumeck N, Nelson M, Hill A, van Delft Y, Moecklinghoff C. The MONET trial: week 144 analysis of the efficacy of darunavir/ritonavir (DRV/r) monotherapy versus DRV/r plus two nucleoside reverse transcriptase inhibitors, for patients with viral load <50 HIV-1 RNA copies/mL at baseline. HIV Med. 2012;13:398–405.CrossRefPubMed
4.
Valantin MA, Lambert-Niclot S, Flandre P, et al. Long-term efficacy of darunavir/ritonavir monotherapy in patients with HIV-1 viral suppression: week 96 results from the MONOI ANRS 136 study. J Antimicrob Chemother. 2012;67:691–5.CrossRefPubMed
5.
Raffi F, Babiker AG, Richert L, et al. Ritonavir-boosted darunavir combined with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority trial. Lancet. 2014;384:1942–51.CrossRefPubMed
6.
Perez-Molina JA, Rubio R, Rivero A, et al. Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015;15:775–84.CrossRefPubMed
7.
Di Giambenedetto S, Fabbiani M, Quiros Roldan E, et al. Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M). J Antimicrob Chemother. 2017;72:1163–71.PubMed
8.
9.
Cahn P, Andrade-Villanueva J, Arribas JR, et al. Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial. Lancet Infect Dis. 2014;14:572–80.CrossRefPubMed
10.
Cahn P, Rolòn MJ, Figueroa MI, Gun A, Paerson P, Sued O. Dolutegravir-lamivudine as initial therapy in HIV-infected, ARV naive patients: 48 week results of the PADDLE study. J Int AIDS Soc. 2017;20:21678.CrossRefPubMedPubMedCentral
11.
12.
Restelli U, Fabbiani M, Di Giambenedetto S, Nappi C, Croce D. Budget impact analysis of the simplification to atazanavir + ritonavir + lamivudine dual therapy of HIV-positive patients receiving atazanavir-based triple therapies in Italy starting from data of the Atlas-M trial. Clinicoecon Outcomes Res. 2017;9:173–9.CrossRefPubMedPubMedCentral
13.
Oddershede L, Walker S, Stöhr W, Dunn DT, Arenas-Pinto A, Paton NI, Sculpher M. Protease Inhibitor monotherapy Versus Ongoing Triple therapy (PIVOT) Trial Team. Cost effectiveness of protease inhibitor monotherapy versus standard triple therapy in the long-term management of HIV patients: analysis using evidence from the PIVOT trial. PharmacoEconomics. 2016;34:795–804.CrossRefPubMed
14.
Smith CJ, Ryom L, Weber R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384:241–8.CrossRefPubMed
15.
Trickey A, May MT, Schommers P, et al. CD4:CD8 ratio and CD8 count as prognostic markers for mortality in human immunodeficiency virus-infected patients on antiretroviral therapy: the Antiretroviral Therapy Cohort Collaboration (ART-CC). Clin Infect Dis. 2017;65:959–66.CrossRefPubMedPubMedCentral
16.
Mussini C, Lorenzini P, Cozzi-Lepri A, et al. CD4/CD8 ratio normalization and non-AIDS related events in individuals with HIV who achieved viral load suppression on antiretroviral therapy: an observational cohort study. Lancet HIV. 2015;2:e98–106.CrossRefPubMed
17.
Serrano-Villar S, Saiz T, Sulggi AL, et al. HIV infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+T cell activation and increased risk of non-AIDS morbidity and mortality. PLoS Pathog. 2014;10:e1004078.CrossRefPubMedPubMedCentral
18.
Hema MN, Ferry T, Dupon M, et al. Low CD4/CD8 ratio is associated with non-AIDS-defining cancers in patients on antiretroviral therapy: ANRS CO8(Aproco/copilote) prospective cohort study. PLoS One. 2016;11:e0161594.CrossRefPubMedPubMedCentral
19.
Triplette M, Attia EF, Akgun KM, et al. A low peripheral blood CD4/CD8 ratio is associated with pulmonary emphysema in HIV. PLoS One. 2017;12:e0170857.CrossRefPubMedPubMedCentral
20.
d'Arminio Monforte A, Cozzi-Lepri A, Rezza G, et al. Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naive Patients. AIDS. 2000;14:499–507.CrossRefPubMed
21.
Rusconi S, Vitiello P, Adorni F, et al. Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial. PLoS One. 2013;8:e80157.CrossRefPubMedPubMedCentral
22.
Helleberg M, Kronborg G, Ullum H, Ryder LP, Obel N, Gerstoft J. Course and clinical significance of CD8+T-cell counts in a large cohort of HIV-infected individuals. J Infect Dis. 2015;211:1726–34.CrossRefPubMed
23.
Writing committee of the CD4/CD8 Ratio Working Group of the French Hospital Database on HIV (FHDH-ANRS CO4). CD4/CD8 ratio restoration in long-term treated HIV-1-infected individuals: incidence and determinants. AIDS. 2017;31:1685–95.CrossRef
24.
Caby F, Guihot A, Lambert-Niclot S, et al. Determinants of a low CD4/CD8 ratio in HIV-1-infected individuals despite long-term viral suppression. Clin Infect Dis. 2016;62:1297–303.CrossRefPubMed
25.
Saracino A, Bruno G, Scudeller L, et al. Chronic inflammation in a long-term cohort of HIV-infected patients according to the normalization of the CD4:CD8 ratio. AIDS Res Hum Retrovir. 2014;30:1178–84.CrossRefPubMed
26.
Lambert-Niclot S, Flandre P, Valantin MA, et al. Similar evolution of cellular HIV-1 DNA level in darunavir/ritonavir monotherapy versus triple therapy in MONOI-ANRS136 trial over 96 weeks. PLoS One. 2012;7:e41390.CrossRefPubMedPubMedCentral
27.
Lombardi F, Belmonti S, Quiros-Roldan E, et al. Evolution of blood-associated HIV-1 DNA levels after 48 weeks of switching to atazanavir/ritonavir+lamivudine dual therapy versus continuing triple therapy in the randomized AtLaS-M trial. J Antimicrob Chemother. 2017;72:2055–9.CrossRefPubMed
28.
Gibellini L, Pecorini S, De Biasi S, et al. HIV-DNA content in different CD4+ T-cell subsets correlates with CD4+ cell : CD8+ cell ratio or length of efficient treatment. AIDS. 2017;31:1387–92.CrossRefPubMed
29.
Chereau F, Madec Y, Sabin C, et al. Impact of CD4 and CD8 dynamics and viral rebound on loss of virological control in HIV controllers. PLoS One. 2017;12:e0173893.CrossRefPubMedPubMedCentral
30.
Gianotti N, Marchetti G, Antinori A, et al. Brief report: drop in CD4+ counts below 200 cells/μL after reaching (or starting from) values higher than 350 cells/μL in HIV-infected patients with virological suppression. J Acquir Immune Defic Syndr. 2017;76:417–22.CrossRefPubMed
Metadata
Title
Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: an observational cohort study
Authors
Cristina Mussini
Patrizia Lorenzini
Alessandro Cozzi-Lepri
Giulia Marchetti
Stefano Rusconi
Andrea Gori
Silvia Nozza
Miriam Lichtner
Andrea Antinori
Andrea Cossarizza
Antonella d’Arminio Monforte
for the Icona Foundation Study Group
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2018
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-018-1046-2

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