1. EACS, 16th European Aids Conference; October 25-27, 2017; Milan, Italy
Durability of first-line antiretroviral therapies in HIV-infected patients in Germany: 12-month results from the PROPHET study M. Bickel1, C. Hoffmann2, E. Wolf3, C. Wyen4, C. Spinner5, C. Koegl3, A. Baumgarten6, H. Jaeger7, T. Lutz8, N. Postel9, M. Mueller10, A. Plettenberg11, S. Esser12, R. Pauli13, S. Klauke1, S. Mauss14 and K. Schewe2 for the PROPHET study group of dagnae e. V. 1Infektiologikum Frankfurt, Frankfurt, Germany, 2ICH Studycenter, Hamburg, Germany, 3MUC Research, Munich, Germany, 4Private Practice Ebertplatz, Cologne, Germany, 5Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany, 6Medical Center for Infectiology Berlin, Berlin, Germany, 7MVZ Karlsplatz, HIV Research and Clinical Care Centre, Munich, Germany, 8Infektiologikum Frankfurt, Department Friedenstrasse, Frankfurt, Germany, 9prinzmed, Practice for infectious diseases, Munich, Germany, 10Practice Schwabstrasse 26, Stuttgart, Germany, 11ifi-Studien und Projekte GmbH an der Asklepios Klinik St. Georg, Haus L, Hamburg, Germany, 12University HIV/STD Center Essen, Department of Dermatology and Venerology, University Hospital Essen, Essen, Germany, 13Practice Isartor, Munich, Germany, 14MVZ Dusseldorf, Dusseldorf, Germany
The German Association of Physicians specialized in HIV Care
Nuernberger Str. 16
10789 Berlin
Background
Persistence
PROPHET is a nation-wide, 2-year, prospective, multi-center, observational cohort study in treatment-naïve HIV-infected patients initiated on antiretroviral therapy (ART). The primary objectives are to evaluate pharmacoeconomic and clinical outcomes of different first-line combination antiretroviral treatment strategies recommended by treatment guidelines.
Here we present the 12-month results on drug persistence and effectiveness.
At month 12, 424/444 (95%) of patients were still in follow-up. Any ART modification (change of NRTI backbone and/or 3rd agent) was observed in 29.7% of patients. Most common ART modifications involved a 3rd agent class change (see Table 2).
Table 2. ART modifications and study discontinuations during 12-month follow-up
Total
INI arm
NNRTI arm
PI arm
ART modification, yes, N (%)
132 (29.7)
27 (15.9)
35 (26.3)
70 (49.6)
Backbone change
38 (8.6)
15 (8.8)
10 (7.5)
13 (9.2)
3rd agent (within class)
6 (1.4)
3 (1.8)
1 (0.8)
2 (1.4)
Backbone and 3rd agent (within class)
2 (0.5)
2 (1.2)
0 (0.0)
3rd agent (class change)
86 (19.4)
7 (4.1)
24 (18.0)
55 (39.0)
Study discontinuations
20 (4.5)
6 (4.5)
7 (5.0)
Methods
Inclusion criteria
Adult, chronically HIV-infected, treatment-naïve patients initiated on two NRTIs (TDF/FTC or ABC/3TC) plus either an INI, a NNRTI or a boosted PI between 01 August 2014 and 30 September 2015.
Statistical methods
Drug persistence: Kaplan-Meier (KM) statistics were used for time-to-event analyses: Any ART modification was considered as event (switching from tenofovir disoproxil fumarate to tenofovir alafenamide included, e.g. Stribild to Genvoya or Evipera to Odefsey; multi (MTR) to single tablet regimen (STR) containing the same components excluded, e.g. switching from Tivicay and Kivexa to Triumeq). In all other cases (e.g. death, lost to follow-up) the time of the last follow-up was censored.
Effectiveness: HIV-RNA levels <50 (<200) copies/mL at month 12 irrespective of ART modification (missing=excluded)
For comparing median values across subgroups, the Kruskal-Wallis test was used, for comparing frequencies the χ² test.
The Kaplan-Meier estimates of patients still on initial cART after 12 months were 87%, 80% and 57% in the INI, NNRTI and PI arms, respectively (see Figure 1).
100%
75%
50%
25% 0%
Patients on initial regimen [%]
141
131
126
122
118
114
108
103 99 92 86 81 76
PI arm
133
130
128
123
119
115
113
110
109
104
101
NNRTI arm
170
165
162
159
158
156
152
148
147
144
143
INI arm
Numbers at risk 1 2 3 4 5 6 7 8 9 10 11 12
Months
57%
80%
87%
Results
Virologic failure was the reason for ART modification in only 1.8% of patients (n=8/444; INI: n=0, NNRTI: n=5, PI: n=3 with documented de novo development of resistance in 0, 3 and 0 patients, respectively).
The study population includes 444 eligible patients from 24 centers (INI arm: n=170, NNRTI arm: n=133, PI arm: n=141).
Baseline characteristics and antiretroviral combinations
Baseline characteristics and antiretroviral combination partners are shown in Table 1.
Most common initial antiretroviral combinations were tenofovir/emtricitabine plus either dolutegravir, rilpivirine, or darunavir.
Table 1. Baseline characteristics and initial antiretroviral combination partners
Total
INI arm
NNRTI arm
PI arm N
444
170
133
141
Age* [years]; Median (IQR)
40 ( )
41 ( )
37 ( )
39 ( )
Sex: male; N (%)
403 (90.8)
158 (92.9)
118 (88.7)
127 (90.1)
HIV-related characteristics
CDC stage C (AIDS)*, N (%)
45 (10.1)
17 (10.0)
2 (1.5)
26 (18.4)
CD4 cell count* [cells/µL], median (IQR)
374
(202 – 525)
383
(210 – 504)
435
(330 – 598)
265
(99 – 434)
HIV-1 RNA* [log copies/mL], median (IQR)
4.7 (4.2 – 5.2)
4.7 (4.3 – 5.2)
4.4 (4.0 – 4.7)
5.1 (4.6 – 5.4)
HIV-1 RNA > * [copies/mL], N (%)
141 (31.8)
55 (32.4)
8 (6.0)
78 (55.3)
Late presenters*, N (%)
(CD4<350/µL and/or AIDS)
204 (45.9)
71 (41.8)
41 (30.8)
92 (65.2)
Antiretroviral combinations partners
Backbone at baseline
TDF/FTC, N(%)
ABC/3TC, N (%)
346 (77.9)
98 (22.1%)
85 (50)
130 (97.7)
3 (2.3)
131 (92.9)
10 (7.1)
3rd agent at baseline
>10%, N (%)
----
dolutegravir (DTG):
142 (83.5)
rilpivirine (RPV):
126** (94.7)
darunavir (DRV):
Figure 1. Kaplan-Meier-analysis: Time on initial regimen
Virologic and immunologic effectiveness
HIV-RNA levels at month 12 were available in 406 patients. Irrespective of ART modification, viral suppression rates defined as HIV-RNA<50 (<200) copies/mL, were 92% (98%) in the INI arm, 98% (98%) in the NNRTI arm and 88% (95%) in the PI arm (see Figure 2).
Figure 2. Viral suppression rates at month 12 (missing values excluded)
92.9
4.2
92.4
5.1
98.4
88.1
7.1 10 20 30 40 50 60 70 80 90
100
Proportion of patients [%]
TOTAL
INI arm
NNRTI arm
PI arm N=
<50cp/mL
50-199cp/mL
IQR: interquartile range;
*P<0.05 (comparison across groups); **n=125 using single tablet regime RPV/TDF/FTC
Median change in CD4 cell counts was 222µL (Table 3).
Acknowledgement
Table 3. Change in CD4 cell count at month 12
We thank all participating patients as well as the staff and investigators of the study.
Financial support was provided by Janssen-Cilag.
Total
INI arm
NNRTI arm
PI arm
Change in CD4 cell count, cells/µL, median (IQR)
222 (111 – 336)
240 (131 – 366)
184 (60 – 294)
231 (140 – 350)
Participating centers and organizations
Practice Kreuzberg, H. Schulbin, Berlin; Medical Center for Infectiology Berlin, A. Baumgarten, C. Mayr, Berlin; MVZ Aerzteforum Seestrasse, W. Schmidt, Berlin; Department of Medicine I, Bonn University Hospital, J. Rockstroh, Bonn; Private Practice Ebertplatz, C. Wyen, E. Voigt, T. Kuemmerle, Cologne; Practice Hohenstaufenring, S. Scholten, S. Schneeweiss, Cologne; Department I of internal medicine, University Hospital of Cologne, G. Faetkenheuer, Cologne; Center for HIV and Hepatogastroenterology, S. Mauss, Duesseldorf; University HIV/STD Center Essen, Department of Dermatology and Venerology, Universitiy Hospital Essen, S. Esser, Essen; Infektiologikum Frankfurt, M. Bickel, S. Klauke, T. Lutz, S. Usadel, Frankfurt; Practice Dr. Ackermann, Halle; ifi-Studien und Projekte GmbH, an der Asklepios Klinik St. Georg, Haus L, A. Stoehr, A. Plettenberg, Hamburg; ICH Studycenter, C. Hoffmann, H.-J. Stellbrink, M. Sabranski, K. Schewe, Hamburg; Hannover Medical School, M. Stoll, Hannover; Center for Medical Studies, H. Heiken, Hannover; MVZ Karlsplatz, HIV Research and Clinical Care Centre, Munich, H. Jaeger, Munich; Practice Isartor, R. Pauli, W. Becker, Munich; University Hospital of Munich, J. Bogner, Munich; Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, C. Spinner, Munich; prinzmed, Practice for infectious diseases, N. Postel, Munich; Center for Interdisciplinary Medicine, S. Christensen, Muenster; Practice Schwabstrasse 26, M. Mueller, A. Ulmer, Stuttgart; Institute for Health Care Management and Research, J. Wasem, A. Neumann, Duisburg-Essen.
Conclusion
ART modification in PROPHET was frequent with 30 % after one year, most commonly for strategic reasons.
Despite a high rate of late presenters in this cohort study, modifications due to virologic failure were rare (<2%).
dagnae e.V. ▪ Nuernberger Str. 16 ▪ Berlin ▪ & MUC Research GmbH ▪ Karlsplatz 8 ▪ Munich ▪ Germany ▪