742
Greater Renal Function Preservation Is Associated with Continuous vs Intermittent ART
D Beversluis1, S Reynolds2, C Kityo3, R Salata1, M Dybul4, P Mugyenyi3, R Davey5, D AtwIIne3, T Quinn2, and Robert Kalayjian*1
1Case Western Reserve Univ Sch of Med, Cleveland, OH, US; 2Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 3Joint Clinical Res Ctr, Kampala, Uganda; 4UNAIDS, Geneva, Switzerland; and 5NIAID, NIH, Bethesda, MD, US
Background: ART improves
renal function in association with viral suppression, and possibly by other
mechanisms. Intermittent ART is a strategy to minimize the cost and the
toxicity of ART. We compared renal function in persons who enrolled in a
randomized, controlled trial of short-cycle, structured, intermittent vs
continuous ART in Kampala, Uganda.
Methods: HIV-1-infected
adults who were receiving ART and with serum creatinine <2.0 mg/dL, CD4
cells >125/mL, and plasma HIV RNA
<500 copies/mL longer than 3 months prior to screening, were randomized to
receive: 7 days on/7 days off ART (Arm 1); 5 days on/2 days off ART (Arm 2);
or continuous ART (Arm 3). Glomerular filtration rate (GFR) was estimated by
modified MDRD from serum creatinine levels collected over 80 weeks. GFR slopes
were compared between the arms using mixed effects linear models, adjusted for
time-varying CD4 cells and HIV RNA.
Results: Baseline
characteristics of the 151 subjects who enrolled were not significantly
different between the arms. Randomization to Arm 1 was prematurely discontinued
after 1 year. Despite comparable follow-up durations though, Arm 1 subjects had
a significantly greater rate of GFR decline than the other 2 arms (p = 0.008
for global differences between the arms), which was evident despite an
independent, negative contribution to GFR slope by HIV RNA (10.3 mL/min*1.73
m2*year for each 1.0 log10 increase in HIV RNA, p =
0.047). GFR slopes were comparable between Arms 2 and 3.
|
|
Arm 1
7 days on/7 days off
|
Arm 2
7 days on/2 days off
|
Arm 3
continuous
|
|
Baseline Median Values
|
|
|
|
|
n
|
32
|
59
|
60
|
|
Age (years)
|
38
|
38
|
39
|
|
Sex (% female)
|
61.0
|
62.5
|
61.7
|
|
Body mass index
|
25.0
|
25.4
|
24.7
|
|
CD4 (cells/mL)
|
254
|
238
|
274
|
|
Log10
HIV RNA (copies/mL)
|
1.69
|
1.69
|
1.69
|
|
GFR (mL/min*1.73 m2)
|
115
|
130
|
117
|
|
Repeated Measures Analysis
|
|
|
|
|
GFR slope (mL/min*1.73 m2*year
)
(95%CI)
|
–22.2
(–32.4 to –12.1)
|
–7.5
(–14.2 to –0.9)
|
0.2
(–9.9 to 10.3)
|
Conclusion: Continuous,
compared to intermittent (7 days on/7days off) ART was associated with greater
GFR preservation, independent of the negative contributions by viral
replication to renal function, implying that other mechanisms in addition to
viral suppression may contribute to the renal benefits of ART.
|
