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  17th European AIDS Conference
November 6-9
2019, Basel
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Incidence of CKD with TDF and non-TDF containing antiretroviral regimens by baseline D:A:D CKD risk in people living with HIV (PLWH)
  Low Kidney Disease Risk Score Signals Continuing Low Risk Even With TDF
17th European AIDS Conference, November 6-9, 2019, Basel
Mark Mascolini
Chronic kidney disease (CKD) incidence (the new-diagnosis rate) proved low in a 9802-person US study of people starting their first antiretroviral regimen [1]. Among people who started treatment with a low D:A:D CKD risk score, CKD incidence was no higher with TDF than without TDF.
Large studies in Europe and the United States establish a link between TDF use and risk of kidney impairment. But recent work indicates that TDF-related kidney toxicity risk may increase in regimens using a boosting agent (ritonavir or cobicistat). Rates of kidney impairment appear to be similar with TDF in an unboosted regimen and with tenofovir alafenamide (TAF).
This analysis by OPERA cohort investigators aimed to weigh the risk of incident CKD according to the D:A:D CKD risk score among people starting treatment with or without TDF. Validated in European cohorts and in OPERA, the D:A:D CKD risk score determines whether a person has low, medium, or high risk based on variables including age, sex, estimated glomerular filtration rate (eGFR), injection drug use, and cardiovascular disease [2].
OPERA includes more than 100,000 people with HIV in 65 US cities and 1 US territory, or about 8% of all HIV-positive people in care in the United States. This analysis focused on antiretroviral-naive adults starting antiretroviral therapy (ART) by June 30, 2018 with at least one eGFR above 60 mL/min in the 12 months before beginning treatment. Everyone had 2 or more eGFR measures after starting ART. The researchers defined incident CKD at 2 or more consecutive eGFRs below 60 mL/min more than 90 days apart.
The study population included 6222 people starting a TDF regimen and 3580 starting a non-TDF combination. According to the D:A:D risk score, 76% in the TDF group and 79% in the non-TDF group had an initial low risk of CKD, 16% and 13% had a medium risk, and 8% and 8% had a high risk.
In the low-, medium-, and high-risk groups, median ages were 31, 48, and 52 among people starting TDF and 29, 49, and 52 in people starting a non-TDF regimen. Respective proportions of women were 12%, 18%, and 30% in the TDF group and 9%, 20%, and 29% in the non-TDF group. Blacks made up 42%, 34%, and 38% of the low-, medium-, and high-risk TDF group and 47%, 43%, and 52% of the respective non-TDF groups. The three TDF groups usually started ART in 2012-2013, compared with 2016-2017 for the non-TDF groups.
Compared with the low-CKD-risk non-TDF group, the medium- and high-risk TDF and non-TDF groups had significantly higher proportions (1) taking a kidney-toxic drug, (2) taking a drug minimizing proteinuria, (3) with HCV infection, and (4) with hypertension. Median follow-up stood at 29 months in people taking TDF and 19 months in the non-TDF group.
Logistic regression analysis to estimate risk of incident CKD by baseline CKD risk and TDF use adjusted for (1) baseline age, sex, race/ethnicity, calendar year, and boosting/anchor class, and (2) time-updated alcohol misuse, HIV viral load, medications (kidney-toxic, affecting proteinuria), HCV, diabetes, and hypertension. Compared with low baseline CKD risk and no TDF, people with low risk taking TDF had a statistically indistinguishable risk of new CKD (adjusted odds ratio [aOR] 0.55, 95% confidence interval [CI] 0.19 to 1.54).
Compared with the low baseline CKD risk and no-TDF group, people with an initial high CKD risk had an independently greater risk of incident CKD regardless of whether they took TDF (aOR 12.84, 95% CI 4.57 to 36.07) or did not take TDF (aOR 19.55, 95% CI 7.35 to 52.00). Among people with an initial medium CKD risk, odds of incident CKD proved somewhat higher with TDF (aOR 3.96, 95% CI 1.38 to 11.39) than without TDF (aOR 2.32, 95% CI 0.72 to 7.52).
Compared with people taking a nonboosted non-TDF regimen, adjusted risk of incident CKD was no greater with a boosted non-TDF regimen (aOR 1.28, 95% CI 0.70 to 2.33), a nonboosted TDF regimen (aOR 0.69, 95% CI 0.35 to 1.35), or a boosted TDF regimen (aOR 1.10, 95% CI 0.59 to 2.03). This lack of association did not change when the researchers further corrected the analysis for eGFR.
The OPERA investigators concluded that progression to CKD strongly reflects baseline CKD risk. They noted that people with a low initial D:A:D CKD risk score made up the biggest group of antiretroviral-naive people with HIV--and this group did not see their CKD risk increase if they started TDF. The researchers proposed that "TDF may remain a viable option for people living with HIV with low CKD risk" when they start ART.
1. Hsu R, Brunet L, Fusco J, et al. Incidence of CKD with TDF and non-TDF containing antiretroviral regimens by baseline D:A:D CKD risk in people living with HIV (PLWH). 17th European AIDS Conference, November 6-9, 2019, Basel. Abstract PS4/2.
2. Mocroft A, Lundgren JD, Ross M, et al. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study. PLoS Med. 2015;12:e1001809.