Antiretroviral Therapy Benefits Both HIVAN and HIVICK
The correct answer is D: ART has reduced the risk of end-stage kidney disease or death in people with both HIV-associated nephropathy and HIVICK. 1
Evidence for HIVAN
ART is definitively beneficial in HIVAN, with robust observational data demonstrating improved kidney outcomes:
Patients with biopsy-confirmed HIVAN who received ART had significantly longer time to ESRD (18.4 months vs 3.9 months) and higher overall renal survival (18.1% vs 12.5%) compared to untreated patients 2
ART dramatically slowed the rate of GFR decline in HIVAN patients (0.08 vs 4.3 mL/minute/month without treatment, P = 0.04) 2
In one retrospective series, zero of 5 HIVAN patients on ART experienced serum creatinine doubling, while all 6 untreated patients progressed to ESRD 2
HIVAN is now recognized as a specific indication to initiate ART immediately, regardless of CD4 count, by DHHS and International Antiviral Society guidelines 2
Evidence for HIVICK
While the evidence base is smaller than for HIVAN, emerging data supports ART benefit in HIVICK:
A 2022 systematic review analyzing 11 studies found that three HIVICK studies demonstrated improvement in delaying ESKD in subjects on ART compared to untreated subjects 1
A 2016 multicentre study of 65 HIVICK patients showed that those who initiated ART and achieved HIV RNA suppression experienced improvements in estimated glomerular filtration rate and proteinuria 3
Black ethnicity and detectable HIV RNA were associated with HIVICK development, suggesting a pathogenic role for HIV replication that ART can address 3
HIVICK patients had lower rates of progression to ESRD compared to HIVAN and IgA nephropathy, and ART appeared to improve kidney function particularly in those with detectable HIV RNA at diagnosis 3
Important Caveats
The 2014 IDSA/HIVMA guidelines explicitly state: "It is not known whether ART prevents or modifies the course of other HIV-related kidney diseases, including HIV immune complex kidney disease." 2 This reflects the limited evidence available at that time.
However, the 2023 KDOQI commentary acknowledges this uncertainty while noting: "Uncertainty remains about HIV's direct role in HIVICK and the role of antiretrovirals in improving kidney outcomes in those patients," but cites a small cohort (n=16) demonstrating benefit in renal outcomes with antiretrovirals in HIVICK patients, though not statistically significant 2
The most recent and highest quality evidence—the 2022 systematic review—provides the strongest support for option D, concluding that "cART appeared to reduce the risk to ESKD or death in patients with both HIVAN and HIVICK." 1
Clinical Recommendation
For this 48-year-old woman with biopsy-proven HIVICK, initiate ART immediately regardless of CD4 count, adjusted for her degree of kidney impairment. 2 The 2023 KDIGO guidelines recommend ART initiation in all patients with HIV and CKD, representing a broader recommendation than the previous 2015 guideline that focused only on HIVAN 2
The benefits of early ART initiation outweigh potential side effects, particularly given improved safety profiles of modern antiretroviral regimens 2