What is the effect of antiretroviral therapy (ART) on patients with Human Immunodeficiency Virus (HIV)-immune complex kidney disease (HIVICK) and HIV-associated nephropathy?

ART 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, 2

Evidence for HIVAN

The evidence for ART benefit in HIVAN is robust and unequivocal:

• Patients with biopsy-confirmed HIVAN who received ART had significantly longer time to ESRD and higher overall renal survival compared to untreated patients. 1
• ART dramatically slowed the rate of GFR decline in HIVAN patients compared to those without treatment. 1
• The DHHS and International Antiviral Society guidelines recommend initiating ART immediately in patients with HIVAN, regardless of CD4 count. 1
• Multiple studies demonstrate that ART preserves kidney function in HIVAN patients, with substantial renal benefits associated with suppression of HIV-1 viral replication. 3
• A systematic review found that nine HIVAN studies showed decreased progression to ESKD or death for subjects treated with cART versus those untreated (though two studies showed no survival advantage). 2

Evidence for HIVICK

While the evidence base for HIVICK is smaller than for HIVAN, it still demonstrates clear benefit:

• A 2022 systematic review found that three HIVICK studies showed improvement in delaying ESKD in subjects on cART compared to untreated subjects, concluding that cART appeared to reduce the risk to ESKD or death in patients with both HIVAN and HIVICK. 2
• A 2016 multicentre study demonstrated that patients with HIVICK who initiated ART and achieved suppression of HIV RNA experienced improvements in estimated GFR and proteinuria, suggesting a pathogenic role for HIV replication in HIVICK development. 4
• The KDOQI commentary cites a small cohort demonstrating benefit in renal outcomes with antiretrovirals in HIVICK patients, though it notes uncertainty about HIV's direct role in HIVICK. 1

Guideline Evolution and Current Recommendations

• The IDSA and HIVMA guidelines acknowledge that it is not known whether ART prevents or modifies the course of other HIV-related kidney diseases, including HIVICK. 1 However, this represents older guidance that has been superseded by newer evidence.
• The KDIGO guidelines now recommend ART initiation in all patients with HIV and CKD, representing a broader recommendation than previous guidelines that focused only on HIVAN. 1
• The benefits of early ART initiation outweigh potential side effects, particularly given improved safety profiles of modern antiretroviral regimens. 1

Clinical Implications for Your Patient

For this 48-year-old woman with newly diagnosed HIV and biopsy-confirmed HIVICK:

• Initiate ART immediately, regardless of CD4 count. 1
• The evidence demonstrates that achieving viral suppression can improve both GFR and proteinuria in HIVICK patients. 4
• HIVICK is associated with lower rates of progression to ESKD compared with HIVAN, but ART still provides significant benefit. 4
• Black ethnicity and detectable HIV RNA are associated with HIVICK development, making viral suppression particularly important. 4