Background

Antiretroviral therapy (ART) durability, time to modification or cessation, has declined. The study objective was to determine whether kidney dysfunction is contributing to reduced durability.

Methods

This retrospective follow-up study of CNICS evaluated treatment-naive PLWH initiating ART between 2007 and 2014. Regimen modification was defined as cessation/modification of any part of the 3-drug ART regimen. We evaluated the role of kidney dysfunction in initial regimen modification as both a mediator and effect measure modifier. Associations of the variables with the ART modification were examined using univariable and multivariable Cox proportional hazard models.

Results

Of 4515 PLWH included in the analysis, 1967 modified their ART. Of those receiving TDF-based ART (n = 3888), 1580 (41%) modified their regimen compared with 387 (62%) receiving other regimens. Overall, the median eGFR decreased by 5 mL/min/1.73 m (quartiles: first = -16, third = 0) from baseline to follow-up. Of the 128 patients with low baseline eGFR (<60 mL/min/1.73 m), the final eGFR remained low in 73% while it increased to above 60 mL/min/1.73 m in 27%. Of the 4387 with normal baseline eGFR, only 135 (3%) had a final eGFR <60 mL/min/1.73 m. Those with low eGFR at the baseline and/or final visits were more likely to modify ART than others (hazards ratio = 1.75, 95% confidence interval: 1.39 to 2.19, P < 0.001). Relative to other regimens, TDF-based ART was less likely to be modified when accounting for numerous clinical and demographic traits.

Conclusions

For patients in our study initiated on ART, including TDF-based ART, in the last decade, kidney dysfunction is not a major factor leading to regimen modification.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Proteinuria is associated with adverse clinical outcomes in HIV infection. Here we evaluated whether APOL1 risk alleles, previously associated with advanced kidney disease, are independently associated with proteinuria in HIV infection in a cross-sectional study of HIV-infected women in the Women's Interagency HIV Study. We estimated the percent difference in urine protein excretion and odds of proteinuria (≥200 mg/g) associated with two versus one or no APOL1 risk allele using linear and logistic regression, respectively. Of 1285 women successfully genotyped, 379 carried one and 80 carried two risk alleles. Proteinuria was present in 124 women, 78 of whom had proteinuria confirmed on a second sample. In women without prior AIDS, two risk alleles were independently associated with a 69% higher urine protein excretion (95% confidence interval (CI): 36, 108) and five-fold higher odds of proteinuria (95% CI: 2.45, 10.37) as compared with one or no risk allele. No association was found in women with prior AIDS. Analyses in which women with impaired kidney function were excluded and proteinuria was confirmed by a second urine sample yielded similar estimates. Thus, APOL1 risk alleles are associated with significant proteinuria in HIV-infected persons without prior clinical AIDS, independent of clinical factors traditionally associated with proteinuria. Trials are needed to determine whether APOL1 genotyping identifies individuals who could benefit from earlier intervention to prevent overt renal disease.

HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals.