The Evolving Spectrum of Kidney Histology in HIV-Positive Patients in South Africa

INTRODUCTION: Sub-Saharan Africa remains challenged by the highest burden of human immunodeficiency virus (HIV), an epidemic of tuberculosis (TB), and increasing number of people with HIV (PWH) on antiretroviral therapy (ART), all of which may result in kidney injury. METHODS: This observational cohort study describes the spectrum of kidney disease in PWH in South Africa, between 2005 and 2020. Kidney biopsies were analyzed in 4 time periods as follows: early ART rollout (2005–2009), tenofovir disoproxil (TDF) introduction (2010–2012), TDF-based fixed dose combination (2013–2015), and ART at HIV diagnosis (2016–2020). Logistic regression was used to identify factors associated with HIV-associated nephropathy or focal segmental glomerulosclerosis (HIVAN/FSGS) and tubulointerstitial disease (TID). RESULTS: We included 671 participants (median age 36, interquartile range, 21–44 years; 49% female; median CD4 cell count 162 [interquartile range, 63–345] cells/mm(3)). Over time, ART (31%–65%, P < 0.001), rate of HIV suppression (20%–43%, P < 0.001), nonelective biopsies (53%–72%, P < 0.001), and creatinine at biopsy (242–449 μmol/l, P < 0.001) increased. A decrease in HIVAN (45%–29% P < 0.001) was accompanied by an increase in TID (13%–33%, P < 0.001). Granulomatous interstitial nephritis accounted for 48% of TID, mostly because of TB. Exposure to TDF was strongly associated with TID (adjusted odds ratio 2.99, 95% confidence interval 1.89–4.73 P < 0.001). CONCLUSION: As ART programs intensified and increasingly used TDF, the spectrum of kidney histology in PWH evolved from a predominance of HIVAN in the early ART era to TID in recent times. The increase in TID is likely due to multiple exposures that include TB, sepsis, and TDF as well as other insults.