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/mm3). 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.

HIV, drugs and the kidney.

Human immunodeficiency virus (HIV) affects over 36 million people worldwide. Antiretroviral therapy (ART) is expanding and improving HIV viral suppression, resulting in increasing exposure to drugs and drug interactions. Polypharmacy is a common complication as people are living longer on ART, increasing the risk of drug toxicities. Polypharmacy is related not only to ART exposure and medication for opportunistic infections, but also to treatment of chronic lifestyle diseases. Acute kidney injury (AKI) is frequent in HIV and is commonly the result of sepsis, dehydration and drug toxicities. Furthermore, HIV itself increases the risk of chronic kidney disease (CKD). Drug treatment is often complicated in people living with HIV because of a greater incidence of AKI and/or CKD compared to the HIV-negative population. Impaired renal function affects drug interactions, drug toxicities and importantly drug dosing, requiring dose adjustment. This review discusses ART and its nephrotoxic effects, including drug-drug interactions. It aims to guide the clinician on dose adjustment in the setting of renal impairment and dialysis, for the commonly used drugs in patients with HIV.