Spontaneous resolution of HIV-associated nephropathy in an elite controller
Blankson, Joel Na; Basseth, Christie Ra; Kuperman, Michaelb; Fine, Derek Ma
aDepartment of Medicine, USA
bDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Received 3 February, 2011
Accepted 8 February, 2011
Correspondence to Joel Blankson, Johns Hopkins School of Medicine, 831 Broadway Research Bldg, Baltimore, MD 21205, USA. Tel: +1 410 955 7757; fax: +1 410 502 1144; e-mail: email@example.com
HIV-1-associated nephropathy (HIVAN) is a progressive disease characterized by collapsing focal segmental glomerulosclerosis (FSGS) and proteinuria . It is usually associated with advanced HIV-1 disease, but it has been reported in primary HIV-1 infection . Although treatment with highly active antiretroviral therapy (HAART) has been shown to slow the progression of HIVAN , there has never been a reported case of spontaneous resolution of this disease.
Elite suppressors or controllers are HIV-1-infected individuals who control viral replication to below the limit of detection of commercial assays without antiretroviral therapy [4–6]. Here, we describe a patient who developed HIVAN during primary infection when he was transiently viremic. His renal function improved as viral replication was spontaneously controlled by his immune system.
The patient was a 23-year-old man with sickle cell disease who was admitted to the hospital with a 4-week history of fevers and acute renal failure with a creatinine of 2.7 mg/dl and 3+ protein seen on a urinalysis, and with a urine protein to creatinine ratio of 27.4 g protein/g creatinine. He experienced worsening renal failure and severe proteinuria over a 2-week period with a peak creatinine of 3.9 mg/dl and a decline in serum albumin from a baseline of 4.2 g/dl to a nadir of 1.1 g/dl (Fig. 1a, b). He had recently initiated sexual activity and engaged in unprotected sexual intercourse with multiple male partners in the 2 months prior to admission. An HIV-1 test was obtained and found to be positive. Of note, laboratory measurements from 4 months prior to admission revealed a creatinine of 0.9 mg/dl. No protein was seen in a urinalysis obtained at that time, but his urine microalbumin level was slightly elevated at 33.2 μg/mg.
A renal biopsy was obtained to assess the marked proteinuria. Nine glomeruli were seen on multiple serial sections, none of which were globally sclerotic. Two glomeruli revealed segmental collapse of the tuft with overlying hyperplastic podocytes (Fig. 1c, d) and electron microscopy showed diffuse, almost complete podocyte foot process effacement. This collapsing FSGS was most consistent with the diagnosis of HIVAN. Surprisingly, his creatinine improved to 1.1 mg/dl 2 months later while his viral load declined from a peak of 24 000 copies/ml to less than 50 copies/ml (Fig. 1a, b). On human leukocyte antigen (HLA) typing, he was found to be HLA-B*5703-positive; this allele is the HLA allele most commonly seen in elite suppressors or controllers of African descent .
The clinical history and the relatively low-level viremia  suggest that he developed HIVAN during primary HIV-1 infection, which resolved spontaneously as his immune response suppressed viral replication. The patient continued to have trace proteinuria with a urine protein to creatinine ratio that ranged from 0.16 g/g to 0.94 g/g over the next 3 years. A subsequent biopsy was, thus, obtained. Of 20 glomeruli observed, eight had evidence of global sclerosis and six were found to be segmentally sclerosed. There was no visible glomerular collapse or podocyte hypertrophy seen (Fig. 1e, f). Electron microscopy showed segmental podocyte foot process effacement involving 50% of the capillary surface. These findings were consistent with a typical (noncollapsing) FSGS.
This is a case of a patient who presented with HIVAN during primary infection who became an elite suppressor or controller and has maintained undetectable viral loads for more than 4 years. His renal function improved markedly with the spontaneous control of viral replication. Although he has ongoing low-level proteinuria, the repeat biopsy found no evidence of collapsing FSGS. Furthermore, his renal function has been stable in this time period, which is not consistent with persistent HIVAN . It likely that the FSGS seen on the second biopsy is a consequence of the HIVAN seen in the first biopsy, representing a ‘healing stage’ of the more active collapsing lesions seen in the first biopsy. The patient's long-standing sickle cell disease may have also contributed to the lesion seen on biopsy  as suggested by the microalbuminuria seen prior to HIV-1 seroconversion.
This is the first reported case of spontaneous resolution of HIVAN. In this case, improvement of renal function correlated with the decline in viral load. Interestingly, Winston et al.  reported a case of HIVAN in primary HIV-1 infection that improved dramatically with the early initiation of HAART. This case further supports the hypothesis that HIV-1 viral replication plays a direct role in the pathogenesis of HIVAN, and it appears that controlling viral replication by HAART [3,10,11] or by the immune response has the same effect. Thus, in the future, a therapeutic HIV-1 vaccine that inhibits HIV-1 replication may also lower the incidence of HIVAN.
The present study was supported by R01 AI080328 (J.N.B.).
1. Wyatt CM, Klotman PE, D'Agati VD. HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. Semin Nephrol 2008; 28:513–522.
2. Winston JA, Bruggeman LA, Ross MD, Jacobson J, Ross L, D'Agati VD, et al
. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001; 344:1979–1984.
3. Atta MG, Gallant JE, Rahman MH, Nagajothi N, Racusen LC, Scheel PJ, Fine DM, et al
. Antiretroviral therapy in the treatment of HIV-associated nephropathy. Nephrol Dial Transplant 2006; 21:2809–2813.
4. Blankson JN. Effector mechanisms in HIV-1 infected elite controllers: highly active immune responses? Antiviral Res 2010; 85:295–302.
5. Baker BM, Block BL, Rothchild AC, Walker BD, et al
. Elite control of HIV infection: implications for vaccine design. Expert Opin Biol Ther 2009; 9:55–69.
6. Migueles SA, Connors M. Long-term nonprogressive disease among untreated HIV-infected individuals: clinical implications of understanding immune control of HIV. JAMA 2010; 304:194–201.
7. Han Y, Lai J, Barditch-Crovo P, Gallant JE, Williams TM, Siliciano RF, Blankson JN, et al
. The role of protective HCP5 and HLA-C associated polymorphisms in the control of HIV-1 replication in a subset of elite suppressors. AIDS 2008; 22:541–544.
8. Goujard C, Chaix ML, Lambotte O, Deveau C, Sinet M, Guergnon J, et al
. Spontaneous control of viral replication during primary HIV infection: when is ‘HIV controller’ status established? Clin Infect Dis 2009; 49:982–986.
9. Scheinman JI. Sickle cell disease and the kidney. Nat Clin Pract Nephrol 2009; 5:78–88.
10. Lucas GM, Eustace JA, Sozio S, Mentari EK, Appiah KA, Moore RD, et al
. Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study. AIDS 2004; 18:541–546.
11. Scialla JJ, Atta MG, Fine DM. Relapse of HIV-associated nephropathy after discontinuing highly active antiretroviral therapy. AIDS 2007; 21:263–264.
© 2011 Lippincott Williams & Wilkins, Inc.