Download HIV-Positive*to*HIV-Positive KTP

HIV-Positive–to–HIV-Positive KTP
- Results at 3 to 5 Years
Elmi Muller, M.B., Ch.B., M.Med., Zunaid Barday, M.B., Ch.B.,
Marc Mendelson, M.D., Ph.D., and Delawir Kahn, M.B., Ch.B.,Ch.M.
N Engl J Med 2015;372:613-20.
DOI: 10.1056/NEJMoa1408896
R2. 이성곤/pf. 임천규
Back-ground

South Africa: highest incidences of HIV
: Anti-retroviral therapy(ART)
 HIV-associated nephropathy Dx.↑
(8~22%-receiving Tx., 20~27%-untreated)

Renal-replacement therapy:
 HIV-associated CKD ↑
: HIV(-)  HIV(+) ≒ HIV(-)  HIV(-)
: 4 HIV(+) donors  HIV(+) recipients
100% graft survival & pt. survival at 1 yr.
5yrs f/u?
(Groote Schuur Hospital, Cape Town.)
Method(1)
1) Study design

Groote Schuur Hospital: KTP- 50 ~ 70
[living donors (30%)/deceased donors (70%)]
In 2008, the first 4 HIV(+) donors  HIV(+) recipients
: the human research ethics committee of the Faculty of
Health Sciences at the University
 Review of the inclusion criteria, protocols & procedures

In 2009, the exclusion of HIV infected persons from the
general KTP program was lifted
 prospective, non-randomized study and all the participants
provided written informed consent (2008.10~2014.2)

Method(2)
2) Donor selection
: All HIV-infected deceased donors
① No living donors
② HIV infection?: 4th-generation enzyme-linked Immunosorbent assay
(ELISA, Abbott).
③ Had not received ART
or receiving 1st-line Tx. & HIV RNA viral load (<50 copies/ml)
④ Exclusion criteria: Severe sepsis, active Tb.,
WHO stage 4 HIV disease (i.e., [AIDS]),
& abnormal renal function
[sCr. level↑, proteinuria on the urine dipstick
or microalb./Cr. ≥ 300μg/mg (or≥3.4mg/mmole)]

All donor kidneys were biopsied at the time of implantation.
Method(3)
3) Recipients
: receiving ART for at least 3 mo.,
CD4 T-cell ≥ 200/cubic mm
& undetectable plasma HIV RNA viral load.
**Pts. Hx.: any opportunistic infection (AIDS were excluded.)
(Pts. with a history of drug-sensitive Tb. were included only after 6 mo. of Tx.)
4) Immunosuppression
① Antibody induction therapy with rabbit anti-thymocyte globulin
(either Thymoglobuline[Sanofi]: 1.5 mg/kg of Bwt./day for 5~7 days,
or ATG [Fresenius]: 2 mg/kg /day for 5~7 days)
② Maintenance therapy
* Day 0 – prednisone: 30 mg/day, tapered ~ 5 mg/day
* Over the first 3 mo. after transplantation,
-Mycophenolate mofetil: 1g q12 hours
-Tacrolimus: started at 0.2 mg/kg(maintain trough levels btw. 6~8 ng/ml)
Method(4)
5) Anti-retroviral therapy

NNRTI(non-nucleoside reverse-transcriptase inhibitor)
 Boosted protease inhibitor–at the time of t/p
(ritonavir: calcineurin-inhibitor metabolism)
 Donor-virus replication↓ + lower the costs advantage
6) Prophylaxis of opportunistic infection
① TMP/SMX 80/400mg daily to prevent PCP
② INH 300 mg once daily, to prevent M. tuberculosis.
③ Valganciclovir 900mg daily
(adjusted according to renal function),
: 1st 3 mo. to prevent CMV reactivation.
Result(1)
1) Donor
23 HIV-infected potential donors
(22 brain-dead + 1 circulatory death)
 6 were excluded
(∵ Infection, proteinuria or Tb.)
 2 were excluded(the Ethics committee.)
= 15 (13 trauma+1 overdose+1 SAH)
Median age: 30 years(IQR, 23~36)
Only 1 donor had been receiving ART
(NNRTIbased 1st-line therapy)
*NNRTI nonnucleoside reverse-transcriptase inhibitor
2) Recipient
: Censored at the time of a pt’s death
Result(2)
93%
cf) HIV(-) pts.
88%
75%
84%
3) Patient and graft survival
*2 /27 : delayed graft function
& required dialysis during the 1st wk.
① Venous thrombosis on day 1,
84%
② Acute severe Ab.-mediated
rejection,
74%
(refractory to plasmapheresis)
**5 pts. died after t/p
(despite a functioning graft)
cf) HIV(-) pts.
91%
: Sepsis & acute pancreatitis(1 mo.)
85%
(E. coli & pseudomonas
species)
①1st
 removal of the graft after 2 wks.
②2nd died of a MI( 6 mo.)
**25 pts.: well-functioning ~ the 1st yr
③ Infection(~1st year)
(3rd recurrent UTI CRKP
+4th pul. aspergillosis)
The median level
sCr at 1yr: 111.5 μmol/L(=1.3 mg/dL)
[(IQR 102.5~117.0 μmol/L(=1.2~1.3 mg/dL)]
④5th died of lung ca.(SCC)( 5 yrs.)
Result(3)
4) Allograft rejection
: 8 episodes of biopsy-confirmed acute rejection occurred in 5 pts.
[Rejection rates= 8%(1 yr) & 22%(3yrs)]
*6/8 episodes : reversed MPD
+ ATG or Thymoglobuline or plasmapheresis.
*2 Graft failure
= Acute severe Ab.-mediated rejection + chronic rejection(scarring & fibrosis)
Result(4)
5) PHARMACOLOGIC INTERACTIONS
*Median tacrolimus dose : trough level 6.0~8.0 mg/ml
① Protease inhibitor–based regimen: 0.5 mg every 7~10 days
② NNRTI-based regimen: 8.5 mg (IQR, 7.0 ~ 11.0) every 12 hrs
*S/E: Pts. receiving a protease inhibitor–based regimen,
5 of whom had evidence on renal biopsy of calcineurin-inhibitor toxicity
Result(5)
6) PROGRESSION OF HIV DISEASE
① CD4 T-Cell Counts
: decreased to 179 cells/cubic mm(IQR, 141~310)( 1st yr)↓
: slow increase to 386 cells/cubic mm(IQR, 307~484)(3 yrs)↑
② Viral Load
: ART before surgery < 50 copies/ml  remained suppressed during f/u
③ Histologic Findings
: 3 pts  Typical of early HIV-associated nephropathy
(Prominent epithelial cells and protein reabsorption granules within the
podocytes, as well as central mesangial sclerosis & cells in the mesangium↑)
④ Infection and Hospitalization
- 6 episodes: UTI in 3 pts.(Patients3, 12, and 16), OM(Patient 1),
URI (Patient 3), AGE(Patients 3, 16, 23, and 25),
Meningitis (Patient 3) & Extrapulmonary Tb. (Patient 10).
- 3 pts. had infectious complications that led to death