Research justifies transplants for HIV patients

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Liver and kidney transplant can be justified for carefully selected HIV-positive patients, researchers from the US show. Transplant improved the chances of survival for HIV-positive patients with severe liver disease. Comparison with HIV-negative transplant patients showed that HIV-positive liver patients were more likely to experience organ rejection or die, but the difference in risk for both these outcomes was small.

“The modest increase in risk compared with HIV-negative recipients, as well as the absolute proportion of those who died, and comparability with other transplant populations, support liver transplant as a viable option in carefully selected and managed recipients,” comment the authors. “HIV-positive kidney recipients experienced similar outcomes as their HIV-negative counterparts approximately 5 years post-transplant in all control analyses.”

Approximately 2% of patients with HIV develop kidney failure and end-stage liver disease is an increasingly important cause of death in the HIV-infected population. This means that a growing proportion of HIV-positive patients require kidney or liver transplants. However, it has been questioned if patients with HIV are good transplant candidates.

Investigators from San Francisco therefore designed a study to determine if the prognosis of patients was improved by transplantation and to compare outcomes between HIV-positive and HIV-negative transplant recipients in terms of graft loss and death. The study also examined if any factors were associated with organ rejection of death in patients with HIV, rates of infections and hospitalisation, and the impact of transplant on key HIV markers, including CD4 count and viral load.

The HIV-positive study population consisted of 125 liver and 150 kidney transplant patients who underwent transplantation between 2003 and 2010. Their outcomes were compared with HIV-positive patients who were candidates for liver (n = 148) or kidney (n = 167) transplant who received care in the same period but who did not receive a new organ. The kidney patients had a CD4 cell count above 100 cells/mm3 and an undetectable HIV viral load; liver patients had CD4 counts above 200 cells/mm3 and either an undetectable viral load or the possibility of establishing viral control after transplant.

Liver and kidney recipients were followed for a median of 3.5 and 4.0 years, respectively. Candidates were monitored for approximately a year.

Transplant was associated with a significant survival benefit (p < 0.0001) for patients with more severe liver disease (MELD score of at least 15), but not for patients with less severe liver disease or for kidney recipients.

Factors associated with increased mortality risk for liver transplant patients included dual transplant (hazard ratio 3.8, 95% confidence interval 1.6-8.8,p = 0.002), low pre-transplant body mass index, or BMI (HR 2.2, 95% CI 1.1 – 4.4, p = 0.03), older donor age (HR 1.3 per decade, 95% CI 1.1 – 1.6, p = 0.01) and co-infection with hepatitis C virus, (HR 2.1, 95% CI 1.0 – 4.6, p = 0.06). The same factors were associated with graft loss.

Risk factors for increased mortality risk among kidney recipients included older age at the time of transplant (HR 1.07 per decade, 95% CI 1.1 – 1.26, p = 0.01) and therapy with thymoglobulin in in the first week after transplant (HR 3.5, 95% CI 1.3 – 9.1, p = 0.01). Treatment with this drug was also associated with organ rejection (p = 0.048).

Twelve Aids-defining opportunistic infections (cutaneous Kaposi’s sarcoma, esophageal or bronchial candidiasis, PCP pneumonia) were observed in liver transplant patients and four of these individuals died, the causes of death being multi-system organ failure, cerebrovascular accident and recurrent HCV infection.

Three kidney recipients experienced a recurrence of HIV-associated kidney disease. Their CD4 count at the time of recurrence ranged between 0 and 770 cells/mm3.

Serious non-HIV-related infections were observed in 55% of liver and 50% of kidney recipients. Half occurred in the first six months post transplant. For both liver and kidney recipients, most of these infections were bacterial (80% and 71%, respectively). HCV co-infection was associated with an increased risk of infections for both groups of transplant patients.

For liver patients, there was some evidence of post-transplant recovery in CD4 cell count.

Over three years of follow-up, 20% of liver patients and 16% of kidney patients experienced an increase in their HIV viral load to detectable levels. Most, however, subsequently re-established viral control.

The risk of graft-loss and death was compared between the patients with HIV and HIV-negative patients. The investigators conducted four sets of comparison: unmatched, demographically-matched, demographically-matched adjusted for risk score and risk-matched. HIV-negative patients were identified in national databases. Median follow-up was approximately four years.

For kidney recipients, unmatched and risk-matched analysis showed that HIV-positive patients had marginally significant increases in the risk of organ rejection (p = 0.07 and p = 0.52, respectively). All models showed that HIV-positive liver recipients had an increase in the risk of graft loss compared to the controls.

HIV was not associated with an increased risk of death after kidney transplant. HIV-positive liver recipients had an increased risk of death in the unmatched (p = 0.01), demographically-matched (p = 0.01) and demographically-matched risk-score adjusted (p = 0.01) models, but not the risk-matched model. “The absolute difference in the proportion of deaths was 6.7% in the risk-matched control analysis,” note the investigators.

“These analyses support kidney and liver transplantation as an option for carefully selected people with HIV infection,” conclude the authors.

Abstract
Objectives: To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients.
Design: Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls.
Methods: We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models.
Results: There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis.
Conclusion: Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest.

Aidsmap material
AIDS abstract


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