No difference in post-liver transplant survival between HAART-treated HIV-positive and HIV-negative

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HAART-treated, HIV-positive individuals who have a liver transplant are just as likely as HIV-negative patients who receive a replacement liver to be alive after twelve months, according to a prospective US study published in the November 15th edition of the Journal of Infectious Diseases.

However, investigators found that survival was significantly poorer in patients who were unable to tolerate antiretroviral therapy post-transplant, who had a CD4 cell count below 200 cells/mm3, a viral load above 400 copies/mL, or who were coinfected with hepatitis C virus (HCV).

Investigators from five US hospitals prospectively followed 24 HIV-positive individuals who underwent a liver transplant for end stage liver disease after the introduction of HAART, between 1997 and 2001. Fifteen individual had HCV infection as the cause of end stage liver disease, seven patients had hepatitis B virus (HBV) as the cause, and three patients had fulminant liver failure in association with nevirapine-induced liver necrosis, acute hepatitis A virus infection and acute HBV infection.

Glossary

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

sample

Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

end-stage disease

Final period or phase in the course of a disease leading to a person's death.

Patients were not excluded on the basis of CD4 cell count, viral load, or past opportunistic infection, but could not have a current opportunistic infection at the time of transplant.

Anti-HIV therapy had been used by all but two patients prior to transplant, and median preoperative CD4 cell count was 188 cells/mm3 and median viral load was below 400 copies/mL.

HAART was recommenced within three weeks of transplant once liver function was within normal range. Fourteen patients were prescribed a regimen including a protease inhibitor, five a non-nucleoside (NNRTI), and four received only nucleoside analogues (NRTIs).

The study patients were followed for a median of 17 months, and at the time of last follow-up median CD4 cell count was 281 cells/mm3 and median viral load was below 400 copies/mL. However, a total of six patients (26%) could not tolerate antiretroviral therapy after transplant and four of these died. All four patients were coinfected with HCV, and experienced a recurrence of HCV disease, requiring anti-HCV therapy in two cases. One of the patients who died also required antifungal therapy.

At twelve months, 87.1% of individuals were still alive; this was comparable to the 86% survival seen in age-matched HIV-negative liver transplant recipients (p=0.365). At 24 and 36 months a little under 73% of the HIV-positive patients were still alive compared to survival probabilities of 81% and 78% for HIV-negative liver transplant recipients.

Investigators noted that patients who were unable to tolerate anti-HIV therapy post-transplant were significantly less likely to survive (p=0.044). Survival was also poorer amongst patients whose last available post-operative CD4 cell count was below 200 cells/mm3 (p=0.005), or who had a viral load above 400 copies/mL (p=0.016). The investigators comment that these findings “suggest the importance that post-operative viral suppression and an increase in CD4+ count have for survival.”

Investigators also noted a trend for poorer survival amongst patient who received only NRTI therapy after transplant (p=0.91), but also found that neither a CD4 cell count below 200 cells/mm3 (p=0.602), nor viral load viral load above 400 copies/mL (p=0.494) prior to transplant predicted poorer survival.

Survival was significantly poorer amongst patients coinfected with HCV (50% versus 100%, p=0.023). The authors comment that the small sample size in the studymakes it impossible to determine whether any other confounding factor may have affected survival in HIV-infected patients and they note that no survival difference was detected in 5,225 HIV-negative historical controls from the UNOS Scientific Registry of Liver Transplantation.

The investigators conclude “the major finding of this study is that successful liver transplantation is possible in HIV-infected subjects and that, for HIV-infected subjects post-[operative] survival with antiretroviral therapy is similar to that in HIV-negative subjects.” However, they note the small size of their study sample and call for further studies.

An editorial accompanying this study argues that HIV-positive patients who are able to tolerate HAART after transplant should be considered good candidates for transplant. The editorial also suggests “larger, multicenter, prospective trials must be performed to study liver transplantation among HIV-infected individuals with or without HCV infection. These must be performed with standardized approaches to immune suppression, treatment of graft rejection, and anti-HCV and HAART therapies.”

Further information on this website

Few HIV-positive Italians candidates for liver transplant if strict criteria used - news story

Successful heart transplant in man with advanced HIV disease reported - news story

Organ transplants successful in people with HIV, but concern over drug interactions - news story

References

Ragni MV et al. Survival of human immunodeficiency virus-infected liver transplant recipients. Journal of Infectious Diseases 188: 1412 – 1420, 2003.

Fishman JA. Transplantation for patients infected with human immunodeficiency virus: no longer experimental but not yet routine. Journal of Infectious Diseases 188: 1405 – 1419, 2003.