|HIV drugs||AZT/PIs||Side effects||Liver toxicity|
|Hepatitis B or hepatitis C virus infection is a risk factor for severe hepatic cytolysis after initiation of a protease inhibitor-containing antiretroviral regimen in human immunodeficiency virus-infected patients.|| ||Saves M, Raffi F, Clevenbergh P, Marchou B, Waldner-Combernoux A, Morlat P, Le Moing V, Riviere C, Chene G, Leport C.
| ||"In a cohort of 1,047 human immunodeficiency virus type 1-infected patients started on protease inhibitors (PIs), the incidence of severe hepatic cytolysis (alanine aminotransferase concentration five times or more above the upper limit of the normal level >/= 5N) was 5% patient-years after a mean follow-up of 5 months."|
| ||Antimicrob Agents Chemother 2000 Dec;44(12):3451-5||2000|
|Serious adverse events attirbuted to Nevirapine regimens for postexposure prophylaxis after HIV exposures|| ||US Centers for Disease Control & Los Angeles County Department of Health Services
| ||“FDA received reports of 22 cases of serious adverse events related to NVP [Nevirapine/Viramune] taken for PEP from March 1997 through September 2000. These 22 events included hepatotoxicity (12)…”|
| ||CDC worldwide 1997-2000. MMWR. 2001 Jan 5;49(51):1153-6.||2000|
|Lactic Acidosis and Hepatic Steatosis Associated with Use of Stavudine: Report of Four Cases.|| ||Miller KD et al.
| ||“An uncommon but life-threatening syndrome of severe hepatic steatosis ... among patients infected with HIV-1 was first described in the early 1990s. By early 1994, at least 40 such cases had been reported to regulatory authorities, and an association with use of zidovudine and didanosine was established. An underlying mechanism involving impaired replication of mitochondrial DNA was proposed. Although stavudine (Zerit, Bristol-Myers Squibb, Princeton, New Jersey) is the second most widely prescribed antiretroviral nucleoside analogue, it has rarely been associated with the syndrome of severe hepatic steatosis... We report on four patients who developed this syndrome while receiving an antiretroviral regimen containing stavudine.”|
| ||Ann Int Med. 2000 Aug 1;133(3):192-6.||2000|
|Hepatotoxicity after introduction of highly active antiretroviral therapy.|| ||Rodriguez-Rosado R et al.
| ||“Hepatotoxicity is frequently seen in patients under HAART, and can force the withdrawal of antiviral treatment in a significant proportion of patients, occasionally resulting in fatal outcome”|
| ||AIDS. 1998 Jul 9;12(10):1256.||1998|
|Hepatotoxicity associated with antiretroviral therapy in adults infected with Human Immunodeficiency Virus and the role of Hepatitis C or B virus infection.|| ||Sulkowski MS et al.
| ||“Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients...Risk of severe hepatoxicity was 5-fold higher for patients taking [the protease inhibitor] ritonavir, which accounted for half of all cases...”|
| ||JAMA. 2000 Jan 5;283(1):74-80.||2000|
|Adverse Effects Associated With Use of Nevirapine in HIV Postexposure Prophylaxis for 2 Health Care Workers [first case]|| ||Johnson S, Baraboutis JG.
| ||“A severe hypersensitivity reaction is a known complication of nevirapine and can present as a fulminant hepatitis.”|
| ||JAMA. 2000 Dec 6.||2000|
|U.S. WARNS ON SOME USE OF A FIGHTER AGAINST H.I.V.|| ||Lawrence K. Altman
| ||"Nevirapine is still used for two other groups, the centers said. One is in treating people infected with H.I.V., the AIDS virus. The second is to prevent transmission of H.I.V. from mothers to their infants during childbirth… Federal health officials advised doctors yesterday not to prescribe a standard H.I.V. prevention drug to healthy health care workers stuck by needles... The agency said it and the federal Food and Drug Administration had identified 22 cases of severe liver, skin and muscle damage related to nevirapine taken after possible exposure to H.I.V. from March 1997 through September 2000 [for a relatively short period of time (2 weeks, on average, before onset of symptoms)]."|
| ||The New York Times 5 Jan. 2001||2001|
|Severe hepatitis in three AIDS patients treated with Indinavir|| ||Braeu N, Leaf H L, Wieczorck R L and Margolis D M
| ||No abstract / Pubmed|
| ||Lancet 1997, 349 924–925||1997|
|NEW AIDS DRUGS STILL A DISTANT GLIMMER|| ||Maugh Thomas
| ||"Particularly alarming to physicians at the recent meeting is the growing incidence of liver disease caused by co-infection by the hepatitis B and C viruses. "We're becoming liver doctors as much as anything else," said Dr. David Stone, an AIDS treatment specialist at Lemuel Shattuck Hospital in Boston. "Fifty percent of our patients' deaths since 1999 have been from liver disease." But the side effects of the drugs and the growing resistance of the virus to therapy have dampened enthusiasm. Many of the side effects of therapy have been attributed to the protease inhibitors specifically, especially increases in cholesterol levels and dysfunctions in fat metabolism."|
| ||Los Angeles Times 11 March 2002||2002|
|Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996–1998. Groupe d'Epidemiologie Clinique de Sida en Aquitaine (GECSA)|| ||Saves M, Vandentorren S, Daucourt V, Marimoutou C, Dupon M, Couzigou P, Bernard N, Mercie P and Dabis F
| ||To study hepatic cytolysis in patients treated by highly active antiretroviral therapy (HAART) with protease inhibitor or with two nucleoside reverse transcriptase inhibitors (NRTIs). We selected patients of the Aquitaine Cohort who initiated HAART or two NRTIs before 1 January 1998, had alanine amino-transferase (ALT) < or = 200 IU/I at baseline and at least one follow-up measure. Cox model was used to study the association between occurrence of severe hepatic cytolysis (ALT>200 IU/l) and age, gender, HIV transmission group, baseline CD4 and CD8 cell count, history of hepatic cytolysis, antiretroviral drug, baseline liver enzymes (WHO classification level 0: < or = 50 IU/l, level 1: 51 to 100, level 2: 101 to 200), hepatitis B and C co-infection. Sixty-four of 748 (8.5%) patients treated with HAART and 71 of 1249 (5.7%) treated with two NRTIs developed cytolysis. The probability of occurrence was 7.9% after 1 year [95% confidence interval (CI), 5.9-10.4] for patients treated with HAART and 4.8% (95% CI, 3.6-6.4) for patients treated with two NRTIs (log-rank test, P = 0.01). The median time to occurrence was 164 days for HAART-treated patients and 252 days for those treated with two NRTIs. In multivariate analysis, the history of cytolysis [hazard ratio (HR) = 2.3; 95% CI, 1.2-4.4], baseline value of ALT (HR = 2.4; 95% CI, 1.2-4.8 and HR = 3.3; 95% CI, 1.4-7.4 for levels 1 and 2, respectively), hepatitis B (HR = 3.0; 95% CI, 1.4-6.2) and C co-infections (HR = 3.2; 95% CI, 1.7-6.2) remained significantly associated with the occurrence of severe hepatic cytolysis among HAART-treated patients. History of cytolysis, hepatitis B and C were associated with cytolysis in patients treated with two NRTIs (HR = 14.8, 2.6 and 2.7, respectively). Hepatic cytolysis is more frequent among patients treated with HAART than with two NRTIs. Hepatitis B and C are the major risk factors after initiation of HAART or treatment with NRTIs. Co-infections with hepatitis B virus or hepatitis C virus may modify the management of HIV-infected patients treated by HAART.|
| ||Aids 1999, 13 F115–121||1999|
|Liver disease raises questions for AIDS patients.|| ||No author
| ||“Liver disease has become the leading cause of death among HIV patients at a Massachusetts hospital, a report issued on Friday...[by] Dr. Barbara McGovern, a professor at Tufts University School of Medicine and a member of staff at Lemuel Shattuck Hospital in Jamaica. The findings were reported on Friday at the annual meeting of the Infectious Diseases Society of America in Philadelphia. McGovern said HIV patients who take a powerful combination of AIDS drugs called highly active antiretroviral therapy (HAART) were at particular risk because of the drug's potential toxicity to the liver. One-third of HIV patients with underlying liver disease at Lemuel Shattuck have had to stop taking HAART.”|
| ||Reuters. 1999 Nov 19.||1999|
|Liver Function Tests Independently Predict Survival|| ||Youle Mike
| ||According to the Justice and European EuroSIDA cohort liver function tests are more accurate predictors of illness and death in HIV positives than viral load tests or T cell counts. Liver toxicity is a well known side effects of AIDS drug treatment. Liver damage is not blamed on HIV.|
| ||Medscape coverage of: XIV International AIDS Conference, 2002||2002|
|No title|| ||Justice Amy
| ||The "most common cause of death among HIV positive people (being treated with AIDS meds) is liver failure. The study bases its conclusions on a study following nearly 6,000 HIV-positive diagnosed patients at four sites in the United States. AIDS establishment scientists have never claimed that HIV damages the liver and the authors admit that liver damage is associated with HAART. Justice said that to the best of her knowledge, her study is the only one that reliably recorded actual cause of death in AIDS patients.|
| ||presentation at the 14th International AIDS Conference in Barcelona||2002|
|Liver failure after long-term nucleoside analogue therapy.|| ||1
| ||“In conclusion, we believe that our patient developed liver failure and portal hypertension in the absence of cirrhosis because of long-term nucleoside-analogue therapy without development of symptomatic lactic acidaemia. Gliclazide and metformin are not related to hepatocellular damage; however, tuberculostatic drugs used might have accelerated this process. This case suggests that even mild hyperlactaemia, which occurs in 15-35% of nucleoside-analogue-treated patients, can be associated with progressive liver damage”|
| ||Lancet. 2001 Sep 1;358(9283):759.||2001|
|Fatal portal hypertension, liver failure, and mitochondrial dysfunction after HIV-1 nucleoside analogue-induced hepatitis and lactic acidaemia.|| ||Carr A et al.
| ||“Acute hepatitis with lactic acidosis is a life-threatening but [sometimes] reversible toxic effect on mitochondria of HIV-1 nucleoside-analogue treatment [later this letter notes that 80% of patients with lactate greater than 10 mmol/L die]. We report fatal portal hypertension, liver failure, and persistent mitochondrial dysfunction in a man aged 65 years with HIV-1 infection who had recovered from nucleoside-analogue-induced acute hepatitis and lactic acidaemia more than 18 months previously. We believe that symptom-free patients who receive nucleoside-analogue therapy should have hepatic [liver] function constantly monitored, especially those with past or present lactic acidaemia. ”|
| ||Lancet. 2001 May 5;357:1412.||2001|
|High Rate of Severe Liver Toxicity Associated With Antiretroviral Therapy.|| ||No author
| ||“A comprehensive retrospective review of more than 10,000 adult AIDS patients participating in 21 different AIDS Clinical Trials Group (ACTG) studies [confirms]... that antiretroviral therapy is associated with a high rate of severe hepatotoxicity [liver damage], regardless of drug class or combination. Dr. Chung of Massachusetts General Hospital in Boston presented the findings to the Digestive Disease Week annual meeting...The researchers evaluated data for AIDS patients, enrolled in ACTG studies between 1991 and 2000. The subjects were taking a variety of drug combinations including one or more nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)...Overall, 10% of patients developed grade 3 and 4 hepatotoxicity and 23% of them had to discontinue therapy permanently. According to the data, 2.5% of all deaths in the study period were liver related. NNRTI [non-nucleoside reverse-transcriptase inhibitors]-containing regimens, especially those including nevirapine and efavirenz, were particularly hard on the liver, with high rates of discontinuation.”|
| ||Reuters Health. 2001 May 23.||2001|
|HBV-drug deaths prompt restudy of similar antivirals.|| ||Touchette, N.,
| ||AZT induces liver damage and may cause hepatic failure and death|
| ||J. NIH Res. 5:33-35. 1993.||1993|
|Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: the role of hepatitis B and C virus infection.|| ||Aceti A, Pasquazzi C, Zechini B, De Bac C; The LIVERHAART Group.
| ||To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV-infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients...|
| ||J Acquir Immune Defic Syndr. 2002 Jan 1;29(1):41-8||2002|