|HIV drugs||AZT/PIs||Side effects||Anemia|
|Manufacturer's notice|| ||Glaxo SmithKline
| ||"WARNING: RETROVIR (ZIDOVUDINE) MAY BE ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING SEVERE ANEMIA PARTICULARLY IN PATIENTS WITH ADVANCED HIV DISEASE."|
|Pilot study of a combination of highly active antiretroviral therapy and cytokines to induce HIV-1 remission.|| ||Lafeuillade A et al.
| ||“1 patient [out of a grand total of 10 in this 72 week clinical trial of combination therapy with nucleoside analogs (zidovudine-AZT, lamivudine-3TC and didanosine-ddI), Protease Inhibitors (saquinavir and ritonavir) as well as interleukin-2] suffered from severa anemia resulting from ZDV [AZT] therapy and was switched to d4T [another nucleoside analog] at week 20...8 patients had minor gastrointestinal side effects on initiation of HAART.”|
| ||J Acquir Immun Defic Syndr. 2001 Jan 1;26(1):44-55.||2001|
|Review & Evaluation of Pharmacology & Toxicology Data for the drug Retrovir, 29 December 1986.|| ||Chernov Harvey I.
| ||Chernov reviewed several dozen studies that had been completed, including in vitro studies and experiments on rats, mice, rabbits, beagle dogs, and human beings. Many additional studies had not been completed or had been planned but not begun. The single most important finding was that AZT was toxic to the bone marrow, causing anemia. "Thus, although the dose varied, anemia was noted in all species (including man) in which the drug has been tested. In conclusion, the full preclinical toxicological profile is far from complete with 6-month data available, but not yet submitted, one-year studies to begin shortly, etc."|
|Anaemia is an independent predictive marker for clinical prognosis in HIV-infected patients from across Europe. EuroSIDA study group;|| ||Mocroft A, Kirk O, Barton S E, Dietrich M, Proenca R, Colebunders R, Pradier C, dArminio Monforte A, Ledergerber B and Lundgren J D
| ||"To describe changes in haemoglobin over time and to determine the joint prognostic value of the current haemoglobin, CD4 lymphocyte count and viral load among patients from across Europe. The analysis included 6725 patients from EuroSIDA, an observational, prospective cohort of patients with HIV from across Europe. Normal haemoglobin was defined as haemoglobin greater than 14 g/dl for men and 12 g/dl for women; mild anaemia was 8-14 g/dl for men and 8-12 g/dl for women; severe anaemia was defined as less than 8 g/dl for both males and females. Linear regression techniques were used to estimate the annual change in haemoglobin; standard survival techniques were used to describe disease progression and risk of death. At recruitment to the study, 40.4% had normal levels of haemoglobin, 58.2% had mild anaemia and 1.4% had severe anaemia. At 12 months after recruitment, the proportion of patients estimated to have died was 3.1% [95% confidence interval (CI) 2.3-3.9] for patients without anaemia, 15.9% for patients with mild anaemia (95% CI 14.5-17.2) and 40.8% for patients with severe anaemia (95% CI 27.9-53.6; P < 0.0001). In a multivariate, time-updated Cox proportional hazards model, adjusted for demographic factors, AIDS status and each antiretroviral treatment as time-dependent covariates, a 1 g/dl decrease in the latest haemoglobin level increased the hazard of death by 57% [relative hazard (RH) 1.57; 95% CI 1.41-1.75; P < 0.0001], a 50% drop in the most recent CD4 lymphocyte count increased the hazard by 51% (RH 1.51; 95% CI 1.35-1.70; P < 0.0001) and a log increase in the latest viral load increased the hazard by 37% (RH 1.37; 95% CI 1.15-1.63; P = 0.0005). Severe anaemia occurred infrequently among these patients but was associated with a much faster rate of disease progression. Among patients with similar CD4 lymphocyte counts and viral load, the latest value of haemoglobin was a strong independent prognostic marker for death." (Anemia (low red blood cell levels) is a well known side effects of AIDS drug treatment and not blamed on HIV.)|
| ||Aids 1999, 13 943– 950||1999|
|The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related-Complex.|| ||RICHMAN DD, FISCHL MA, GRIECO MH, et al., and The AZT Collaborative Working Group.
| ||"We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex... Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT;... Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date."|
| ||NEJM 1987; 317:192-197.||1987|
|Physician's Desk Reference|| ||No author
| ||The drug used to treat and prevent CMV retinitis, gancyclovir, has serious immunosuppressive effects, with a bold faced warning in the PDR : "THE CLINICAL TOXICITY OF (GANCICLOVIR) INCLUDES GRANULOCYTOPENIA, ANEMIA, AND THROMBOCYTOPENIA. IN ANIMAL STUDIES GANCICLOVIR WAS CARCINOGENIC, TERATOGENIC, AND CAUSED ASPERMATOGENESIS" (Page 2104).|
| ||Thomson Healthcare||1999|
|Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1.|| ||Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, Berrebi A, Benifla JL, Burgard M, Lachassine E, Barret B, Chaix ML, Bongain A, Ciraru-Vigneron N, Crenn-Hebert C, Delfraissy JF, Rouzioux C, Mayaux MJ, Blanche S; Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study Group.
| ||"To assess the safety of perinatal lamivudine-zidovudine therapy, especially in children, and its effects on viral load, acquisition of drug resistance, and maternal-infant transmission of HIV-1 in a nonbreastfeeding population... A total of 445 HIV-1-infected pregnant women were enrolled as the study cohort from February 1997 to September 1998; controls consisted of 899 pregnant women who had received zidovudine monotherapy in May 1994 to February 1997 as standard care. The study cohort received lamivudine in addition to the standard Pediatric AIDS Clinical Trial Group 076 Study zidovudine prophylaxis regimen... The most frequent serious adverse events in children were ... anemia, requiring blood transfusion in 9 children and premature treatment discontinuation in 19. Two uninfected children died at age 1 year from neurologic complications related to mitochondrial dysfunction."|
| ||JAMA 2001 Apr 25;285(16):2083-93||2001|
|Severe anemia as a newly recognized side-effect caused by lamivudine.|| ||Weitzel T, Plettenberg A, Albrecht D, Lorenzen T, Stoehr A.
| ||No abstract / Pubmed|
| ||AIDS 1999 Nov 12;13(16):2309-11||1999|