Starting antiretroviral treatment with Trizivir (abacavir, zidovudine and lamivudine fixed dose combination) almost immediately after beginning TB treatment does not appear to result in an increased rate of TB-associated immune reconstitution illness when compared with deferred treatment, according to a pilot study conducted in Tanzania and presented last month at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver.
The optimal time to start antiretroviral treatment in people receiving treatment for TB is still unclear, and delayed therapy is recommended due to interactions between nevirapine and rifampicin (a drug used during the first two months of TB treatment), and because of concerns about immune reconstitution illness associated with TB.
Due to its low pill burden and lack of interaction with the TB drug rifampicin, Trizivir has been proposed as an alternative to efavirenz-containing regimens among patients coinfected with HIV and tuberculosis.
The Tuberculosis and HIV Immune Reconstitution Syndrome Trial (THIRST) randomised antiretroviral-naïve individuals who had begun TB therapy less than 14 days before entering the study to begin antiretroviral treatment with Trizivir immediately or wait for two months. The study followed patients for 104 weeks of antiretroviral treatment.
The study recruited 70 HIV-positive patients with smear-positive pulmonary tuberculosis in the Kilimanjaro region of northern Tanazania with a median baseline CD4 cell count of 106 cells/mm3 in the immediate treatment group and 104 cells/mm3 in the deferred group. Patients with anaemia were excluded from the study due to the use of zidovudine, a drug which can worsen the condition.
Patients in the study were hospitalised for the first eight weeks of antiretroviral treatment in order to allow careful ascertainment of TB-associated immune reconstitution phenomena, but no cases of TB-associated immune reconstitution syndrome were observed during the hospitalisation period or indeed throughout the 727 patient months of follow-up in this study.
Three deaths occurred in the study, all in the immediate treatment arm (one from cerebral malaria, one from disseminated Kaposi’s sarcoma and one from respiratory failure). Four discontinuations due to suspected abacavir hypersensitivity reaction occurred, and two discontinuations due to zidovudine-related anaemia.
CD4 cell counts rose by a median of 113 cells/mm3 during the follow-up period, but the CD4 cell increase was not as great as would be expected in efavirenz-treated patients, leading the authors to speculate that the slope of CD4 cell immune reconstitution may influence the risk of TB-associated immune reconstitution illness. Investigations are continuing among the study population to determine why no cases of TB-associated immune reconstitution illness were seen.
Although the triple nucleoside combination of abacavir/zidovudine/lamivudine was associated with a poorer virologic response in the ACTG A5095 study when compared with AZT/3TC/efavirenz, the study authors did not present any information on virological efficacy of Trizivir during the lengthy follow-up period.
Shao HJ et al. Randomized trial of early vs delayed fixed dose combination zidovudine/lamivudine/abacavir in patients coinfected with HIV and tuberculosis: early findings of the Tuberculosis and HIV Immune Reconstitution Syndrome Trial (THIRST). Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 796, 2006.