Impact of lamivudine on the risk of liver-related death in 2,041 HBsAg- and HIV-positive individuals: results from an inter-cohort analysis.
BACKGROUND
The impact of lamivudine (3TC) as part of combination antiretroviral therapy (cART) on the risk of liver-related death (LRD) in HIV/hepatitis B virus (HBV)-coinfected patients has not been extensively studied.


METHODS
We performed an analysis involving HIV/HBV-coinfected patients in 13 cohorts who initiated cART. The end-point was LRD--that is, death with concomitant decompensated liver disease (DLD) or hepatocellular carcinoma--as the main cause. Incidence rates of LRD after initiation of cART were expressed as number of events per 100 person-years of follow-up (PYFU). A Poisson regression model adjusted for cohort, gender, mode of HIV transmission, CD4+ T-cell count at cART initiation, liver disease pre-cART, duration of 3TC before cART, and hepatitis C virus was used to assess the association between use of 3TC and risk of LRD.


RESULTS
We analysed 2,041 patients. Follow-up after starting cART was 7,648 PYFU (5,569 spent on 3TC-containing regimens) with a median per person of 48 months (range: 2-91). Of the total, 217 subjects died; 57 deaths were liver-related resulting in a rate of 7.5 per 1,000 PYFU [95% confidence intervals (CI): 5.6-9.7]. The relative risk of LRD per extra year of 3TC use was 0.73 (95% CI: 0.59-0.90, P = 0.004).


CONCLUSIONS
The use of 3TC was associated with a reduced risk of LRD over 4 years of follow-up. This study supports the current view that the use of 3TC as part of cART should be considered in patients who are tested positive for HBsAg.
Puoti
Massimo
M
Clinica di Malattie Infettive e Tropical, Università degli Studi di Brescia, Brescia, Italy. m.puoti@iol.it
Cozzi-Lepri
Alessandro
A
Paraninfo
Giuseppe
G
Arici
Claudio
C
Moller
Nina Friis
NF
Lundgren
Jens D
JD
Ledergerber
Bruno
B
Rickenbach
Martin
M
Suarez-Lozano
Ignacio
I
Garrido
Myriam
M
Dabis
Francois
F
Winnock
Maria
M
Milazzo
Laura
L
Gervais
Anne
A
Raffi
Francois
F
Gill
John
J
Rockstroh
Juergen
J
Ourishi
Nazifa
N
Mussini
Cristina
C
Castagna
Antonella
A
De Luca
Andrea
A
Monforte
Antonella d'Arminio
Ad
D000328:Adult; D018791:CD4 Lymphocyte Count; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006514:Hepatitis B Surface Antigens / Q000097:blood; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008297:Male; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors; D016019:Survival Analysis
D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine