HIV and Hepatitis.com Coverage of the
13th Annual Conference on Retroviruses and Opportunistic Infections
February 5 - 8, 2006, Denver, CO

Is Combination Therapy More Effective Than Monotherapy for Chronic HBV in HIV-coinfected Patients?  

By Marina Nunez, MD, PhD

Several nucleos(t)ide analogues reverse transcriptase inhibitors (NRTI) with activity against HBV are currently available or under development for the treatment of HIV/HBV-coinfected patients. Whether the use of dual therapy is more appropriate than [HBV] monotherapy in these patients is unclear at this time.

Investigators from the UK performed a multicenter randomized open-label study to compare the effect of lamivudine (3TC; Epivir-HBV) alone versus tenofovir (TDF) alone versus 3TC+TDF as part of HAART in individuals with HIV-HBV coinfection. In the 3TC arm, TDF was added at week 24 of therapy. Results in 21 naïve patients at weeks 24 and 48 were as follows:

3TC-experienced

3TC-naive

ARM (n)

TDF
(12)

3TC
(9)

TDF/3TC (11)

TDF
(10)

3TC
(11)

TDF/3TC (6)

Median Baseline HBV DNA (log copies/mL)

7.7

8.2

7.7

8.2

7.5

8.2

Median ALT IU/L (range)

48

(39 to 63)

61

(51 to 156)

62

(32 to 118)

77

(47 to 110)

66

(22 to 134)

35

(26 to 45)

Median change in HBV DNA (24 weeks)

–3.41
P <0.001

–0.82

–3.93
p <0.001

–4.66
p = 0.102

–3.31

–5.03
p = 0.045

Median change in HBV DNA (48 weeks)

–3.07

–2.50

–4.50

–5.41
p = 0.562

–4.55

–6.23
p = 0.865

HBV DNA <400 copies/mL   (24 weeks)

2
p = 0.486

0

4
p = 0.094

4
p = 0.998

4

3
p = 0.644

HBV DNA <400 copies/mL       (48 weeks)

4
p = 0.338

1

6
p = 0.070

3
p = 0.198

7

2
p = 0.335

Normalization ALT (<37 IU/L) (48 weeks)

7

5

8

7

9

5

HBeAg negative (48 weeks)

2

0

3

3

5

2

All p values are vs 3TC alone by either naïve or experienced treatment arm.

These data suggest that the best choice for naïve HBV/HIV-coinfected subjects is the combination of TDF plus 3TC as HAART nucleoside backbone. However, while with this small sample superiority of 3TC+TDF over 3TC alone has been proved, the benefit of combined therapy compared to TDF alone remains unclear. Larger studies with long follow-up, including analyses of development of resistance mutations are necessary to elucidate this issue.

In the same study 32 experienced patients were also analyzed. Results at week 24 showed no benefit in continuing 3TC alone (-0.68 HBV DNA log10 decrease) compared to the switch to TDF (-3.76 HBV DNA log10 decrease) (p<0.001) or to the addition of TDF (-3.96 HBV DNA log10 decrease) (p<0.001).

Given the lower genetic barrier shown by 3TC in the selection of resistance mutations in the HBV genome in HIV-coinfected subjects, and the higher potency of TDF, this drug should be given as first choice for the suppression of HBV replication in this setting. Whether to use it alone or combined with 3TC is at the moment a matter to be decided on an individual basis.

02/21/06

Reference
M Nelson and others. A 48 week study of tenofovir or lamivudine or a combination of tenofovir and lamivudine for the treatment of chronic hepatitis B in HIV/HBV coinfected individuals. 13th Conference on Retroviruses and Opportunistic Infections. 5-8 February 2006, Denver, CO. Abstract 831.