Women with high levels of
hepatitis B viraemia (106IU/ml) who have co-infection with HIV had a more
than sixfold increased risk of having infants with HIV infection compared to
women with HIV alone or co-infected with low levels of hepatitis B viraemia, Dr
Debika Bhattarcharya of the University of California, Los Angeles, told
participants last week at the Conference on Retroviruses and Opportunistic
Infections (CROI 2019)
in Seattle.

In this post hoc analysis of HPTN
046
(a randomised controlled trial evaluating six months of infant
nevirapine vs placebo for prevention of mother-to-child HIV transmission
undertaken in sub-Saharan Africa between 2007 and 2010), high levels of
hepatitis B viraemia also increased the risk of having infants with poor
outcomes including low birth weight.

Hepatitis B virus (HBV) is relatively
common in sub-Saharan Africa with 3-9% of pregnant women living with HIV
affected. Co-infection is linked to lower CD4 cell counts as well as increased HIV
viral load.

Hepatitis B viral load is
associated with hepatitis B transmission during childbirth, as well as poor
long-term outcomes in adults including cirrhosis and liver cancer.

There is conflicting data
about the effect of maternal HBV on maternal and infant outcomes despite the
global burden of hepatitis. Data on HIV co-infection is sparse.

Dr Bhattarcharya and her
colleagues examined the effect of maternal HBV infection on infant and maternal
outcomes in HIV/HBV co-infection. They looked at a study (HPTN 046) conducted at
a time when many women were not on antiretroviral therapy, so as to be able to
isolate the effects of uncontrolled HBV viraemia on these outcomes. They
hypothesised that maternal HBV infection would be associated with adverse
maternal and infant outcomes in this cohort, many of whom presented late to
care.

Maternal samples were
retrospectively tested for hepatitis B surface antigen and if positive tested
for hepatitis B ‘e’-antigen at study entry and hepatitis B viral load at delivery.
High and low hepatitis B viral load was defined as ≥106IU/ml and ≤106IU/ml,
respectively.

Of the 2016 mothers with 2041
infants included in the analysis, 88 mothers  (4.3%) had HIV/HBV co-infection. Their 88 infants
were evenly distributed between having received nevirapine or placebo.

The age for all women was
similar with a median of 27 (IQR: 23-31) years.

As seen in other cohorts CD4
counts at entry were lower among women with high levels of hepatitis B viraemia
(320 cells/mm3) compared to women with HIV alone (490 cells/mm3)
or HIV and low levels of hepatitis B viraemia (434 cells/mm3),
p 0.007.

In multivariate analysis,
adjusted for maternal CD4 cell count, age and maternal antiretroviral therapy, infants born to
mothers with high levels of hepatitis B viraemia were more likely to be of a low
birth weight (30%, 3/10) compared to those with HIV alone (10%, 194/1953) or
HIV and low levels of hepatitis B viraemia (6%, 5/78), p = 0.03.

Examining maternal HBV
viraemia and the threshold for low birth weight further, the authors tested and
compared different models. Viral loads above 105IU/ml were
associated with low birth weight.

Similarly, the likelihood of
HIV infection among those with high levels of hepatitis B viraemia was greater
(20%, 2/10) compared to HIV alone (4%, 53/1953) and low levels of HBV viraemia
(0%, 0/78), respectively, p 0.01.  A
shorter time to HIV infection was also linked with a high hepatitis B viral
load.

Whereas low levels of hepatitis
B viraemia were not associated with infant HIV infection, the increased risk of
infant HIV infection among women with high levels was close to sevenfold: hazard
ratio (HR): 6.75, p.004.

The critical point Dr Bhattacharya
stressed is high levels of hepatitis B viraemia. Typically hepatitis B viral
loads are not looked at but only hepatitis B surface antigen status, she added.

Hepatitis B viral load had no
effect on congenital malformation, infant mortality or maternal outcomes.

Dr Bhattacharya concluded hepatitis
B replication among pregnant women with HIV/HBV co-infection increases the risk of
poor infant outcomes and vertical transmission. Reducing maternal hepatitis B
viral load in this population before giving birth has benefits beyond prevention
of perinatal hepatitis B transmission.