High maternal HBV with HIV tied to low infant weight and HIV transmission
Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle

 

Mark Mascolini

 

Compared with pregnant women infected with HIV only, those with HIV plus high HBV load proved more likely to transmit HIV to their infants and to have infants with low birth weight [1]. This analysis 4000 mothers and infants in HPTN 046 found no link between maternal HBV load and infant mortality or maternal outcomes.

 

Prior research linked HBV coinfection of pregnant women with HIV to lower CD4 count and higher HIV load. Other work tied HBV load to HBV perinatal transmission and long-term outcomes like cirrhosis and liver cancer in adults. But conflicting data have emerged from studies of maternal HBV impact on other maternal and infant outcomes, noted IMPAACT and the HIV Prevention Trials Network (HPTN) researchers who conducted this study. And little work addresses HIV coinfection in pregnant women with HBV. They conducted this post hoc analysis of HPTN 046 to assess the impact of maternal HBV (including HBV load) on mothers with HIV and/or HBV infection and their infants.

 

HPTN 046 was a phase 3 double-blind, placebo-controlled trial testing the efficacy of once-daily nevirapine to prevent perinatal HIV transmission from breast-feeding women in South Africa, Tanzania, Uganda, and Zimbabwe [2]. The HBV analysis included HIV-positive women 18 or older enrolled in HPTN 046 and infants born to all women, regardless of study arm. Researchers retrospectively tested maternal samples for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV viral load. They defined high and low HBV load as a level above or below 1 million IU/mL.

Analysis of 2016 mothers and 2041 infants yielded 88 HIV/HBV coinfected mothers and their 88 infants, and 1928 HIV-monoinfected women with 1953 infants. Among the 88 women with HIV/HBV, 78 had an HBV load below 1 million IU/mL and 10 had a higher HBV load. Median CD4 count was higher in 1928 women with HIV monoinfection than in coinfected women with lower HBV load or higher HBV load (490 vs 433.5 vs 319.5 CD4s, P = 0.007).

 

Similar proportions of women in those three groups received antiretroviral therapy (ART) during pregnancy (78% vs 88% vs 80%), but women in the higher HBV load group received ART significantly longer (median 62 vs 69 vs 93.5 days, P = 0.009). The highest proportion of women received only zidovudine (48%), while 33% received nonnucleoside-based triple therapy and 17% received zidovudine plus lamivudine.

 

Women with a high HBV load (above 1 million IU/mL) were significantly more likely to have infants with low birth weight or with HIV infection at any time:

 

Low birth weight (</=2500 g)

HIV only 10%; HIV/low HBV 6% (not significant vs HIV only); HIV/high HBV 30% (P = 0.04 vs HIV only)

 

Infant HIV infection at any time

HIV only 4%; HIV/low HBV 0% (not significant vs HIV only); HIV/high HBV 20% (P = 0.01 vs HIV only)

 

Low birth weight or infant HIV infection at any time

 

HIV only 13%; HIV/low HBV 6% (not significant vs HIV only); HIV/high HBV 40% (P = 0.02 vs HIV only)

The researchers figured that the maternal HBV load threshold for a low birth weight infant stood at 100,000 IU/mL (odds ratio for low birth weight 9.5, 95% confidence interval [CI] 2.11 to 42.79, P = 0.003). They estimated that a maternal HBV load above 1 million IU/mL conferred more than a 6-fold greater risk of infant HIV infection compared with HIV monoinfection (hazard ratio 6.754, 95% CI 1.862 to 24,501, P = 0.004).

 

High versus low maternal HBV load did not predict congenital malformation, infant death, or two maternal outcomes--duration of ruptured membranes, or episiotomy or primary tears.

 

The IMPAACT/HPTN team believes their findings suggest that "reduction of antepartum maternal HBV viremia may have beneficial effects beyond the prevention of HBV perinatal transmission in HIV/HBV coinfection."

 

References

1. Bhattacharya D, Guo R, Tseng CH, et al. Maternal HBV viremia is associated with adverse infant outcomes in HIV/HBV women. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 41.

2. Coovadia HM, Brown ER, Fowler MG, et al. Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial. Lancet. 2012;379:221-228. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61653-X/fulltext