Higher viral load during early pregnancy, poor adherence, associated with increased risk of HIV infection for infants

A higher viral load during the earlier stages of pregnancy is an important risk factor for mother-to-child transmission of HIV, even when a woman’s viral load is below 500 copies/ml at the time of delivery, French investigators report in the February 15^th edition of Clinical Infectious Diseases.

The investigators believe that this finding has implications for the management of HIV during pregnancy, and that “maternal viral load should be controlled well before delivery”.

There is a very low rate of mother-to-child HIV transmission in industrialised countries such as France. Between 1997 and 2004, the transmission rate in France was a little over 1%. Maternal viral load, premature delivery, and short duration of antiretroviral therapy during pregnancy contributed to these transmissions.

However, a small number of transmissions occur when maternal viral load is below 500 copies/ml at the time of delivery. Investigators from the French Perinatal Cohort wished to establish the risk factors for these “residual transmissions”.

They therefore designed a case-controlled study involving women with a viral load below 500 copies/ml at the time of delivery. A total of 19 women (cases) transmitted HIV to their infant and 60 women (controls) did not.

The women gave birth between 1997 and 2006 and all received antiretroviral therapy during pregnancy, and none of the infants were delivered prematurely (before week 37).

Infants were considered to have been infected with HIV in the womb if HIV’s genetic material (DNA) was detected at birth. None of the women breastfed, so any other HIV transmissions were regarded as occurring during delivery.

A number of important differences were noted between the women who transmitted HIV to their infants and those who did not.

Only 16% of cases were taking antiretroviral therapy before pregnancy compared to 45% of controls (p = 0.017). In addition, a higher proportion of women who transmitted HIV to their babies than those who did not reported adherence problems during pregnancy (37% vs 12%, p = 0.005).

Viral load during pregnancy differed significantly between the women who transmitted and those who did not.

The median zenith viral load was significantly higher in the women who passed on HIV to their infants than those who did not (p < 0.001).

During the 30^th week of pregnancy, 42% of women who transmitted HIV to their infant had a viral load above 10,000 copies/ml compared to 11% of those who did not.

Moreover, none of the women who transmitted HIV to their baby had a viral load below 500 copies/ml for the entire duration of their pregnancy compared to 40% of the control mothers.

Viral load was initially higher and decreased more slowly among the women who transmitted. At weeks, 14, 28 and 32, viral load was significantly higher in transmitting women than in controls.

HIV infection was transmitted in the womb in 38% of cases, the other infants being infected during delivery. The investigators suggest that transmission during delivery could be occurring because of shedding of HIV in the genital tract.

A very small number of women (0.4%) had a viral load below 50 copies/ml but still transmitted HIV to their infants, “confirming”, write the investigators, “that there is no threshold under which no residual transmission can occur.”

Statistical analysis showed that higher maternal viral load during week 30 of pregnancy significantly increased the risk of transmission. Women with a viral load above 500 copies/ml at this time were substantially more likely to transmit HIV to their baby than women with a viral load below this level (OR = 23.2; 95% CI, 3.5-552; p < 0.001).

“The only factor…independently associated with residual transmission of HIV was early control of plasma HIV RNA level”, comment the investigators, “although the maternal viral load was below 500 copies/ml at delivery in all mothers, it started to decrease much earlier in control subjects than in case patients.”

The investigators believe that their findings have implications for the care of HIV during pregnancy. They recommend that “HIV load during pregnancy should be monitored closely in order to take measures soon enough, such as reinforcing adherence, therapeutic dose adjustment, or switching for efficient antiretroviral therapy combinations.”

They recommend that guidelines for the prevention of mother-to-child transmission should take into account “baseline maternal plasma viral load for deciding when to start antiretroviral therapy during pregnancy.”