Immunisation doesn't prevent mother-to-child HIV transmissions, but approach should not be abandoned, says expert

An experimental immunisation does not confer any addition protection against mother-to-child transmission of HIV compared to single-dose nevirapine, investigators report in the December 1^st edition of the Journal of Acquired Immune Deficiency Syndromes.   

The phase III, randomised study was conducted in Uganda and was designed to determine the safety and efficacy of an experimental HIV hyperimmune globulin (HIVIGLOB) immunisation to prevent mother-to-child transmission of HIV.

“Our trials findings do not support a role for the use of HIVIGLOB to help reduce peripartum and early breast milk transmission of HIV,” comment the investigators.

All the women received single dose nevirapine during labour and their infants were provided with the drug within 72 hours of birth. Provision of HIVIGLOB did not reduce the risk of mother-to-child transmission, but appeared safe.

Nevertheless, the author of an editorial that accompanied the study was encouraged by its findings. Dr Lynne Mofenson of the United States National Institutes for Health suggested that the fact that the trial was conducted at all was promising, and that its results provide some important pointers for future research.

She argued that the results of the study show that it is feasible to conduct a study of this type of intervention, and that newer monoclonal antibody candidates ought to be tested to determine whether an immunisation strategy can improve the efficacy of more up-to-date regimens for prevention of mother-to-child transmission.

It is estimated that 370,000 children were newly infected with HIV in 2009. Over 90% of these infections occurred in sub-Saharan Africa and most were from a mother to her infant.

Mother-to-child transmission of HIV can occur in the womb, during delivery and during breastfeeding. The majority of transmissions during breastfeeding occur during the first six weeks of life.

However, breastfeeding has an overall protective effect on infant survival in many settings. The provision of potent antiretroviral to mothers and infant prophylaxis has been shown to reduce the risk of transmission at this time.

It has been suggested that the use of immune globulin interventions alongside antiretroviral treatment could reduce the risk further.

Early studies suggested that the use of HIVIGLOB could significantly reduce infectivity across a wide spectrum of HIV subtypes. The product was developed using plasma obtained from asymptomatic HIV-positive women in Uganda whose CD4 cell count was above 500 cells/mm³.

Investigators wished to see if the HIVIGLOB product in addition to single-dose nevirapine for mothers and infants provided additional benefits compared to the current standard of care, single dose nevirapine. They also wanted to establish if the product was safe and effective.

All the women enrolled in the study received a 200 mg dose of nevirapine during labour, and their infants received 2 mg/kg of nevirapine syrup within seven days of birth.

Women in the treatment arm also received a 240 ml infusion of HIVIGLOB between weeks 36 and 38 of pregnancy. Their infants were dosed with a 24 ml infusion within 18 hours of delivery.

The primary endpoint was rates of infant HIV infection in the two study arms six months after birth. The rates of infection at delivery, at week two, week six and week 14 were also monitored.

There were a total of 198 mother-infant pairs in the HIVIGLOB arm compared to 294 pairs in the single-dose nevirapine control arm.

All the women reported breastfeeding at week one. But this had fallen to approximately 65% by week 14 and fell futher by month six to between 31% and 33%.

At the time of birth, 9% of infants in the HIVIGLOB arm were infected with HIV compared to 4% of infants in the control arm. This difference was significant (p = 0.03).

This difference in transmission rates persisted until month six, but then ceased to be significant. At this time 19% of infants in the treatment arm were infected with HIV compared to 15% of children in the control arm.

The investigators suggest that HIVIGLOB may not have had activity against HIV subtype D, the second most common subtype in Uganda. “Antibody responses are often very specific to the individual strain with which one is infected and may not have activity against other strains of the virus.”

Alternatively, they suggest that concentrations of HIVIGLOB in “blood cord, vaginal fluids, or breast milk was not sufficient to inhibit virus at different time points.”

A baseline maternal viral load above 100,000 copies/ml was associated with a five-fold increase in the risk of transmission compared to a baseline viral load below 10,000 copies/ml.

Six-month infant mortality rates were broadly comparable between the two study arms (5.6% vs. 3.4%).

The risk of infant mortality was significantly lower for children whose mothers had a CD4 cell count above 350 cells/mm³ compared to infants whose mothers had a CD4 cell count below 200 cells/mm³ (p = 0.045).

The cumulative incidence of infant HIV transmission and death was significantly lower in the control arm compared to the HIVIGLOB arm (10% vs. 17%, p = 0.03) at week two. A similar trend was observed at all other time points but was not significant.

In both arms of the study, 19% of mothers experienced a serious side-effect. Rates of serious side-effects in infants were also comparable (HIVIGLOB, 63% vs. control arm, 60%).