There is a trend for higher rates of mother-to-child transmission of HIV for women infected with sub-type D versus sub-type A, according to data from the HIV Network for Prevention Trials (HIVNET) 012 study published in the August 15th edition of The Journal of Acquired Immune Deficiency Syndromes.
Although this trend was not statistically significant, the investigators also found that the infants of mothers with sub-type D were more likely than those with mothers with sub-type A to be infected after week eight of life. However, this trend was once again not statistically significant.
"We cannot exclude the possibility that nevirapine exerts a differential effect on viral infectivity, replication capacity, or transmissibility in subtype A versus sub-type D", comment the investigators. "Such an effect could contribute to a higher rate of mother-to-child transmission among the subset of infants with sub-type D who were infected after nevirapine dosing."
Results from the Ugandan HIVNET 012 study demonstrated that a single dose of nevirapine (Viramune) given to a mother at the onset of labour and to her infant within 72 hours of birth dramatically reduced the risk of mother-to-baby transmission of HIV. The nevirapine regimen used in the HIVNET 012 study is endorsed by the World Health Organization (WHO) and is the basis of mother-to-baby transmission prevention programmes in resource-limited settings.
Data from other studies suggests that some HIV sub-types are more readily transmitted from a mother to her infants. In Uganda, an equal number of HIV infections involve sub-types A and D, and investigators analysed data from the HIVNET 012 study and compared the rates of mother-to-baby transmission in women infected with sub-types A and D.
All the women were naïve to antiretrovirals prior to being provided with a single dose of nevirapine at the onset of labour. A total of 158 women were infected with sub-type A and 105 women with sub-type D. Rates of mother-to-baby transmission were compared at birth, after eight weeks and after 18 months.
At birth, eight infants (5%) born to mothers with sub-type A were infected with HIV as were nine babies (9%) whose mothers were infected with sub-type D. The difference was not statistically significant.
After eight weeks, the cumulative total of HIV-positive babies of mother with sub-type A was 15 (10%) and twelve infants (12%) of mothers with sub-type D were also HIV-infected at this stage. Once again, the difference was not statistically significant.
By month 18, a total of 20 infants (13%) whose mothers were infected with sub-type A were diagnosed with HIV, as were 18 (18%) of babies with mothers who had HIV sub-type D. As at the other study endpoints, the difference was not statistically significant.-
"Although there was still a trend toward a higher transmission rate among women with sub-type D, the 95% confidence intervals were wide and overlapping", note the investigators.
Differences in mother-to-baby transmission rates were then evaluated further using a Cox proportional hazard model which included maternal pre-nevirapine viral load, CD4 cell count and sub-type as predictors of transmission. Only viral load was found to be a significant predictor of vertical transmission (p = 0.03).
The investigators comment, "results presented in this report show a tendency for a higher rate of mother-to-child transmission among women with sub-type D versus A. This difference was not statistically significant, however."
They caution that the small size of the study cohort and the low rate of mother-to-transmission makes interpretation of the study’s findings difficult, but emphasise that other studies do suggest differing transmission risks between HIV sub-types.
"Further studies are needed comparing mother-to-child transmission rates in larger cohorts of women with different HIV sub-types", conclude the investigators, "studies are also needed to define which regions of HIV are most important and to examine variables such as the timing of transmission and the use of antiretroviral drug prophylaxis."
Eshleman SH et al. Comparison of mother-to-child transmission rates in Ugandan women with sub-type A versus sub-type D HIV-1 wo received single-dose nevirapine prophylaxis: HIV Network for Prevention Trials 012. J Acquir Immune Defic Syndr 39 (5): 593 – 597, 2005.