Subtype differences in mother to child transmission

Results from a large African mother to child transmission (MTCT) cohort study reported in July AIDS, evaluated the impact of HIV-1 group M subtype variation on transmission rates in this setting where multiple subtypes are circulating.

Women attending an antenatal clinic in western Kenya were enrolled in a prospective study (1996-2000) of MTCT. This trial conducted a subtype analysis of p24gag and gp41env identified potential recombinants, and their role in MTCT was determined.

Among the women for whom HIV-1 subtype and HIV transmission status were available (n=414), transmission occurred in 80/414 (19.3%). The investigators reported higher transmission rates among women with subtype D compared with subtype A in either the gp41 region [31.6 versus 16.1%, relative risk (RR) 2.0, p= 0.002] or p24 region (29.9 versus 18.0%, RR 1.7, p= 0.02). They found subtype A to be most prevalent (73%) compared to subtype D (18.6%) in the gp41 region and also the p24 region – 70.1% and 19.1% subtypes A and D respectively.

The investigators reported that women with discordant subtypes 103/398 (25.9%) in these two regions were more likely to transmit HIV (28.2 versus 17.00%, RR1.7, p=0.01) compared to women with concordant subtypes.

They also found that among women with viral subtype combinations there were significantly higher MTCT rates (p<0.009) among women with D/D, D/A or A/D combinations compared to women with other subtype combinations. Rates were A/A 14.9% in comparison to: D/D 32.4% (RR 2.2 p=0.009), D/A 29.0% (RR 1.9, p=p=0.005) and A/D 42.3% (RR 2.8, p=0.002).

After adjusting for viral load, episiotomy or perineal tear, placental malaria and low birth weight, multivariate analysis revealed women with subtype combinations D/D, D/A and A/D to have an increased risk of MTCT (AOR 3.5, 2.5 and 6.2; p=0.005, 0.05 and 0.0003 respectively) compared to women with A/A viral combination. Transmission rates among women with other subtype combinations were not significantly different to those with A/A combination.

Overall, the authors found MTCT to be significantly more frequent among mothers infected with subtype D compared with subtype A. They hypothesised: “…that viruses with subtype D are either more virulent or have better fitness capacity or altered cellular tropism for placental cells that results in higher MTCT rates.” Or they suggest an alternative explanation may be that “…subtype A viruses are less fit and may be transmitted less efficiently from mother to child.”

The also note that the difference in viral subtypes has a bearing on future MTCT intervention trials using current antiretroviral therapy regimens which were designed on the basis of subtype B viruses. They highlight a recent study in Uganda in which a higher rate of nevirapine resistant mutations were observed in women with subtype D compared to subtype A following single dose nevirapine prophylaxis. They conclude: “Any future intervention trials should thus consider the effect of these subtype-based differences both on transmission efficiency and for the emergence of drug-resistant mutations. These findings may also have relevance to clinical management and effective vaccine design.”

Yang, C; Li, M; Newman R D et al. Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother to child transmission. AIDS 2003, 17:1667 – 1674.