Association of HIV replication capacity with mother to child transmission

A poster from Susan Eshleman and coworkers, reported findings from a study looking at the association between HIV-1 replication capacity and HIV-1 mother to child (MTCT) transmission, among antiretroviral naive HIV positive Malawian women, enrolled in the NVAZ trial of women who presented late for delivery [1,2].

This group of subtype C HIV positive women received no antiretroviral prophylaxis. The infants were randomised to receive single dose nevirapine or single dose nevirapine plus one week AZT.

The authors classified women as transmitters if their infants were diagnosed with HIV at birth or by 6-8 weeks, and non-transmitters if their infants were uninfected at 6-8 weeks of age. Fifty two transmitters and 48 non-transmitters were randomly selected from the NVAZ group of 172 transmitters and 780 non-transmitters.

Replication capacity was measured using a modified version of the PhenoSense HIV test. Plasma samples were collected at time of delivery.

Replication capacity results were determined for 49 transmitters and 47 non- transmitters. The mean replication capacity for the maternal plasma samples was 32% (standard deviation = 20%). The mean replication capacity was higher for transmitters 35.3% vs non-transmitters 27.4% (p = 0.02 ), as was mean maternal viral load 5.1 log10 vs 4.6 log 10 (p=0.001).

In a multivariate model, a higher log10 replication capacity was associated with MTCT (OR = 6.60, 95%CI 1.23 to 35.31, p= 0.03), adjusting for log10 delivery viral load (OR = 2.77, 95% CI 1.38 to 5.57, p = 0.0043), maternal age (OR = 1.01, 95%CI 0.88 to 1.16, p = 0.89), parity (OR = 1.34, 95%CI 0.90 to 2.00, p= 0.15), and infant regimen (OR = 0.61, 95%CI 0.23 to 1.61, p = 0.31).

The authors noted that the proportion of infants receiving single dose nevirapine alone was higher among the transmitter group as found in the NVAZ trial.

In this group of Malawian subtype C HIV positive women whose infants received single dose nevirapine or single dose nevirapine plus AZT, maternal viral load was associated with MTCT. The authors wrote: Further studies are needed to confirm the association of replication capacity and HIV-1 transmission in diverse HIV-1 subtypes, in different clinical settings and with different routes of HIV-1 transmission. These results also suggest that determinants in the HIV-1 gag/pol region influence HIV-1 MTCT, since this is the only region of the patients HIV-1 genome inserted into the resistance test vector in the replication capacity assay