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Increased risk of HIV transmission to HIV-negative partners during pregnancy

Polly Clayden HIV i-Base

Physiological and behaviour changes during pregnancy may increase risk of HIV transmission. Results from previous studies looking at HIV acquisition in women in pregnancy have been inconsistent. No study has looked at transmission from HIV-positive pregnant women to men directly.

Investigators from the Partners in Prevention HIV/HSV Transmission study – a randomised controlled trial of acyclovir suppressive HSV treatment for the prevention of HIV transmission in serodiscordant African couples – evaluated the relationship between pregnancy and risk of HIV acquisition in women and transmission from women to men. Nelly Mugo and colleagues reported findings from this study in an article published ahead of print in August 2011 AIDS.

There were 3321 couples included in the overall analysis, of these, in 1085 (32.7%) and 2236 (67.3%) couples, the man and the woman were the HIV-positive partner respectively. The median follow up was about 20 months. Pregnancy testing was quarterly.

At enrollment, 94 (8.7%) HIV-negative and none of the HIV-positive women were pregnant (pregnancy was an exclusion criterion for HIV-positive women). Subsequently, there were 226 and 503 pregnancies among the HIV-positive and HIV-negative women respectively, during the study period. This gave an incidence of 15.3 pregnancies per 100 person years, with 1480 person-years of follow up at risk of pregnancy for the HIV-negative women and 16.0 per 100 person-years with 3147 person-years of follow up at risk of pregnancy for the HIV-positive women. A proportion of women (27 from each group) had two pregnancies during follow up and one HIV-positive woman was pregnant three times.

Out of a total of 61 seroconversions among women, 17 (27.9%) were during pregnancy. The incidence of HIV during pregnancy was 7.35 per 100 person years compared to 3.01 per 100 person years during times when the women were not pregnant, HR 2.34 (95% CI 1.33-4.09), p=0.003. In multivariate analysis, this effect of pregnancy on HIV acquisition was weakened and did not reach statistical significance, AHR 1.71 (95% CI 0.93-3.12), p=0.08.

Of the 58 HIV transmissions to men, 12 (20.7%) were during pregnancy. The incidence of female to male HIV transmission was 3.46 per 100 person years during pregnancy compared to 1.58 per 100 person years, HR 2.31 (95% CI 1.22-4.39), p=0.01. This effect remained statistically significant in multivariate analysis, AHR 2.47 (95% CI 1.26-4.85), p=0.01. A subgroup analysis suggested the risk may increase in early and late pregnancy – AHR 2.64 (95% CI 1.02-6.84), p=0.05 and AHR 2.37 (95% CI 1.03-5.46) p=0.04 respectively – but the numbers in the subgroups were tiny (only 5 and 7)

The investigators also examined the use of antiretrovirals among women in pregnancy and the relationship to female to male transmission. Of the 503 pregnancies reported in HIV-positive women 216 (42.9%) resulted in live births, 143 (28.4%) in pregnancy losses, 14 (2.8%) had unknown outcomes and 128 (25.5%) were ongoing at study exit. The investigators noted that 119/143 (83.2%) of the pregnancy losses were before 20 weeks gestation, partly reflecting chemical pregnancies that were detected due to quarterly pregnancy testing in the study protocol.

Of the 216 pregnancies that ended in live births, 176 (81.5%) women received antiretrovirals but only 74 women received combination ART. The remainder received either short course or dual or single agent prophylaxis at the time of delivery. Of the 12 female to male transmissions during pregnancy, 9 (75%) women received antiretrovirals but this coincided with the time of transmission in only two couples. One woman was using short course AZT during labour and the second initiated ART in early pregnancy and her partner seroconverted shortly after. Adjustment for antiretroviral use in pregnancy did not alter the estimated risk of transmission, AHR 2.3 (95% CI 1.15-4.61), p=0.02.

The investigators wrote that this novel finding that pregnancy increases the risk of female to male HIV transmission has important public health implications and requires further studies to understand the possible biological mechanisms.

Reference:

Mugo N et al. Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1 serodiscordant couples. AIDS published ahead of print August 2011.

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