Pregnancy doubled risk of female-to-male HIV transmission in Partners in Prevention study

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Pregnancy increased the risks of female-to-male HIV transmission twofold among over 3300 serodiscordant couples from seven African countries, Nelly R Mugo and colleagues reported in a prospective study published in the advance online edition of AIDS.

The risks of becoming infected with HIV during pregnancy increased at the same rate. However, this was partly explained by other factors, including unprotected sex.

Women now account for 60% of HIV infections in adults in sub-Saharan Africa. Many African countries with high HIV prevalence also have high fertility rates and often women are pregnant for a considerable proportion of their adult lives.

Glossary

prospective study

A type of longitudinal study in which people join the study and information is then collected on them for several weeks, months or years. 

herpes simplex virus (HSV)

A viral infection which may cause sores around the mouth or genitals.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

serodiscordant

A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

Pregnancy brings biological and behavioural changes that may make a woman more susceptible to getting HIV, as well as making her more infectious, so increasing the risks of transmission.

To date, limited prospective studies have found inconsistent results, showing either an increased risk or no elevated risk of acquiring HIV during pregnancy. However, evidence shows that women infected during their pregnancy have a high rate of HIV transmission to their infants.

The authors note one study which showed increased HIV shedding in genital secretions during pregnancy, suggesting increased infectiousness, yet no prospective study has looked specifically at pregnancy as a risk factor for female-to-male transmission.

The authors chose to look at the association between pregnancy and the risks of getting HIV, as well as the risks of transmitting HIV from females to males, in a secondary analysis of a prospective study of African HIV serodiscordant couples.

From November 2004 to April 2007, 3408 HIV serodiscordant couples from Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda and Zambia were enrolled in the Partners in Prevention HSV-2/HIV transmission study, a randomised, placebo-controlled, clinical trial of aciclovir as herpes simplex virus-2 (HSV-2) suppressive therapy for the prevention of HIV transmission. Aciclovir did not decrease HIV transmission risk within the couples.

Of the 3321 couples in the analysis, about a third (1085) included an HIV-positive male partner and the remaining two-thirds (2236) included an HIV-positive female partner. Eligibility included being over 18 years of age, having three or more episodes of vaginal intercourse in the three months before screening, and having the intention of remaining a couple.

HIV-positive partners were positive for HSV-2, had CD4 cell counts over 250 cells/mm3 and were not taking antiretrovirals. HIV-positive women pregnant at the time of screening were excluded from the study. Women who became pregnant stopped the study medication until the end of pregnancy. Pregnant HIV-negative women were included, as were those who became pregnant during follow-up.

HIV-positive partners were seen monthly, and HIV-negative partners were seen every three months. Sexual behaviour data including condom use was recorded at each visit, as was contraceptive use.

Comprehensive prevention services included individual and couple HIV-risk-reduction counselling, quarterly syndromic management of sexually transmitted infections, STI treatment and free condoms.

The majority were married and living together. Median CD4 cell count was 461 cells/mm3. The couples were followed for up to 24 months; median time for HIV-negative and HIV-positive partners was 20.9 months (IQR: 15.6-24.1) and 19.9 months (IQR: 14.3-23.9), respectively.

Of the 61 HIV seroconversions among women, close to 30% (17) happened during pregnancy. HIV incidence during pregnancy was 7.35 per 100 person years compared to 3.01 per 100 person years during non-pregnant periods,  (HR: 2.34, 95% CI: 1.33-4.09, p=0.003). Risk was high during both early and late pregnancy. However, in multivariate analysis after controlling for age, contraceptive use and unprotected sex, the effect of pregnancy on HIV risk was not statistically significant.

Of the 58 HIV transmissions to men, 12 (20.7%) happened during pregnancy. The incidence of female-to-male transmission was 3.46 per 100 person-years during pregnancy, compared to 1.58 per 100 person-years when the female partner was not pregnant. This was statistically significant  (HR  2.31, p=0.01) and remained significant after adjusting for confounding factors (HR.2.47, p=0.01).

The authors underscore the public health importance of these new findings showing pregnancy increases the risk of female-to-male transmission twofold. New strategies, they add, are needed “to strengthen family planning and maternal health services for women with and at risk for HIV in order to reduce unwanted pregnancies and avert HIV transmission to pregnant women and from pregnant women to their infants and partners”.

Strengths of the study include a large sample size and multinational cohort. The study also established a genetic viral linkage of transmitted HIV within partnerships, so minimising the potential for misclassification of female-to-male transmission.

The authors note their findings can be generalised; all participants were co-infected with HSV-2, as are over 80% of all HIV-positive adults in sub-Saharan Africa.

The authors conclude increased risk for HIV female-to-male transmission during pregnancy requires “further studies to understand the possible biologic mechanisms that may explain this finding”. They add: “Prenatal couples' HIV counselling and testing, implementation of repeat HIV testing in pregnancy, and earlier initiation of combination ART should become part of routine antenatal care to protect mothers, infants and male partners from HIV.”

References

Mugo NR et al. Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1 serodiscordant couples. Advance online edition of AIDS 25, doi: 10.1097/QAD.0b013e32834a9338, 2011.