Missed opportunities for HIV testing of pregnant women

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Kenyan women are becoming infected with HIV during pregnancy at very high rates, and repeat testing prior to delivery, or at the earliest possible opportunity after birth, should be encouraged in order to reduce mother-to-child transmission, Kenyan researchers reported last week at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.

When mothers who tested negative before giving birth were retested six weeks after having given birth at six health clinics in Nairobi and Western Kenya, they showed a significant HIV incidence.

Women in Western Kenya, where the HIV prevalence rate of 15% is over twice the national rate, were at especially high risk for seroconversion during pregnancy.

Glossary

seroconversion

The transition period from infection with HIV to the detectable presence of HIV antibodies in the blood. When seroconversion occurs (usually within a few weeks of infection), the result of an HIV antibody test changes from HIV negative to HIV positive. Seroconversion may be accompanied with flu-like symptoms.

 

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

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.

middle income countries

The World Bank classifies countries according to their income: low, lower-middle, upper-middle and high. There are around 50 lower-middle income countries (mostly in Africa and Asia) and around 60 upper-middle income countries (in Africa, Eastern Europe, Asia, Latin America and the Caribbean).

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

Prevention of mother-to-child transmission (PMTCT) programmes have focused primarily on preventing transmission from an HIV-infected woman to her infant. Little attention has been given to the other key elements of a globally recognised comprehensive strategy that includes prevention of HIV in women and prevention of unwanted pregnancies, as well as care and treatment for the HIV-infected woman and her family.

An estimated 1.4 million pregnant women in low- and middle-income countries are living with HIV, of which 90% are in sub-Saharan Africa. Only an estimated 21% of pregnant women received an HIV test in 2008 and 45% received drugs to prevent mother-to-child transmission.

Most of the women who attend PMTCT programmes are HIV negative. Yet evidence suggests that there is a high incidence of HIV infection during pregnancy and the immediate period after having given birth. Identifying co-factors for HIV infection during this time will help develop needed strategies to reduce the rate of seroconversion.

Mothers who brought their infants for routine childhood immunisations at six maternal-child clinics in Nairobi and Western Kenya were offered HIV testing. Questionnaires were completed before testing.

HIV-negative mothers who tested positive were compared with those who did not seroconvert.

2035 women (95.3%) who had tested negative before giving birth agreed to be re-tested. Fifty-three (2.6%) tested positive with an estimated HIV incidence rate of 6.8 per 100 woman years (95% CI: 5.1-8.8). The incidence rate was considerably higher in Western Kenya than in the capital Nairobi (13.8 per 100 women years, 95% CI 9.6-18.9 versus 3.9 per 100 women years, 95% CI 2.4-5.8). Being employed (45.3% versus 29.0% p = 0.01), married and from a high-prevalence region increased the likelihood of seroconversion.

For married women in a polygamous relationship the possibility for seroconversion increased significantly (19.6% versus 6.7%, p < 0.001).

In a multivariate analysis both region (OR: 3.6 95% CI: 2.1-6.4) and being employed (OR 1.9 95% CI:1.1-3.3) were independent predictors of seroconversion.

The researchers highlighted the limitations of the study that included no data on the timing of the first HIV test and no data on the partner’s HIV status.

Acceptance of repeat early testing following birth is high and resulted in significant rates of HIV incidence. The findings of high HIV incidence among women who had participated in PMTCT programmes supports the need for “urgent review of services provided to HIV uninfected women”, said John Kinuthia of Kenyatta National Hospital, Nairobi, presenting the findings.

He noted that the HIV incidence seen in pregnant women in this study was as high as in cohorts of sex workers, indicating that pregnant women are a high-risk group for serconversion.

“Preventing incident infection during pregnancy is critical because of the high viral load associated with primary HIV infection,” he went on.

PMTCT interventions need to address HIV-negative as well as HIV-positive women, he explained, and should not assume that because a woman tests HIV-negative, no risk of HIV transmission exists.

In particular there is a need for couples counselling, and where women test alone it is important to encourage her partner to be tested, he said. Where women test HIV-negative, partner testing remains important because it may identify women in discordant relationships, while counselling may expose other risk factors that need to be addressed.

A second study, carried out in Swaziland, showed that where repeat testing can be implemented during labour or delivery, it results in increased use of antiretroviral prophylaxis.

Mary Pat Kieffer of the Elisabeth Glaser Pediatric Foundation (EGPAF) reported on an intervention in Swaziland designed to increase uptake of antiretroviral prophylaxis through a number of measures:

  • Provision of HIV testing and counselling to all women who arrived at maternity services with unknown HIV status.
  • Offer of nevirapine prophylaxis to all women who declined an HIV test.
  • Routine re-testing for HIV of all women who had tested negative more than three months prior to delivery.
  • Ensuring that all women with HIV, known or newly diagnosed, took ARV prophylaxis as prescribed.

Maternity nurses received a one-day training to ensure that they understood their roles, and the actions they needed to take, to ensure these outcomes. The effectiveness of the intervention was evaluated through a study of six EGPAF-supported maternity units, which were randomised to receive the intervention or act as control sites.

The primary outcome of interest in the study was the percentage of infant cord blood samples which were HIV-positive and contained nevirapine, as an indicator of the proportion of women with HIV who had been reached with antiretroviral prophylaxis at the time of delivery.

Nevirapine was used as a surrogate for antiretroviral prophylaxis, which might consist of either AZT/3TC/nevirapine or short-course AZT/3TC plus single dose nevirapine and a post-delivery `tail` of AZT/3TC, according to whether the mother qualified for antiretroviral treatment under Swazi guidelines.

The study enrolled 2444 women, of whom 2211 had undergone HIV testing previously (91%). A further 215 women had an unknown HIV status at the time they arrived at the maternity clinic to give birth.

Analysis of cord blood samples (2386 samples) showed that HIV-positive women who attended intervention clinics were significantly more likely to have taken nevirapine (80% vs 69%, p = 0.0001).

When the results were broken down by HIV status on arrival at the maternity clinic, it was clear that women who had not already been diagnosed prior to their delivery were much less likely to have taken nevirapine.

However, women attending the intervention clinics had a significantly higher frequency of detectable nevirapine, regardless of whether they were already known to be positive, diagnosed at the maternity clinic or with unknown HIV status at the time of delivery.

HIV incidence among pregnant women was extremely high, at 16.75 seroconversions per 100 person-years. In comparison, noted the presenter, incidence among pregnant women in the Rakai population study, reported in 2005, was 2.3 per 100 person-years, while incidence among non-pregnant women was 1.1 per 100 person-years in that study.

ARV provision to women who seroconverted during pregnancy doubled at the intervention sites (54% vs 26%, p = 0.03).

The proportion of HIV-negative women retested in maternity clinics was significantly greater in intervention clinics, but still low, due to Swazi guidelines which recommend that repeat testing should take place at least 90 days after a previous negative test. (14% at control sites vs 45% at intervention sites, p = 0.0001). Thirty-eight per cent who seroconverted had been tested less than 90 days before delivery, and so were not re-tested.

Reaching women who are infected late in pregnancy should not be an afterthought for PMTCT programmes, said Kieffer.

In the discussion following the presentation, there was controversy over whether the higher rates of seroconversion in pregnant women were due to biological or behavioural vulnerability. At present there is no evidence that pregnancy increases a woman’s biological vulnerability to infection, but behavioural factors may contribute to the high rate of seronversion seen in various populations of pregnant women.

“Part of the behavioural risk that we’re finding in Swaziland is that when women are pregnant, they are considered safe to have sex with,” said Keiffer.

Further information

You can view abstract 156 and abstract 155 on the official conference website.

You can also view a webcast and slides of this session on the official conference website.

References

Kieffer MP et al. Repeat HIV testing in labor and delivery as a standard of care increases ARV provision for women who seroconvert during pregnancy. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 156, 2010.

Kinuthia J et al. Co-factors for HIV incidence during pregnancy and the postpartum period. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 155, 2010.