Zambian study shows importance of early HIV test and fast ART for pregnant women

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Starting ART at least 13 weeks before giving birth provides the greatest benefits in prevention of mother-to-child transmission (PMTCT), Carla J Chibwesha and colleagues reported in a retrospective cohort analysis of pregnant HIV-infected women attending public antenatal care clinics in Lusaka, Zambia published in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

Women who got ART for a month or less before giving birth had more than a five-fold increased risk of transmitting HIV to their infants compared to women on ART for at least 13 weeks (95% CI: 2.5-11). 

The findings underline the importance of HIV counselling and testing at the earliest opportunity after a woman becomes pregnat, and the importance of minimising the delay between testing positive and starting antiretroviral treatment.

Glossary

antenatal

The period of time from conception up to birth.

perinatal

Relating to the period around the time of birth. Perinatal transmission is when HIV is passed on during pregnancy, childbirth or breastfeeding. People with perinatally-acquired HIV have been living with HIV since birth or infancy.

perinatal

Relating to the period starting a few weeks before birth and including the birth and a few weeks after birth.

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.

inter-quartile range

The spread of values, from the smallest to the largest. The inter-quartile range (IQR) only includes the middle 50% of values and measures the degree of spread of the most common values.

Over 90% of the more than 1,000 daily new paediatric HIV infections are in sub-Saharan Africa. Maternal ART can reduce MTCT to 2-5% or lower.

While the World Health Organization (WHO) guidelines now recommend that all pregnant women with CD4 cell counts under 350 cells/mm3 should start ART, women in resource-poor settings are usually restricted to four or fewer antenatal visits, which means that HIV testing may take place late in pregnancy, delaying the start of treatment until the third trimester.

Maternal viral load for women on ART during pregnancy and breastfeeding determines the risk of transmission, so suppression of viral load is the primary goal of ART for PMTCT. Viral load monitoring can help guide clinical management during pregnancy. However, for financial and logistic reasons, this option is rarely available in resource-poor settings.

While guidelines recommend starting ART as soon as a woman is eligible, the optimal time on antenatal ART is unclear.

The authors undertook a retrospective cohort analysis to look at the effect of the duration of antenatal ART on perinatal HIV transmission. Women who began ART before or during pregnancy and whose infants had had an HIV polymerase chain reaction (PCR) test between three and 12 weeks of life were included.

In Lusaka routine HIV testing in antenatal clinics has resulted in a testing rate of over 90% for women. CD4 cell counts are routinely done for ART eligibility. Women get ART in treatment centres or in antenatal clinics with integrated ART services.

Comprehensive medical information on mothers and newborns up to six weeks of age has been collected in the public antenatal clinics since 2006 through an electronic medical record system.

Length of ART treatment was classified as: four weeks or less; 5-8 weeks; 9-12 weeks, or 13 weeks or more.

From January 2007 to March 2010 of the 1813 HIV-infected pregnant included in the analysis the overall mother-to-child transmission rate was a relatively low 3.3% (59 of 1,813) (95% CI: 2.5-4.2%) between three and 12 weeks of life.

The mean age was 29 years. Over 90% of the women were married with more than 85% pregnant previously.  At the first antenatal visit the mean gestational age was 21 weeks (standard deviation ± six weeks).The median CD4 cell count was 231 cells/mm3(IQR: 164-329 cells/mm3) and median length of time on ART before giving birth was 13 weeks (IQR: 8-19 weeks).

Length of time on treatment before delivery was the most important predictor of perinatal transmission.

As in a previous study a positive syphilis test during pregnancy was found to be an independent risk factor for perinatal transmission (AOR 3.8; 95% CI: 1.3-10.7).

A generalised additive model suggested limited protective benefits beyond 13 weeks on ART. 

An exploratory analysis of women on ART for less than 13 weeks showed that for each additional week on ART before giving birth the risks of perinatal transmission were reduced by 14% (OR: 0.86; 95% CI: 0.77-0.96).

Most women, the authors note, present for antenatal care in the second trimester allowing sufficient time to start ART. A lack of timely identification of HIV-infected pregnant women and subsequent linking to services results in poor standards of care and preventable perinatal HIV infections.

Their findings, the authors note, underline the critical importance of getting pregnant women into antenatal care early and for providers to determine ART eligibility and start treatment promptly.

The authors suggest key components for programme success include:  support of routine HIV counselling and testing; improved clinical and laboratory services including point of care CD4 cell counts; integration of ART services into antenatal clinic settings and credentialing nurses and midwives to prescribe ART (task shifting).

Enhanced antenatal care that promotes the prevention, screening and treating of preventable conditions including sexually transmitted infections and anaemia may improve women’s health and decrease perinatal HIV transmission, they add.

Strengths of the study include a large sample size and robust electronic medical record system.

As in most resource-poor settings routine ultrasound to determine age of the foetus and plasma viral load data were not available so limiting the findings.

In the absence of viral load monitoring to guide HIV management the authors recommend pregnant women with CD4 cell counts under 350 cells/mm3 start ART at least four weeks but preferably 13 weeks before delivery to ensure the greatest chance of preventing vertical transmission.

References

Chibwesha CJ et al. Optimal time on HAART for prevention of mother-to-child transmission of HIV. Advance online edition of JAIDS doi: 10.1097/QAI.0b013e318229147e, 2011.