Over 90% of maternal deaths and close to 90% of HIV transmission during birth or after delivery could be avoided using the World Health Organization’s (WHO) new criteria of when to start antiretroviral therapy, according to Louise Kuhn and colleagues in an analysis of a two year study of 1025 HIV-infected women and infants in Lusaka, Zambia published in the advance online edition of AIDS.
CD4 cell counts below 350 cells/mm³ proved the most useful measure to predict death and HIV transmission regardless of clinical stage.
WHO’s new guidelines in simplifying the criteria for starting ART have made it easier to identify those eligible for treatment. Treatment is now recommended for adults with either WHO clinical stage 3 or 4 HIV disease, regardless of CD4 cell count or those who have a CD4 count under 350 cells/mm³.
Previously those with a CD4 cell count under 350 cells/mm³ required a clinical disease stage 3 to be eligible.
Prevention of mother-to-child transmission (PMTCT) programmes play a significant role in identifying and treating HIV-infected adults. Treating HIV-infected women not only improves their life expectancy but is recognised as key to the health of their children as well as reducing the risks of HIV transmission.
The authors analysed data from a trial that took place in Lusaka, Zambia before antiretroviral treatment was widely available. 1025 HIV-positive women were recruited during pregnancy and followed for two years after having given birth. CD4 cell counts, viral load measurements and clinical stage were recorded at enrolment.
Children’s blood samples collected at birth, one week, one month and then monthly up to six months and then three-monthly up to 24 months were tested by polymerase chain reaction (PCR). Children were breastfed to four months with a median time of 12 months.
The authors looked at WHO criteria, both old and new, used to determine eligibility for treatment during pregnancy. They then reviewed the strength of these to predict deaths among women from delivery up to 24 months; perinatal transmission, that is detection of HIV infection before six weeks of age; and postnatal transmission, that is HIV infection after six weeks of age.
The authors found that 54% of women with a CD4 cell count below 350 cells/mm³ represented 88% of all deaths. Using the new treatment criteria of CD4 cell count and stage 3 clinical disease 68% were found to be eligible, representing 92% of all deaths.
While a viral load of 48,428 copies classified the same proportion of those eligible for treatment as a CD4 cell count below 350 cells/mm³, it only identified 76% of deaths. Viral load and CD4 count provide results similar to that of WHO’s new criteria. Adding viral load to new WHO criteria identified 96% of deaths requiring the treatment of 76%.
The authors warn against the suggestion of lowering CD4 cell thresholds in pregnant women due to anaemia in pregnancy (hemodilution). According to their calculations using CD4 cell count thresholds of 200, 250 and 300 cells/mm³ would identify only 59, 72 and 79% of deaths among women, respectively.
WHO’s new criteria would detect 88% of perinatal and postnatal infections whereas the old criteria and clinical disease stage detected in the region of 56% and 43-52%, respectively.
As the authors note viral load and CD4 cell count are independent predictors of HIV transmission. According to their data a combination of viral load and CD4 cell count as either/or criteria for starting antiretroviral treatment would provide better results than the new WHO criteria. Yet a slightly smaller proportion of women would be treated, 66.1% compared to 68.1%.
The authors add WHO’s new criteria could still prevent 82% of all infections even without extending treatment after delivery to those women who were not previously treatment-eligible. Cost per transmission averted is higher in this subset since the transmission rate is lower. Yet, they argue for extending treatment to this subset to further reduce transmission.
The authors note the addition of clinical staging marginally increased the numbers of women and infants at risk. They add that where laboratory testing is available and reliable, clinical staging in this context is of limited value.
The authors add that their “estimates of the proportion of deaths and infections averted are directly proportional to the proportion of the population meeting each criteria.” And as such, they note, the severity of the disease will differ locally, regionally and nationally dependent upon a number of factors including the stage of the disease, service provision and will vary over time.
The distribution of CD4 cell counts and clinical disease stage in their cohort, they add, was similar to a “large multi-site aggregation of data on pregnant women participating in the MTCT-Plus program in eight African countries.”
And they conclude: “Our data provide evidence-based support for the treatment thresholds in the revised WHO treatment guidelines. Our analysis also provides estimates of the large positive impact these guidelines could have if widely implemented on reducing mortality among women and HIV transmission to children.”
Kuhn L et al. Potential impact of new WHO criteria for antiretroviral treatment for prevention of mother-to-child transmission. AIDS, advance online publication, May 2010.