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Low Rates of Mother-to-Child HIV Transmission in Malawi
– Reported, June 13, 2013
Effective medical interventions for prevention of mother-to-child transmission of HIV (PMTCT) have been known since the early 1990s, and in developed countries, new pediatric HIV infections have become increasingly rare. Globally, in resource-limited settings, studies have demonstrated the efficacy or effectiveness of various PMTCT interventions, including single-dose nevirapine (sdNVP), combination prophylaxis, maternal antiretroviral treatment (ART), and extended infant prophylaxis. These studies have informed the development of World Health Organization (WHO) guidelines with simple and effective interventions that can result in transmission rates of less than 5% feasible, even in breastfeeding populations.
Despite these advances, an estimated 330,000 new infections occur in children every year, the vast majority attributed to vertical transmission. Persistent poor outcomes in developing countries generally are described as a result of HIV-infected mothers and exposed infants not receiving medical services. However, outside the unique environment of controlled research studies, few reports have documented the real-world effectiveness of PMTCT interventions when properly administered within routine programmatic settings.
Study results have been mixed regarding the relationship between immunosuppression and vertical transmission . In the context of appropriate PMTCT delivery that includes ART for eligible women, our results suggest that CD4+ cell count at the time of entry into PMTCT does not significantly impact transmission. In our cohort, those women at highest risk of transmitting the virus due to severe immunosuppression (<250 cells/mm3) had transmission rates that were not significantly different from those with less immunosuppression.
As expected, ART was more protective than was any other ARV regimen. Furthermore, starting ART at least 14 weeks prior to delivery (early ART) yielded the most benefit in reducing transmission, with no transmissions noted in the early ART group. These results are consistent with findings that complete viral suppression usually takes place after 12 to 16 weeks of therapy. Other clinical studies have reported similar results, including a study from Zambia that found that women who received ART for 4 or fewer weeks had a 5.5- fold increased odds of transmission when compared with women on HAART for at least 13 weeks. Similarly, all women enrolled in the Dream Program in Malawi, Tanzania, and Mozambique were started on ART at 25 weeks and were found to have a transmission rate of just 0.81.2% at 1 month. Importantly, over one third of the women in our cohort who were on ART received it for fewer than 14 weeks prior to delivery (i.e., less than the optimal longer duration). Moreover, over one-third of our cohort was enrolled during the third trimester. Therefore, our results not only confirm that early initiation of ART yields maximal benefits in reducing transmission but also highlight that increasing efforts need to be made to ensure that women present to antenatal care sooner and early initiation of ART be a priority PMTCT intervention.
However, an important note is that option B+ in Malawi uses an efavirenz (EFV)-based ART regimen, as compared to the NVP based treatment regimen used in our cohort. The potential risk of rare EFV related teratogenicity in the first trimester needs ongoing monitoring, especially given the number of HIV-infected women who may have repeat pregnancies while on EFV. This potential risk also further highlights the need for family planning services to be included and prioritized with roll out of option B+.
Despite support for early ART initiation and option B+, the efficacy of this approach will be compromised unless efforts are made to promptly link newly identified women to ART services and to ensure identification, enrollment into care, and testing of exposed infants.
These results provide reassurance that low HIV transmission rates can be achieved even in resource-limited settings. Maximum benefit is received from ART started at least 14 weeks prior to delivery for eligible women versus other regimens. Furthermore, more advanced HIV disease as indicated by lower baseline CD4+ cell count does not impact transmission among women in the setting of appropriate provision of maternal ART and PMTCT prophylaxis. Improving timely initiation of ART and PMTCT prophylaxis is essential to effectively reduce MTCT of HIV on a global scale.
CREDITS.
http://www.ncbi.nlm.nih.gov/
Maria H. Kim, Saeed Ahmed, Geoffrey A. Preidis, Elaine J. Abrams, Mina C. Hosseinipour, Thomas P. Giordano, Elizabeth Y. Chiao, Mary E. Paul, Avni Bhalakia, Debora Nanthuru, and Peter N. Kazembe
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