Nineteen women (57%) started TB treatment and ART at the same visit. Nine women started TB treatment first [median 14 days (IQR: 10-25) before ART] and 5 started ART first [median 23 days (IQR: 14-315)]. Women who started ART first had a higher median CD4+ cell count at concurrent treatment initiation (387 cells/mm3) compared with women who started TB treatment first (75 cells/mm3) or both treatments concurrently (97 cells/mm3), but this difference did not reach statistical significance (P = 0.07). During pregnancy, 4 women (12.1%) had a single antiretroviral drug substitution.
Among 28 women with both an antepartum and postpartum CD4+ cell count all but 1 woman had a postpartum increase in CD4+ count, with a median increase of 104 cells per cubic millimeter (IQR: 56-235) at a median of 4 months postpartum (IQR: 3-6).
Of the 33 women, there was 1 maternal death. Her baseline CD4+ cell count was 6 cells per cubic millimeter, and she died of unknown causes at 24 weeks gestation after 6 weeks of concurrent treatment. One woman was lost to follow-up by 6 months postpartum. At the end of the data collection period, the remaining 31 women were alive and on ART.
Of 32 women who survived, 25 had known live births, 1 underwent a voluntary termination of pregnancy, 5 (15.2%) experienced pregnancy losses or stillbirths (3 in women who started ART and TB treatment concurrently and 2 in women who started ART first), and 1 infant outcome was unknown. In contrast, of the 1503 women in the MTCT-Plus Initiative who started ART alone (with no documented TB treatment) during pregnancy at a median gestational age of 30 weeks (IQR: 21-35) and with a median CD4+ count of 174 cells per cubic millimeter (IQR: 116-266), 88 women (5.9%) experienced a pregnancy loss or stillbirth.
Of the 25 live births, 1 infant was determined to be HIV infected, 20 were HIV negative, and 4 had an inconclusive HIV status. Of the latter 4, 1 child died at 2.5 months with 1 known negative HIV DNR PCR, but no confirmatory test, one died at 5 months with no results noted, and the other 2 voluntarily withdrew from the program at 5 months and 3.5 years of age with no HIV test results recorded.
We describe herein the clinical outcomes of a series of HIV-infected women who received TB treatment and ART concurrently during pregnancy. One of 33 women died during pregnancy, whereas 94% were alive and in care 6 months postpartum, with an overall median increase in CD4+ cell count of 104 cells per cubic millimeter. Concurrent treatment was generally well tolerated, with only 12.1% of women requiring single antiretroviral drug substitutions during pregnancy due to a medication side effect.
Pregnancy outcomes were less encouraging. The rate of pregnancy loss/stillbirth (15.2%) in this case series was more than twice that observed among women receiving ART alone during pregnancy in the MTCT-Plus Initiative. Similarly, in the observational arm of the Botswana Mma Bana study, the stillbirth rate among 170 women with a CD4+ cell count <200 cells per cubic millimeter who initiated ART during pregnancy was 6.5%.8 A number of factors may have contributed to the poor pregnancy outcomes observed in our case series. Not only did the women in this case series have more advanced HIV disease but they also had TB, both serious conditions requiring immediate treatment with multidrug regimens. Among the infants that survived, only 1 was determined to be HIV infected.
WHO guidelines for concurrent treatment of HIV and TB recommend efavirenz or abacavir as a substitute for nevirapine9 as pharmacokinetic drug-drug interactions between rifampin and nevirapine may lead to decreased plasma concentrations of nevirapine, with possible loss of antiretroviral efficacy. There was considerable heterogeneity in the ART regimens prescribed to women in this case series, with 33% receiving a nevirapine-containing regimen and another 33% receiving abacavir-containing regimens. Regardless of the ART regimen received, all but 1 woman experienced an increase in CD4+ cell count. However, postpartum hemoconcentration may have contributed to this observed increase.10
Our findings underscore the importance of early diagnosis and treatment of TB in HIV-infected pregnant women. Antenatal clinics with prevention of mother-to-child transmission programs are an important setting to implement active TB case finding. The feasibility of such an approach was demonstrated in 2 antenatal clinics in South Africa, where lay counselors used a TB symptom questionnaire to screen pregnant women for TB.11 They reported a TB prevalence rate among HIV-infected women enrolled in a prevention of mother-to-child transmission program of 2.2%, which is similar to the rate of 2.1% we found among women who received ART during pregnancy in the MTCT-Plus Initiative.
In summary, we found that concurrent treatment for TB and HIV infection during pregnancy is feasible and well tolerated, with good short-term maternal outcomes, although pregnancy losses and stillbirths were high. Further research is needed to determine the best practices for treating TB and HIV disease concurrently during pregnancy to improve maternal outcomes and ensure infant HIV-free survival.
The authors wish to thank the colleagues from the MTCT-Plus Initiative: ACONDA FSU and Abobo clinics, Cote d'Ivoire (Dr Siaka Toure); Cameroon Baptist Convention Clinics, Cameroon (Dr Pius Tih); Moi University College of Health Sciences Clinics, Kenya (Drs Robert Einterz and Joseph Mamlin); Nyanza Provincial General Hospital Clinic, Kenya (Dr Juliana Otieno); Beira and Chimoio Clinics, Mozambique (Health Alliance International); Treatment and Research AIDS Center, Rwanda (Dr Anita Assimwe); Cato Manor Clinic of UKZN, South Africa (Dr Anna Coutsoudous); Langa Health Clinic of Western Cape, South Africa (Dr Ivan Toms); Perinatal HIV Research Unit of University of Witswatersrand, South Africa (Dr James McIntyre); Thai Red Cross Clinic, Thailand (Dr Praphan Phanuphak); MU-JHU Cares Clinic, Uganda (Dr Philippa Musoke); St. Francis Hospital Clinic, Uganda (Dr Pius Okong); and Mtendere and Chelstone Health Clinics, Zambia (Dr Elizabeth Stringer).
Patricia L. Toro, MD, MPH*
Karen L. Schneider, PhD†
Rosalind J. Carter, PhD*
Elaine J. Abrams, MD*‡
Wafaa M. El-Sadr, MD, MPH*‡
Andrea A. Howard, MD, MS*
*International Center for AIDS Care and Treatment Programs (ICAP), Columbia University Mailman School of Public Health New York, NY
†John Snow, Inc, Boston, MA
‡Harlem Hospital, New York, NYHarlem Hospital and College of Physicians & Surgeons, Columbia University, New York, NY.
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