Van Schalkwyk M, Andersson MI, Zeier MD, La Grange Boccther M, Taljaard JJ, Theron GB. The impact of revised PMTCT guidelines: a view from a public sector antiretroviral clinic in Cape Town, South Africas. J Acquir Immune Defic Syndr. 2013 Jun 1;63(2):234-8.
To describe rates of mother-to-child HIV transmission (MTCT) before and after the implementation of new clinical guidelines for timing of antiretroviral therapy (ART) initiation.
A large infectious diseases clinic in Cape Town, South Africa.
Retrospective cohort study.
HIV-infected pregnant women initiating ART for their own health (i.e., not maternal antiretroviral prophylaxis against MTCT).
HIV transmission; loss to follow-up (LTFU).
Intervention (Predictor Variable)
Implementation of new guidelines recommending earlier ART initiation.
In April 2010, South Africa's National Department of Health released updated PMTCT guidelines advising ART initiation ≤2 weeks after diagnosis for all women with a CD4 count ≤350 cells/µL or WHO stage 3 or 4 disease.(1) The CD4 count threshold in the previous national guidelines had been ≤250 cells/µL.(2) Investigators reviewed data from all HIV-infected pregnant women initiating ART at the clinic during 2008, 2009 and 2010. Key indicators abstracted included baseline CD4 count, WHO clinical staging, co-morbidities, week of gestation, date of first antenatal clinic (ANC) visit, date of ART initiation, duration on ART before delivery, and duration on ART beforeloss to follow-up (LTFU). Neonatal outcome data were reviewed in regional databases for HIV testing results and infant HIV infection status.
Two hundred fifty women began ART over the study period (2008, n=82; 2009, n=71; 2010, n=97). There were no statistically significant differences in median age, parity or gestation at delivery. Baseline median CD4 counts at ART initiation were significantly higher in 2010 compared to 2009 (208 cells/µL, interquartile range [IQR] 138-270 cells/µL, vs. 157 cells/µL, IQR 104-206 cells/µL; p<0.001). Significantly fewer women presented with WHO stage 3 or 4 disease in 2010 than in 2009 (11/97, 11.3%, vs. 27/71, 23.9%; p=0.030). Median gestation at first ANC visit and at ART initiation were earlier in 2010 than in 2009 (ANC visit: 17 weeks, IQR 14-25 weeks, vs. 23 weeks, IQR 16-27 weeks; p=0.026; ART initiation: 25 weeks, IQR 21-31 weeks, vs. 30 weeks, IQR 26-34 weeks, p<0.001). More women received ART for eight or more weeks before delivery in 2010 than in 2009 (70/97, 73.7%. vs. n=32/71, 47.8%; p<0.001).
Two hundred fifty-six infants were born during the study period (2008, n=82; 2009, n=75; 2010, n=99). Polymerase chain reaction (PCR) test results were available for 212 (82.8%) infants overall, and the proportion for whom test results were available was higher in 2010 (90/99, 90.9%) than in 2009 (n=57/82, 76.0%). There were no cases of MTCT in 2010 (0, 0.0%), compared to four (7.0%) in 2009 and three (4.6%) in 2008. Infants had significantly higher odds of being infected if their mothers had been on ART for less than eight weeks before delivery (odds ratio [OR] 9.69, 95% confidence interval [CI] 1.66 to 56.58, p=0.017). There was no significant association between HIV transmission and maternal age, maternal parity, baseline CD4 count, WHO staging, baseline gestation or delivery method.
LTFU was very high throughout the study period, with 46 (18.4%) lost within 28 days of delivery and 94 (37.6%) within one year of initiating ART. Women initiating ART at =36 weeks gestation were significantly more likely to be lost within the first four weeks (7/27, 25.9%, vs. 23/223, 10.3%; p=0.028).
The authors conclude that following the release of the 2010 PMTCT guidelines, HIV-infected pregnant women began ART earlier in their pregnancies. The authors find that this longer period on ART before delivery is associated with a reduced risk of MTCT. They suggest that women should be educated about the benefits of entering care early and staying in care.
As a very small retrospective cohort study without an external comparator, risk of bias is moderate to high.
ART initiation at CD4 ≤350 cells/µL is associated with a greatly decreased risk of HIV transmission.(3) Malawi has implemented(4, 5) WHO's "Option B+,"(6) which advises that all HIV-infected pregnant and breastfeeding women begin lifelong ART regardless of CD4 count or clinical stage. If this approach can be implemented successfully in high-burden settings, rates of MTCT and other HIV transmission will likely decline very significantly. A key issue that will remain is getting patients into care early, and retaining them in care. Significant challenges may also exist in adapting health care models (e.g. through service integration and task-shifting) so that they can handle the greater numbers of women who will be in care.
Clinicians should follow WHO guidelines on PMTCT.
- South African National Department of Health. Clinical Guidelines: PMTCT (Prevention of Mother-to-Child Transmission). Pretoria: National Department of Health; 2010. [accessed 25 April 2013]
- South African National Department of Health. Policy and Guidelines for the Implementation of the PMTCT Programme. Pretoria: National Department of Health; 2008. [accessed 25 April 2013]
- Anglemyer A, Rutherford GW, Horvath T, Baggaley RC, Egger M, Siegfried N. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD009153.
- Centers for Disease Control and Prevention. Impact of an Innovative Approach to Prevent Mother-to-Child Transmission of HIV - Malawi, July 2011-September 2012. Morbidity and Mortality Weekly Report, March 1, 2013 / 62(08);148-151.
- Fasawe O, Avila C, Shaffer N, Schouten E, Chimbwandira F, et al. (2013) Cost-Effectiveness Analysis of Option B+ for HIV Prevention and Treatment of Mothers and Children in Malawi. PLoS ONE 8(3): e57778. doi:10.1371/journal.pone.0057778
- World Health Organization. Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. Geneva, Switzerland: World Health Organization; 2012. [accessed 9 May 2013]