Optimal time on HAART for prevention of mother-to-child transmission of HIV

Abstract

To determine the impact of time between initiating highly active antiretroviral therapy (HAART) and delivery-duration of antenatal HAART-on perinatal HIV infection.
We conducted a retrospective cohort analysis of pregnant HIV-infected women in Lusaka, Zambia. Women in our cohort were receiving HAART and had an infant HIV polymerase chain reaction test between 3 and 12 weeks of life.
We examined factors associated with infant HIV infection and performed a locally weighted regression analysis to examine the effect of duration of antenatal HAART on perinatal HIV infection.
: From January 2007 to March 2010, 1813 HIV-infected pregnant women met inclusion criteria. Mean gestational age at first antenatal visit was 21 weeks (SD ± 6), median CD4+ cell count was 231 cells per microliter (interquartile range: 164-329), and median duration of antenatal HAART was 13 weeks (interquartile range 8-19). Fifty-nine (3.3%) infants were HIV infected. Duration of antenatal HAART was the most important predictor of perinatal HIV transmission. Compared with women initiating HAART at least 13 weeks before delivery, women on HAART for ≤4 weeks had a 5.5-fold increased odds of HIV transmission (95% confidence interval: 2.6 to 11.7). Locally weighted regression analysis suggested limited additional prophylactic benefit beyond 13 weeks on antenatal HAART.
Low rates of mother-to-child HIV transmission can be achieved within programmatic settings in Africa. Maximal effectiveness of prevention of mother-to-child transmission programs is achieved by initiating HAART at least 13 weeks before delivery.

Full text

Optimal Time on HAART for Prevention of Mother-to-Child
Transmission of HIV
Carla J. CHIBWESHA, MD, MSc1,2, Mark J. GIGANTI, MS1,2, Nande PUTTA, MBChB, MPH2,
Namwinga CHINTU, MBChB, MMed2, Jessica MULINDWA, MBChB2,3, Benjamin J.
DORTON, BS2, Benjamin H. CHI, MD, MSc1,2, Jeffrey S. A. STRINGER, MD1,2, and Elizabeth
M. STRINGER, MD, MSc1,2
1University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
2Centre for Infectious Disease Research in Zambia, Lusaka, Zambia
3University Teaching Hospital, Lusaka, Zambia
Abstract
Objectives—To determine the impact of time between initiating highly active antiretroviral
therapy (HAART) and delivery – duration of antenatal HAART – on perinatal HIV infection.
Design—We conducted a retrospective cohort analysis of pregnant HIV-infected women in
Lusaka, Zambia. Women in our cohort were receiving HAART and had an infant HIV polymerase
chain reaction (PCR) test between 3 and 12 weeks of life.
Methods—We examined factors associated with infant HIV infection and performed a locally
weighted regression analysis to examine the effect of duration of antenatal HAART on perinatal
HIV infection.
Results—From January 2007 to March 2010, 1,813 HIV-infected pregnant women met inclusion
criteria. Mean gestational age at first antenatal visit was 21 weeks (standard deviation (SD)+/−6),
median CD4+ cell count was 231 cells/uL (interquartile range (IQR) 164 – 329), and median
duration of antenatal HAART was 13 weeks (IQR 8 – 19). 59 (3.3%) infants were HIV-infected.
Duration of antenatal HAART was the most important predictor of perinatal HIV transmission.
Compared to women initiating HAART at least 13 weeks prior to delivery, women on HAART for
≤ 4 weeks had a 5.2-fold increased odds of HIV transmission (95% confidence interval (CI): 2.5 –
11.0). Locally weighted regression analysis suggested limited additional prophylactic benefit
beyond 13 weeks on antenatal HAART.
Conclusions—Low rates of mother-to-child HIV transmission can be achieved within
programmatic settings in Africa. Maximal effectiveness of prevention of mother-to-child
transmission (PMTCT) programs is achieved by initiating HAART at least 13 weeks prior to
delivery.
Keywords
HIV; prevention of mother-to-child transmission; highly active antiretroviral therapy; pregnancy
CORRESPONDING AUTHOR: Carla Chibwesha, MD, MSc, Centre for Infectious Disease Research in Zambia, PO Box 34618,
Lusaka, Zambia, Carla.Chibwesha@cidrz.org, Tel: +260.976.379.677, Fax: +260.211.293.766.
REQUEST FOR REPRINTS: Carla Chibwesha, MD, MSc, Centre for Infectious Disease Research in Zambia, PO Box 34618,
Lusaka, Zambia, Carla.Chibwesha@cidrz.org, Tel: +260.976.379.677, Fax: +260.211.293.766
DISCLOSURE: The authors have no financial interests to disclose. Data presented in this manuscript were presented, in part, at the
XVIIIth International AIDS Conference and published as abstract MOPE0261.
NIH Public Access
Author Manuscript
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.
Published in final edited form as:
J Acquir Immune Defic Syndr
. 2011 October 1; 58(2): 224–228. doi:10.1097/QAI.0b013e318229147e.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

INTRODUCTION
Of the more than 400,000 new pediatric HIV infections reported in 2008, the majority
occurred in sub-Saharan Africa [1]. Maternal prophylaxis with highly active antiretroviral
therapy (HAART) has been shown to dramatically reduce the risk of mother-to-child HIV
transmission even if a woman chooses to breastfeed [2–5]. Current World Health
Organization (WHO) guidelines recommend that all pregnant women whose CD4+ count is
< 350 cells/uL commence HAART. In resource-limited settings, identification of mothers
who are candidates for HAART and/or prophylaxis to prevent mother-to-child HIV
transmission must typically be achieved within four or fewer antenatal care visits. However,
the complexity of the PMTCT cascade – from identification of HIV-infected pregnant
women to initiation of antiretroviral prophylaxis or treatment – often results in missed
opportunities for intervention [6, 7].
For women receiving HAART during pregnancy and the breastfeeding period, maternal HIV
viral load is among the most important predictors of perinatal transmission risk [8, 9]. Viral
suppression is thus a central goal of antiretroviral therapy for PMTCT. Where available,
HIV viral load monitoring is used to guide clinical management during pregnancy and to
inform recommendations regarding mode of delivery. In sub-Saharan African settings, viral
load monitoring is not commonly available as these assays are costly and require well-
established laboratory infrastructure [10].
Although the common clinical practice is to start HAART in pregnancy as soon as a woman
is determined to be eligible for therapy, the threshold duration of antenatal HAART required
for maximal PMTCT benefit remains unclear. A European Collaborative Study showed that
93.4% (95% CI 66.0 – 99.0) of women receiving nevirapine-containing HAART achieved
viral suppression by 15 weeks [11]. A subsequent study of South African women initiating
HAART during pregnancy demonstrated that each additional week of treatment reduced the
odds of perinatal HIV transmission by 8% [12]. These findings are similar to previously
reported data from a French Perinatal Cohort in which a 6% reduction in the odds of
perinatal HIV transmission was reported for each additional week of treatment with HAART
during pregnancies delivered at term [13]. We report the findings of a retrospective cohort
analysis in which we investigated the optimal time at which HAART should be initiated in
pregnancy to maximize PMTCT effectiveness.
METHODS
We conducted a retrospective cohort analysis of pregnant HIV-infected women attending
public antenatal care clinics in Lusaka, Zambia. Routine HIV screening is performed in
antenatal clinics and the district’s “opt-out” HIV testing policy has resulted in over 90% of
women being screened for HIV in recent years [14]. In addition, CD4+ cell counts are
routinely obtained on HIV-infected pregnant women to assess eligibility for maternal
HAART [15]. Pregnant women receive HAART either in HIV treatment clinics or in
antenatal clinics with integrated antiretroviral treatment (ART) services. An electronic
medical record system, the Zambia Electronic Perinatal Record System (ZEPRS), has been
in use in Lusaka’s public antenatal care clinics since 2006 and collects comprehensive
medical information on mothers and newborns up to 6 weeks of age.
Women who began HAART either prior to or during pregnancy were eligible for inclusion
in this analysis. However, we restricted inclusion in the analysis to those women on HAART
whose infant had been PCR tested between 3 and 12 weeks of life. In the case of multiple
gestation, we restricted our analysis to the first-born child. We ascertained obstetric history,
gestational age at initiation of antenatal care, results of lab tests (hemoglobin, syphilis, and
CHIBWESHA et al. Page 2
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

CD4+ cell count), gestational age at delivery, and infant birth weight through review of
ZEPRS records. Gestational age was calculated by last menstrual period for pregnancies less
than 20 weeks at time of enrollment into antenatal care. For those at or over 20 weeks at
enrollment, both last menstrual period and symphysis-fundal height were used. If these two
methods yielded gestational ages within three weeks of each other, the date based on the last
menstrual period was used. If not, the fundal height-derived gestational age was used. Dates
of HAART initiation were also determined through ZEPRS review. We categorized duration
on HAART as being ≤ 4 weeks, 5 – 8 weeks, 9 – 12 weeks, or ≥ 13 weeks.
Our primary outcome was infant HIV infection, assessed by PCR performed on dried blood
spots using the Abbott M2000 assay (Abbott Laboratories, Abbott Park, Illinois). We
investigated predictors of mother-to-child HIV transmission in separate logistic regression
models. In addition to maternal age and infant weight at delivery, variables for maternal
characteristics statistically significant in univariable analyses (p ≤ 0.05) were included in a
multivariable logistical regression model. In addition, we used a generalized additive model
with a locally weighted regression to graphically depict the relationship between duration of
antenatal HAART and HIV transmission. This analysis was restricted to women who
initiated HAART during pregnancy. All statistical analyses were performed using SAS
version 9.1.3 (SAS Institute Inc, Cary, North Carolina). Ethical approval for this analysis of
routinely collected clinical data was obtained from the University of Zambia Biomedical
Research Ethics Committee (Lusaka, Zambia) and the University of Alabama at
Birmingham Institutional Review Board (Birmingham, AL, USA).
RESULTS
Between January 2007 and March 2010, 4,254 live births in Lusaka district clinics were
recorded among HIV-infected mothers on HAART. 1,813 mother-infant pairs had early
infant diagnosis HIV PCR results documented and met inclusion criteria for this analysis.
The mean age was 29 years (SD +/− 5 years) and nearly half of the women (48.4%) had
completed some secondary or tertiary education. Most women in our cohort were married
(93.4%) and had previously been pregnant (85.7%). The mean gestational age at first
antenatal care visits was 21 weeks (SD +/− 6 weeks). The mean hemoglobin result was 11.0
g/dL (SD +/− 1.6 g/dL) and 72.6% of women had a negative syphilis screen at their first
antenatal visit. Approximately half (52.8%) of the women in our cohort had a CD4+ count <
350 cells/uL at entry into antenatal care (Table 1).
59 of 1,813 (3.3%; 95% CI 2.5 – 4.2%) infants were HIV-infected at the time of their
earliest PCR result (3 – 12 weeks of life). In univariable analysis, the odds of HIV
transmission were elevated among women with unknown educational status (odds ratio
(OR) 2.3; 95% CI 1.1 – 4.8), hemoglobin concentration ≤ 8.0 – 9.9 g/dL (OR 2.5; 95% CI
1.2 – 5.0), CD4+ cell count <200 cells/uL (OR 3.5; 95% CI 1.2 – 10.2), and those who
screened positive for syphilis (OR 4.4; 95% CI 1.7 – 11.9). Additionally, the odds of
mother-to-child HIV transmission was markedly elevated among women who had initiated
HAART four or fewer weeks prior to delivery compared to women who had initiated
HAART at least 13 weeks prior to delivery (OR 4.3; 95% CI 2.3 – 8.1).
In multivariable analysis, a short duration of antenatal HAART (i.e., ≤ 4 weeks) compared
to an interval of at least 13 weeks (adjusted odds ratio (AOR) 5.2; 95% CI 2.6 – 11.7) and a
positive syphilis screen compared to a negative one (AOR 3.8; 95% CI 1.3 – 10.7) remained
associated with higher odds of mother-to-child HIV transmission. We also observed a trend
towards increased odds of mother-to-child HIV transmission among women starting
HAART 5 – 8 weeks prior to delivery (AOR 2.0; 95% CI 0.8 – 5.1) and 9 – 12 weeks prior
to delivery (AOR 1.8; 95% CI 0.7 – 4.8). However, this trend was not statistically
CHIBWESHA et al. Page 3
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

significant. A locally weighted regression line generated with a generalized additive model
suggested limited additional benefit beyond 13 weeks on HAART during the antenatal
period (Figure 1). An exploratory analysis limited to women on HAART for fewer than 13
weeks demonstrated that for each additional week on HAART prior to delivery the odds of
mother-to-child HIV transmission were reduced by 14% (OR 0.86; 95% CI 0.77 – 0.96).
DISCUSSION
In this cohort analysis of women on antenatal HAART, we observed an encouragingly low
overall mother-to-child HIV transmission rate of 3.3% (95% CI 2.5 – 4.2%) between 3 and
12 weeks of life. The most important predictor of vertical HIV transmission in this cohort
was time on HAART prior to delivery. Women who received HAART for four or fewer
weeks during pregnancy had a 5.2-fold increased odds of transmitting HIV to their infants
compared to women on HAART for at least 13 weeks. A positive syphilis screen during
pregnancy was also found to be an independent risk factor for mother-to-child HIV
transmission (AOR 3.8; 95% CI 1.3 – 10.7). This association is consistent with findings
previously reported in a Malawian PMTCT study in which the risk of perinatal HIV
transmission was 2 – 3 times higher among women diagnosed with syphilis [16].
The Zambia Exclusive Breastfeeding Study demonstrated that nearly 70% of HIV-infected
women enrolled in antenatal care in Lusaka meet current criteria for initiation of HAART
[17, 18]. In many developing country settings, women commonly present for antenatal care
in the second trimester, which would allow adequate time for initiation of HAART.
However, delays in CD4+ cell triage and in linking HIV-infected mothers with PMTCT and
HIV treatment services commonly result in suboptimal prophylaxis and preventable
perinatal HIV infections [19]. Our study highlights the importance of encouraging women to
seek antenatal care early in pregnancy and instilling a sense of urgency in providers to
determine eligibility for HAART and initiate treatment in a timely manner. Design and
implementation of programs that support routine HIV counseling and testing (e.g., “opt-out”
testing) [20, 21] and improvements in clinical and laboratory services are critically
important for program success. Additional strategies to improve management of HIV-
infection in pregnancy and reduce perinatal HIV transmission may include point of care
CD4+ cell counts [22], integration of ART services into antenatal clinic settings, and
credentialing non-physician providers (such as nurses or midwives) to prescribe HAART
[23–25]. Enhancing antenatal care services, promoting prevention, screening, and treatment
of preventable conditions such as syphilis and anemia could also improve women’s health
and decrease perinatal HIV transmissions.
The strengths of our study include its large sample size and use of a robust electronic
medical record. Our results are limited by the absence of routine ultrasonography confirming
gestational age and routine data on plasma viral load, neither of which is widely available in
Zambia. Where accessible, viral load monitoring may be used to guide HIV management
and decisions regarding mode of delivery in order to further minimize risk of vertical HIV
transmission. However, in the common circumstances where viral load monitoring is neither
readily available nor affordable, pregnant women should initiate HAART at least 4 weeks
prior to delivery to optimally reduce mother-to-child HIV transmission.
Our study confirms that, in the era of HAART, rates of perinatal HIV transmission below
5% can be achieved in African settings. In order to maximize PMTCT effectiveness,
however, women eligible for HAART should receive at least 4 weeks – and preferably 13
weeks – of treatment prior delivery. To achieve this, PMTCT and ART services will need to
be substantially improved and expanded.
CHIBWESHA et al. Page 4
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

Acknowledgments
FUNDING: Trainee support was provided by the National Institutes of Health through the International Clinical
Research Fellows Program at Vanderbilt University (R24 TW007988) and the Vanderbilt-CIDRZ AIDS
International Research and Training Program (D43 TW001035). Additional investigator salary was provided
through a Clinical Scientist Development Award from the Doris Duke Charitable Foundation (2007061). Funding
agencies played no role in study design, data collection, data analysis, or manuscript preparation.
CJC designed and interpreted the analysis, drafted the manuscript, and substantially revised it. MJG analyzed study
data, interpreted the analysis, and substantially revised the manuscript. NP, NC, JM, and BJD participated in data
interpretation and manuscript revision. BHC, JSAS, and EMS designed the analysis, interpreted the analysis, and
substantially revised the manuscript. We thank Jessica Joseph for her assistance in preparing this manuscript.
Trainee support was provided by the National Institutes of Health through the International Clinical Research
Fellows Program at Vanderbilt University (R24 TW007988) and the Vanderbilt-CIDRZ AIDS International
Research and Training Program (D43 TW001035). Additional investigator salary was provided through a Clinical
Scientist Development Award from the Doris Duke Charitable Foundation (2007061).
References
1. WHO. Global Summary of the HIV/AIDS Epidemic. 2008.
2. Palombi L, Marazzi MC, Voetberg A, Magid NA. Treatment acceleration program and the
experience of the DREAM program in prevention of mother-to-child transmission of HIV. AIDS.
2007; 21 (Suppl 4):S65–71. [PubMed: 17620755]
3. Kilewo C, Karlsson K, Ngarina M, Massawe A, Lyamuya E, Swai A, et al. Prevention of mother-to-
child transmission of HIV-1 through breastfeeding by treating mothers with triple antiretroviral
therapy in Dar es Salaam, Tanzania: the Mitra Plus study. J Acquir Immune Defic Syndr. 2009;
52:406–416. [PubMed: 19730269]
4. Chasela CS, Hudgens MG, Jamieson DJ, Kayira D, Hosseinipour MC, Kourtis AP, et al. Maternal
or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med. 2010; 362:2271–2281.
[PubMed: 20554982]
5. McIntyre J. Use of antiretrovirals during pregnancy and breastfeeding in low-income and middle-
income countries. Curr Opin HIV AIDS. 2010; 5:48–53. [PubMed: 20046147]
6. Mnyani CN, McIntyre JA. Preventing mother-to-child transmission of HIV. BJOG. 2009; 116
(Suppl 1):71–76. [PubMed: 19740178]
7. Stringer EM, Ekouevi DK, Coetzee D, Tih PM, Creek TL, Stinson K, et al. Coverage of Nevirapine-
Based Services to Prevent Mother-to-Child HIV Transmission in 4 African Countries. JAMA. 2010;
304:293–302. [PubMed: 20639563]
8. Taha TE, Hoover DR, Kumwenda NI, Fiscus SA, Kafulafula G, Nkhoma C, et al. Late postnatal
transmission of HIV-1 and associated factors. The Journal of infectious diseases. 2007; 196:10–14.
[PubMed: 17538877]
9. Mmiro FA, Aizire J, Mwatha AK, Eshleman SH, Donnell D, Fowler MG, et al. Predictors of early
and late mother-to-child transmission of HIV in a breastfeeding population: HIV Network for
Prevention Trials 012 experience, Kampala, Uganda. J Acquir Immune Defic Syndr. 2009; 52:32–
39. [PubMed: 19617849]
10. Mepham SO, Bland RM, Newell ML. Prevention of mother-to-child transmission of HIV in
resource-rich and -poor settings. BJOG : an international journal of obstetrics and gynaecology.
2011; 118:202–218. [PubMed: 21040391]
11. Patel D, Cortina-Borja M, Thorne C, Newell ML. Time to undetectable viral load after highly
active antiretroviral therapy initiation among HIV-infected pregnant women. Clin Infect Dis.
2007; 44:1647–1656. [PubMed: 17516411]
12. Hoffman RM, Black V, Technau K, van der Merwe KJ, Currier J, Coovadia A, et al. Effects of
highly active antiretroviral therapy duration and regimen on risk for mother-to-child transmission
of HIV in Johannesburg, South Africa. J Acquir Immune Defic Syndr. 2010; 54:35–41. [PubMed:
20216425]
CHIBWESHA et al. Page 5
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

13. Warszawski J, Tubiana R, Le Chenadec J, Blanche S, Teglas JP, Dollfus C, et al. Mother-to-child
HIV transmission despite antiretroviral therapy in the ANRS French Perinatal Cohort. AIDS.
2008; 22:289–299. [PubMed: 18097232]
14. Stringer EM, Chintu NT, Levy JW, Sinkala M, Chi BH, Muyanga J, et al. Declining HIV
prevalence among young pregnant women in Lusaka, Zambia. Bull World Health Organ. 2008;
86:697–702. [PubMed: 18797645]
15. Chi BH, Chintu N, Lee A, Stringer EM, Sinkala M, Stringer JS. Expanded services for the
prevention of mother-to-child HIV transmission: field acceptability of a pilot program in Lusaka,
Zambia. J Acquir Immune Defic Syndr. 2007; 45:125–127. [PubMed: 17460478]
16. Mwapasa V, Rogerson SJ, Kwiek JJ, Wilson PE, Milner D, Molyneux ME, et al. Maternal syphilis
infection is associated with increased risk of mother-to-child transmission of HIV in Malawi.
AIDS. 2006; 20:1869–1877. [PubMed: 16954728]
17. Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Semrau K, Mwiya M, et al. Effects of early,
abrupt weaning on HIV-free survival of children in Zambia. The New England journal of
medicine. 2008; 359:130–141. [PubMed: 18525036]
18. Kuhn L, Aldrovandi GM, Sinkala M, Kankasa C, Mwiya M, Thea DM. Potential impact of new
WHO criteria for antiretroviral treatment for prevention of mother-to- child HIV transmission.
AIDS. 2010; 24:1374–1377. [PubMed: 20568677]
19. Killam WP, Tambatamba BC, Chintu N, Rouse D, Stringer E, Bweupe M, et al. Antiretroviral
therapy in antenatal care to increase treatment initiation in HIV-infected pregnant women: a
stepped-wedge evaluation. AIDS. 2010; 24:85–91. [PubMed: 19809271]
20. Spensley A, Sripipatana T, Turner AN, Hoblitzelle C, Robinson J, Wilfert C. Preventing mother-
to-child transmission of HIV in resource-limited settings: the Elizabeth Glaser Pediatric AIDS
Foundation experience. Am J Public Health. 2009; 99:631–637. [PubMed: 18703458]
21. Bolu OO, Allread V, Creek T, Stringer E, Forna F, Bulterys M, et al. Approaches for scaling up
human immunodeficiency virus testing and counseling in prevention of mother-to-child human
immunodeficiency virus transmission settings in resource-limited countries. Am J Obstet Gynecol.
2007; 197:S83–89. [PubMed: 17825654]
22. Mtapuri-Zinyowera S, Chideme M, Mangwanya D, Mugurungi O, Gudukeya S, Hatzold K, et al.
Evaluation of the PIMA Point-of-Care CD4 Analyzer in VCT Clinics in Zimbabwe. J Acquir
Immune Defic Syndr. 2010; 55:1–7. [PubMed: 20622679]
23. Shumbusho F, van Griensven J, Lowrance D, Turate I, Weaver MA, Price J, et al. Task shifting for
scale-up of HIV care: evaluation of nurse-centered antiretroviral treatment at rural health centers
in Rwanda. PLoS Med. 2009; 6:e1000163. [PubMed: 19823569]
24. Sanne I, Orrell C, Fox MP, Conradie F, Ive P, Zeinecker J, et al. Nurse versus doctor management
of HIV-infected patients receiving antiretroviral therapy (CIPRA-SA): a randomised non-
inferiority trial. Lancet. 2010; 376:33–40. [PubMed: 20557927]
25. Stringer JS, Zulu I, Levy J, Stringer EM, Mwango A, Chi BH, et al. Rapid scale-up of
antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA.
2006; 296:782–793. [PubMed: 16905784]
CHIBWESHA et al. Page 6
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

Figure 1.
Locally weighted regression line depicting the association between duration of antenatal
HAART and HIV transmission. (Note: This analysis is restricted to women who initiated
HAART during pregnancy.)
CHIBWESHA et al. Page 7
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
CHIBWESHA et al. Page 8
Table 1
Factors associated with mother-to-child HIV transmission
N Value
Mothers with infant
HIV PCR results
available (N = 1,813)
Mothers with HIV-
negative infants (N =
1,754)
Mothers with HIV-
positive infants (N =
59) Crude OR (95% CI) Adjusted OR (95% CI)
Age 1,813 29 years (SD +/−
5)
≤ 24 years 327 315 (18.0%) 12 (20.3%) 1.0 1.0
25 – 29 years 622 601 (34.3%) 21 (35.6%) 0.9 (0.5 – 1.9) 0.9 (0.4 – 2.0)
30 – 34 years 560 540 (30.8%) 20 (33.9%) 1.0 (0.5 – 2.0) 1.1 (0.5 – 2.4)
≥ 35 years 304 298 (17.0%) 6 (10.2%) 0.5 (0.2 – 1.4) 0.6 (0.2 – 1.6)
Education 1,813
Secondary or tertiary 878 858 (48.9%) 20 (33.9%) 1.0
None or primary 715 687 (39.2%) 28 (47.5%) 1.8 (1.0 – 3.1) 1.8 (1.0 – 3.2)
Unknown 220 209 (11.9%) 11 (18.6%) 2.3 (1.1 – 4.8) 2.3 (1.1 – 5.1)
Marital status 1,753
Married/cohabiting 1,637 1,585 (93.4%) 52 (92.9%) 1.0
Other 116 112 (6.6%) 4 (7.1%) 1.1 (0.4 – 3.1)
GA at 1st ANC visit 1,813 21 weeks (SD +/−
6)
≤ 20 weeks 605 584 (33.3%) 21 (35.6%) 1.0
21 – 27 weeks 980 948 (54.0%) 32 (54.2%) 0.9 (0.5 – 1.6)
≥ 28 weeks 228 222 (12.7%) 6 (10.2%) 0.8 (0.3 – 1.9)
BMI 977
< 25 kg/m2562 539 (57.6%) 23 (56.1%) 1.0
25 – 29 kg/m2360 343 (36.6%) 17 (41.5%) 0.9 (0.4 – 1.9)
≥ 30 kg/m255 54 (5.8%) 1 (2.4%) 0.4 (0.1 – 3.0)
Hemoglobin 1,813 11.0 g/dL (SD +/−
1.6)
≥ 10.0 g/dL 977 957 (54.6%) 20 (33.9%) 1.0 1.0
8.0 – 9.9 g/dL 267 254 (14.5%) 13 (22.0%) 2.5 (1.2 – 5.0) 1.7 (0.8 – 3.6)
≤ 7.9 g/dL 29 28 (1.6%) 1 (1.7%) 1.7 (0.2 – 13.2) 0.8 (0.1 – 6.9)
Not done 540 515 (29.4%) 25 (42.4%) 2.3 (1.3 – 4.2) 2.3 (1.2 – 4.5)
Syphilis screen 1,813
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
CHIBWESHA et al. Page 9
N Value
Mothers with infant
HIV PCR results
available (N = 1,813)
Mothers with HIV-
negative infants (N =
1,754)
Mothers with HIV-
positive infants (N =
59) Crude OR (95% CI) Adjusted OR (95% CI)
RPR non-reactive 1,316 1,275 (72.7%) 41 (69.5%) 1.0 1.0
RPR reactive 40 35 (2.0%) 5 (8.5%) 4.4 (1.7 – 11.9) 3.8 (1.3 – 10.7)
Not done 457 444 (25.3%) 13 (22.0%) 0.9 (0.5 – 1.7) 0.9 (0.5 – 1.7)
CD4+ count at entry 1,813 231 cells/uL (IQR
164 – 329)
≥ 350 cells/uL 250 246 (14.0%) 4 (6.8%) 1.0 1.0
200–349 cells/uL 511 501 (28.6%) 10 (16.9%) 1.2 (0.4 – 4.0) 0.8 (0.2 – 2.6)
< 200 cells/uL 446 422 (24.1%) 24 (40.7%) 3.5 (1.2 – 10.2) 2.0 (0.6 – 6.3)
Not done 606 585 (33.4%) 21 (35.6%) 2.2 (0.8 – 6.5) 1.9 (0.6 – 5.8)
GA at delivery 1,813 38 weeks (SD +/−
4)
37 – 41 weeks 1,069 1,033 (58.9%) 36 (61.0%) 1.0
< 32 weeks 65 63 (3.6%) 2 (3.4%) 0.9 (0.2 – 3.9)
32 – 36 weeks 445 428 (24.4%) 17 (28.8%) 1.1 (0.6 – 2.1)
≥ 42 weeks 234 230 (13.1%) 4 (6.8%) 0.5 (0.2 – 1.4)
Birth weight 1,792 2,900 g (SD +/−
400)
≥ 2,500 g 1,568 1,519 (87.7%) 49 (83.1%) 1.0 1.0
< 2,500 g 224 214 (12.3%) 10 (16.9%) 1.5 (0.7 – 2.9) 1.2 (0.6 – 2.5)
Duration of antenatal HAART 1,813 13 weeks (IQR 8
– 19)
≥ 13 weeks 1,188 1,161 (66.2%) 27 (45.8%) 1.0 1.0
9 – 12 weeks 196 189 (10.8%) 7 (11.9%) 1.6 (0.7 – 3.7) 1.8 (0.7 – 4.8)
5–8 weeks 242 234 (13.3%) 8 (13.6%) 1.5 (0.7 – 3.3) 2.0 (0.8 – 5.1)
≤ 4 weeks 187 170 (9.7%) 17 (28.8%) 4.3 (2.3 – 8.1) 5.5 (2.6 – 11.7)
GA: gestational age; ANC: antenatal care; BMI: body mass index; SD: standard deviation; IQR: interquartile range; OR: odds ratio; CI: confidence interval
J Acquir Immune Defic Syndr
. Author manuscript; available in PMC 2013 March 22.