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

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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.
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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
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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
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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.
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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).
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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.)
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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
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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.
... In addition, like other cellular DNA, mtDNA is susceptible to acquired mutations [53], and the accumulation of deleted mtDNA (MDD) is part of the ageing process [53,54]. It is noteworthy that mtDNA deletions have rarely been investigated in CHEU and an association with ARV drug exposure has never been demonstrated [55,56]. ...
... To date, Maagaard et al. reported such high prevalence of MDD (75%) in the blood of HIV-infected adults [68]. To our knowledge, two studies have investigated MDD in CHEU, one including Tanzanian children at birth reported a low frequency of MDD [56], and another including US children aged 18 months did not report MDD [55]. These three studies were not quantitative either and did not indicate the limit of positivity. ...
... Fourthly, some information were selfreported: "previous clinical consultations" or "hospital admissions", "smoking during pregnancy and breastfeeding", "alcohol consumption during pregnancy", "type of income" and "education of the mother". We also lack information on well-known factors associated with telomere shortening such as paternal age (55)(56)(57), consumption of drugs of addiction (58-60) and cytomegalovirus infection (61). Finally, we could not perform long-term follow of CHEU from South Africa because samples were not collect and store. ...
Thesis
L’universalisation des traitements antirétroviraux (ARV) couplée à l’augmentation de la couverture ARV chez les femmes enceintes et allaitantes infectées par le VIH voit l’émergence d’une population grandissante d’enfants non infectés nés de mères séropositives, exposés à la fois au VIH et aux ARV maternels de la conception à la petite enfance. Si l’impact de ces expositions questionne sur la santé de ces enfants et fait l’objet de maintes études, la prophylaxie ARV postnatale qui leur ait administrée dans le cadre de la prévention de la transmission mère-enfant (TME) du VIH nécessite elle aussi être rigoureusement évaluée, ces ARV restant donnés à des enfants non infectés. Dans ce contexte, ces travaux de thèse ont consisté à évaluer la toxicité génomique aigüe et sur le long terme du lopinavir/ritonavir (LPV/r) ou de la lamivudine (3TC) utilisés en prophylaxie infantile pendant un an pour prévenir la TME du VIH par l’allaitement lors de l’essai PROMISE PEP mené dans quatre pays d’Afrique Sub-saharienne (Afrique du Sud, Burkina Faso, Ouganda et Zambie) entre novembre 2009 et mai 2012. Si cette prophylaxie étendue à toute la période de l’allaitement a montré son efficacité, avec des taux de transmission à un an de 1.4% et 1.5% pour le LPV/r et le 3TC respectivement, les recommandations actuelles de l’Organisation Mondiale de la Santé préconisent cependant une prophylaxie à base de névirapine (NVP) ou d’azidothymidine combinée à la NVP plafonnée à 12 semaines. Nos travaux indiquent que les deux prophylaxies se trouvaient associées à une prévalence importante d’enfants exposés non infectés présentant une déplétion de l’ADN mitochondrial (diminution du nombre de copies supérieure ou égale à 50% de la valeur initiale) au cours de la première année de vie. Ils ont également mis en évidence la présence d’ADN mitochondrial délétés chez la quasi-totalité des enfants dès l’initiation de la prophylaxie, démontrant ainsi une forte instabilité génomique. Toutefois, aucune association avec la croissance et le développement neuro-psychomoteur de ces enfants à 6 ans n’a été mise en évidence, alors que la déplétion ne persistait plus à cet âge-là et que les délétions sont irréversibles. Le raccourcissement de la longueur des télomères observé à un an n’a quant à lui montré aucune association avec les deux ARV et n’a eu aucun impact sur la santé des enfants à 6 ans. Ces travaux de thèse contribuent à l’évaluation globale de l’innocuité de la prophylaxie ARV utilisée chez les enfants exposés non infectés mais sont également d’intérêt pour ceux qui sont infectés et dont le traitement de première intention intègre le LPV/r et/ou le 3TC.
... This high proportion meant that the PMTCT interventions could not be effective because the World Health Organization recommended that the ARV initiation in HIV-infected pregnancies should be started during the early date of the first trimester as the effectiveness of early diagnosis of HIV and early initiation of ARV in HIVpositive pregnancies was noted in several evidence. 17,18 Another notable point of the finding in this study was that there was a difference between the HIV testing rate and the HIV counselling rate among study pregnancies. To the best of the researcher's knowledge, this issue may be concerned with the provider sides of the PMTCT program and this might be because the PMTCT providers tested the HIV status of the pregnancies without any counselling. ...
Article
Full-text available
Background: Globally, about 1.3 million human-immunodeficiency virus (HIV)-positive women get pregnant once a year, and about 160,000 children are born with the HIV. This study was conducted to investigate pregnant women's awareness, attitude, and practice regarding the prevention of mother to child HIV transmission (PMTCT).Methods: This cross-sectional study collected qualitative data from 152 pregnant women registered in the health facilities in Taungoo township. Simple random sampling was applied to cull three out of total rural health centres and systematic random sampling was exercised to recruit the required pregnant women from all registered pregnancies. The semi-structured questionnaire and statistical package for the social sciences (SPSS) version 23 were used for data collection and analysis accordingly.Results: In overall, the pregnant women studied had good awareness (56.6%), favourable attitude (60.5%), and good practice (55.3%) on PMTCT services. 78.3% were aware of the PMTCT project and knew that a baby can be prevented from HIV transmission by an HIV mother, 57.8% agreed that counselling and testing for HIV during pregnancy are important and 85.5% were tested for HIV. The awareness was associated with the family type (p=0.049), the attitude was associated with age (p=0.048), residence (p=0.024), and frequency of antenatal visits during current pregnancy (p=0.021), and practice was associated with antenatal care delivery sites (p=0.038), husband's support for antenatal care (p=0.004) and taking antenatal services during a previous pregnancy (p=0.033).Conclusions: Many unsatisfactory findings regarding PMTCT services were noted. So, strategic interventions and effective approaches for getting the full coverage of PMTCT programs should be strengthened.
... The same is true for many other developed countries . African countries such as the Ivory Coast 3.28% (Lasme-Guillao et al., 2011), Cameroon 4.6% (Tsingaing et al., 2011), Mali 1.98% (Traore et al., 2011), Malawi 4.1% (Kim et al., 2013), South Africa 3.3% (Mnyani et al., 2014), Zambia 3.3% (Chibwesha et al., 2011) and Ethiopia 2.3% (Kassaw et al., 2020). Schumann at al. (2020) have presented very low rates of MTCT. ...
Article
Full-text available
Despite the worldwide success of the introduction of human immunodeficiency virus (HIV) testing and treatment with antiretroviral drugs, HIV remains a real public health problem. Vertical mother-to-child transmission is a form responsible for many cases of new infections. The objective of the study is to carry out an inventory of mother-to-child transmission of HIV-1 in the departments of Mono and Couffo. A total of 374 drops of dry blood (DBS) were collected from infants born to HIV-positive mothers during the year 2019. Information on the type of treatment, the type of infant diet was also collected. These different samples were used for RNA extraction. The early diagnosis of these infants as well as the determination of the viral load were carried out by reverse transcriptase-Polymerase Chain Reaction (RT-PCR) using the Roche automated system. The results showed that 93.41% of the newborns included in this study tested negative for early detection by RT-PCR. Significant associations were observed between early diagnosis of newborns and maternal feeding pattern, PMTCT protocol, and maternal viral load with regression logistics and Chi-square testing. Monoprophylaxis was predominant in the protocol for the prevention of neonatal mother-to-child transmission (PMTCT) (96.28%). The national program for the prevention of vertical transmission of HIV from mother to child deserves to be continued and strengthened with the objective of zero newborns infected at birth in the departments of Mono and Couffo.
... However, in breastfeeding populations, intrauterine transmission is the major route of MTCT (39). Recent observational studies concluded that ART should be initiated at least 16 weeks (112 days) prior to the date of birth to achieve the desirable undetectable HIV VL by the time of delivery (40)(41)(42). In light of our finding of VS in >95% of women only after 126 days, an even earlier start of ART might be advantageous. ...
Article
Full-text available
Background Achieving and maintaining viral suppression (VS) in people living with HIV/AIDS on antiretroviral therapy (ART) remains a crucial clinical goal, more so in pregnancy to prevent mother-to-child-transmission (MTCT). There is a need to understand VS kinetics and barriers to achieving it in order to meet the target of eliminating HIV-MTCT by 2030. Methods HIV-infected pregnant women ≥20 weeks of gestation with different durations of Tenofovir/Lamivudine/Efavirenz exposures seeking antenatal care services at four primary health centres in high-density residential areas in Harare, Zimbabwe were enrolled in the University of Zimbabwe Birth Cohort Study. Plasma viral load (VL) was quantified by reverse transcriptase–polymerase chain reaction. Demographic, clinical, socio-economic and HIV- and ART-related factors were tested in multivariable logistic regression analyses as potential predictors for VS and undetectable VL. Results From March 2016 to June 2019, 608 HIV-infected pregnant women were enrolled. 63 (10.4%) were self-reported-ART-naïve; 324 (53.3%) and 221 (36.3%) initiated ART pre- and post-conception, respectively. Time from ART initiation to VS (VL ≤ 1,000 copies/ml) in 95% of the women was 126 days. Overall lack of VS (VL > 1,000 copies/ml) was observed in 133 (21.9%) women being 76.2, 27.4 and 7.7% in self-reported-ART-naïve, post-conception and pre-conception groups, respectively. Undetectable VL (≤ 50 copies/ml) was observed in 371 (61.2%) and low-level viremia (51–1,000 copies/ml) in 102 (16.8%) women. In multivariable models for all participants regardless of ART exposure, being on ART was the strongest predictor for both VS and undetectable VL (odds ratio 95% confidence interval, OR (CI): 8.9(4.2–19.5) and 8.1(3.2–24.4), respectively). For women on ART, duration of ART use >126 days was the strongest predictor with OR (CI): 6.7(3.3–14.0) for VS and 8.5(5.6–13.1) for undetectable VL. Other relevant predictors for favourable virological outcomes were older maternal age, HIV-status disclosure, absence of ART side effects and self-reported depression. Having a spouse/intimate partner on ART predicted a 4 times higher likelihood for VS. Discussion Lack of VS was frequently observed in this Harare cohort of pregnant women, mainly due to new HIV diagnosis, hence not being on ART and suboptimal duration of ART exposure. Since VS for 95% of women needed about 4 months of ART exposure, eliminating HIV-MTCT will require timely screening and commencing women together with their spouses/intimate partners on ART before pregnancy or early after conception. Clinical Trial Registration www.ClinicalTrials.gov , identifier: NCT04087239.
... the same is true for many other developed countries [11]. African countries such as the Ivory Coast [12], Cameroon [13], Mali [14], Malawi [15], South Africa [16], Zambia [17] and Ethiopia [18], Schumann at al., [19] have also had to obtain very low rates of MTCT. some countries have even reported having completely eliminated mother-to-child transmission of the virus [20,21]. ...
Preprint
Full-text available
Background: Despite worldwide success of introducing HIV testing and treatment with antiretroviral drugs, HIV remains a real public health problem. Vertical mother-child transmission is a form responsible for many cases of new infections. This study was therefore carried out in order to reduce the prevalence of mother-to-child transmission of HIV-1 in the departments of Mono and Couffo. Method: For this purpose, a total of 374 dry blood spots (DBS) were collected from infants born to HIV-positive mothers during the year 2019, and these DBS were used for the molecular diagnosis of HIV1 in these infants. Information on the type of treatment, the type of diet of infants was also collected. The viral loads of the mothers before delivery were determined after the last antenatal visits. To do so, a venous blood sample was taken from an EDTA tube. These different samples were used for DNA extraction. The early diagnosis of these infants as well as the determination of the viral load were carried out by RT-PCR using the Roche automated system. The results were analyzed with the chi-square test on the SPSS software. Result: The results showed that 51% of the newborns included in the study were male and the vast majority of the newborns were in the 0-6 month age group. 93.41% of the newborns included in this study were tested negative for early detection by RT-PCR. Significant links were observed between the early diagnosis of newborns and the mother's mode of feeding, the PMTCT protocol, and the viral load of the mothers. Monoprophylaxis was predominant in the newborn PMTCT protocol (96.28%). Conclusion: The national program for the prevention of vertical transmission of HIV from mother to child deserves to be continued and strengthened with the objective of zero newborns infected at birth in the departments of Mono and Couffo.
... [16][17][18] Depending on the baseline VL, a maximum of 12-16 weeks is deemed sufficient to suppress plasma VL in pregnant women. [16][17][18][19][20] An 8% reduction in the odds of HIV transmission with each additional week of treatment among women initiating ART during pregnancy has been reported. 16 Zero in utero and intrapartum HIV transmission has been documented among infants born to women who conceived on ART, continued treatment during pregnancy, and delivered with a plasma VL ,50 copies/mL. ...
Article
Background: Elimination of mother-to-child transmission of HIV (eMTCT) requires sustained viral load suppression (VLS) during pregnancy and breast-feeding among women living with HIV (WLHIV). Antenatal antiretroviral therapy (ART) coverage is reported at >95% in South Africa, but VLS rates are unknown. We describe maternal VL burden around time of delivery at four tertiary obstetric units (TOUs) in Gauteng Province. Methods: Between June 2018-March 2019, routine point-of-care (PoC) maternal HIV VL and early infant diagnosis (EID) testing was implemented at three TOUs in Johannesburg and one in Tshwane district. WLHIV and HIV-exposed neonates were eligible for HIV VL (Xpert® HIV-1 VL) and EID (Xpert® HIV-1 EID or m-PIMA™ HIV1/2 detection) testing around time of delivery, respectively. Proportions of viraemic women and intrauterine (IU)-infected neonates were calculated among valid PoC results. Results: Among 8147 live-births to WLHIV, 2769 (34·0%) women and 4333 (53·2%) neonates had valid PoC results. Median VL at delivery was <40 copies/mL (interquartile range: 0-398). The proportion of women with a VL<50, 50-<1000 and ≥1000 copies/mL was 63·6%, 13·9% and 22·4%, respectively. There were 65/4333 (1·5%) IU-infected neonates. Among 1449 mother-neonate pairs with both VL and EID results, IU transmission by VL threshold was 3/946 (0·3%), 6/187 (3·2%) and 25/316 (7·9%) for VL<50, 50-<1000 and ≥1000 copies/mL, respectively (p<0·001). Conclusion: Despite high ART coverage, >1/3 of WLHIV had a VL≥50 copies/mL at delivery. Among mother-neonate pairs, maternal VL≥50 copies/mL accounted for 31/34 (91%) IU-infections. Improvement in the quality of HIV care among WLHIV is essential if South Africa is to achieve eMTCT.
Article
There are missed opportunities for the prevention of mother-to-child transmission of HIV (PMTCT) in Nigeria. However, little is known about the geographic variation. We examined the geographic pattern in the missed opportunities for HIV testing among antenatal care (ANC) attendees and initiation t on antiretroviral therapy (ART) in Nigeria. This study was an analysis of aggregated state-level data on 2,875,370 ANC attendees from the 2019 national HIV/AIDS health sector data. We performed descriptive statistics and explanatory spatial data analysis. Overall, the missed opportunity for HIV testing was 9.3%, ranging from 1.8% in the South South to 14.5% in the North West. The missed opportunity for HIV testing ranged from 0.2% in Imo State to 25.2% in Kaduna State. The local indicator of spatial association cluster map showed a concentration of cold spots in the South and hot spots in the North. The overall missed opportunity for ART was 9.5%, ranging from 7.4% in the South West to 11.1% in the NorthCentral. It was lowest in Adamawa State (0%), while Enugu State had the highest (32.2%). Missed opportunities for PMTCT among women attending ANC in Nigeria occur at varying degrees across the states, with higher levels in the northern region.
Article
Full-text available
Background Eliminating mother-to-child transmission of HIV (MTCT) in sub-Saharan Africa is hindered by limited understanding of HIV-testing and HIV-care engagement among pregnant and breastfeeding women. Methods We investigated HIV-testing and HIV-care engagement during pregnancy and breastfeeding from 2014 to 2018 in the Agincourt Health and Demographic Surveillance System (HDSS). We linked HIV patient clinic records to HDSS pregnancy data. We modelled time to a first recorded HIV-diagnosis following conception, and time to antiretroviral therapy (ART) initiation following diagnosis using Kaplan-Meier methods. We performed sequence and cluster analyses for all pregnancies linked to HIV-related clinic data to categorise MTCT risk period engagement patterns and identified factors associated with different engagement patterns using logistic regression. We determined factors associated with ART resumption for women who were lost to follow-up (LTFU) using Cox regression. Results Since 2014, 15% of 10,735 pregnancies were recorded as occurring to previously (51%) or newly (49%) HIV-diagnosed women. New diagnoses increased until 2016 and then declined. We identified four MTCT risk period engagement patterns (i) early ART/stable care (51.9%), (ii) early ART/unstable care (34.1%), (iii) late ART initiators (7.6%), and (iv) postnatal seroconversion/early, stable ART (6.4%). Year of delivery, mother’s age, marital status, and baseline CD4 were associated with these patterns. A new pregnancy increased the likelihood of treatment resumption following LTFU. Conclusion Almost half of all pregnant women did not have optimal ART coverage during the MTCT risk period. Programmes need to focus on improving retention, and leveraging new pregnancies to re-engage HIV-positive women on ART.
Article
Background We investigated if initiating preventive care against HIV vertical transmission by antenatal HIV screening is independent of the patients’ source of financial reimbursement for the care received in sub-Saharan Africa. Methods Using information from the WHO’s Global Health Expenditure Database and the Demographic Health Surveys Database for 27 sub-Saharan countries, we used Spearman’s correlation and adjusted survey logistic regression to determine the potential relationship between enrollment in health insurance and the likelihood that expectant mothers would be offered antenatal HIV screening. Results We found that expectant mothers covered by health insurance were more than twice as likely to be offered antenatal screening for HIV compared to the uninsured. The likelihood differed by the type of insurance plan the expectant mother carried. Discussion Health insurance is more of a financial tool that this study finds to be necessary to boost the uptake of preventive and therapeutic HIV care in SSA. Conclusion The ensuing disparity in receiving proper care could hinder achieving the goals of the 90-90-90 and the forthcoming 95-95-95 plan in SSA.
Article
We describe the history of mother-to-child-prevention, time to HIV diagnosis and antiretroviral therapy of 55 hospitalized HIV-positive children (median age, 5.7 months). Of 31 (56%) mothers who knew their HIV status prior to pregnancy, 11 (35%) did not attend antenatal clinics; those who did attend had poor viral suppression. Despite rapid recognition and access to treatment, 13% of hospitalized HIV-positive infants died. Strategies to reach the mothers driving vertical transmission are imperative.
Article
Full-text available
In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children. We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months. In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P=0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P=0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P=0.007). Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants.(ClinicalTrials.gov number, NCT00310726.)
Article
Full-text available
Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. Cross-sectional surveillance study of mother-infant pairs using umbilical cord blood samples collected between June 10, 2007, and October 30, 2008, from 43 randomly selected facilities (grouped as 25 service clusters) providing delivery services in Cameroon, Côte d'Ivoire, South Africa, and Zambia. All sites used at least single-dose nevirapine to prevent mother-to-child HIV transmission and some sites used additional prophylaxis drugs. Population nevirapine coverage, defined as the proportion of HIV-exposed infants in the sample with both maternal nevirapine ingestion (confirmed by cord blood chromatography) and infant nevirapine ingestion (confirmed by direct observation). A total of 27,893 cord blood specimens were tested, of which 3324 were HIV seropositive (12%). Complete data for cord blood nevirapine results were available on 3196 HIV-seropositive mother-infant pairs. Nevirapine coverage varied significantly by site (range: 0%-82%). Adjusted for country, the overall coverage estimate was 51% (95% confidence interval [CI], 49%-53%). In multivariable analysis, failed coverage of nevirapine-based services was significantly associated with maternal age younger than 20 years (adjusted odds ratio [AOR], 1.44; 95% CI, 1.18-1.76) and maternal age between 20 and 25 years (AOR, 1.28; 95% CI, 1.07-1.54) vs maternal age of older than 30 years; 1 or fewer antenatal care visits (AOR, 2.91; 95% CI, 2.40-3.54), 2 or 3 antenatal care visits (AOR, 1.93; 95% CI, 1.60-2.33), and 4 or 5 antenatal care visits (AOR, 1.56; 95% CI, 1.34-1.80) vs 6 or more antenatal care visits; vaginal delivery (AOR, 1.22; 95% CI, 1.03-1.44) vs cesarean delivery; and infant birth weight of less than 2500 g (AOR, 1.34; 95% CI, 1.11-1.62) vs birth weight of 3500 g or greater. In this random sampling of sites with services to prevent mother-to-child HIV transmission, only 51% of HIV-exposed infants received the minimal regimen of single-dose nevirapine.
Article
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We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. We randomly assigned 2369 HIV-1-positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth. Rates were compared with the use of the log-rank test. Among mother-infant pairs, 5.0% of infants were HIV-1-positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.)
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HIV transmission from mother-to-child remains a major cause of infant morbidity and mortality in resource-poor settings. There is consensus that women who need antiretroviral treatment should receive this during pregnancy and beyond, and that an appropriate antiretroviral prophylactic regimen should be given to those who do not yet need ongoing therapy. Infant feeding remains a major source of infection and new antiretroviral strategies, for mothers or children, are emerging with the potential to control this. Access to HIV testing and antiretroviral treatment or prophylaxis remain very limited in low resource settings and needs to be expanded.
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Without prevention, a third of HIV-exposed infants acquire HIV in breastfeeding populations before, during, or after delivery through mother-to-child transmission (MTCT). Whereas MTCT is now a sentinel event in resource-rich countries with antiretroviral prophylaxis, caesarean section, and avoidance of breastfeeding, this is not yet the case in resource-poor settings because breastfeeding is crucial to infant survival. Recent advances in postpartum maternal and infant prophylaxis enables safer breastfeeding, and increasing numbers of women accessing treatment and prevention of MTCT services in sub-Saharan Africa is leading to optimism that MTCT could be eliminated here also, as reflected in the UNAIDS target of 2015.
Article
Point-of-care (POC) CD4 testing was implemented at a stand-alone HIV voluntary testing and counseling centre in Harare, Zimbabwe. To validate the use of this new technology, paired blood samples were collected from 165 patients either by a nurse or a laboratory technician and tested using POC and conventional laboratory CD4 machines. Finger prick (capillary) blood was collected directly into the PIMA POC CD4 Analyzer cartridges and tested immediately, whereas venous blood collected into evacuated tubes was used for CD4 enumeration on a Becton Dickinson FACSCalibur. There was no significant difference in mean absolute CD4 counts between the POC PIMA and Becton Dickinson FACSCalibur platforms (+7.6 cells/microL; P = 0.72). Additionally, there was no significant difference in CD4 counts between the platforms when run by either a nurse (+18.0 cells/microL; P = 0.49), or a laboratory technicians (-3.1 cells/microL; P = 0.93). This study demonstrates that POC CD4 testing can be conducted in a voluntary testing and counseling setting for staging HIV-positive clients. Both nurses and laboratory technicians performed the test accurately, thereby increasing the human resources available for POC CD4 testing. By producing same-day results, POC CD4 facilitates immediate decision-making, patient management and referral and may help improve patient care and retention. POC CD4 may also alleviate testing burdens at traditional central CD4 laboratories, hence improving test access in both rural and urban environments.
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We reviewed the potential impact of new WHO criteria for antiretroviral therapy using data from 1025 HIV-infected women and infants followed for 24 months in Lusaka, Zambia. The new criteria require initiating therapy among 68% of pregnant women and, if fully effective, would prevent 92% of maternal deaths and 88% of perinatal and postnatal infections. Using CD4 cell count below 350 cells/microl, irrespective of clinical stage, is more efficient and stricter CD4 cutoffs would be counter productive.
Article
Background: Expanded access to combination antiretroviral therapy (ART) in resource-poor settings is dependent on task shifting from doctors to other health-care providers. We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients. Methods: This randomised non-inferiority trial was undertaken at two South African primary-care clinics. HIV-positive individuals with a CD4 cell count of less than 350 cells per microL or WHO stage 3 or 4 disease were randomly assigned to nurse-monitored or doctor-monitored ART care. Patients were randomly assigned by stratified permuted block randomisation, and neither the patients nor those analysing the data were masked to assignment. The primary objective was a composite endpoint of treatment-limiting events, incorporating mortality, viral failure, treatment-limiting toxic effects, and adherence to visit schedule. Analysis was by intention to treat. Non-inferiority of the nurse versus doctor group for cumulative treatment failure was prespecified as an upper 95% CI for the hazard ratio that was less than 1.40. This study is registered with ClinicalTrials.gov, number NCT00255840. Findings: 408 patients were assigned to doctor-monitored ART care and 404 to nurse-monitored ART care; all participants were analysed. 371 (46%) patients reached an endpoint of treatment failure: 192 (48%) in the nurse group and 179 (44%) in the doctor group. The hazard ratio for composite failure was 1.09 (95% CI 0.89-1.33), which was within the limits for non-inferiority. After a median follow-up of 120 weeks (IQR 60-144), deaths (ten vs 11), virological failures (44 vs 39), toxicity failures (68 vs 66), and programme losses (70 vs 63) were similar in nurse and doctor groups, respectively. Interpretation: Nurse-monitored ART is non-inferior to doctor-monitored therapy. Findings from this study lend support to task shifting to appropriately trained nurses for monitoring of ART. Funding: National Institutes of Health; United States Agency for International Development; National Institute of Allergy and Infectious Diseases.
Article
Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression. Between January 2004 to August 2008, 1142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA polymerase chain reaction at 4-6 weeks) were assessed with multivariate logistic regression. Mean age was 30.2 years (SD = 5.0) and median baseline CD4 count was 161 cells per cubic millimeter (SD = 84.3). HAART duration at time of delivery was a mean 10.7 weeks (SD = 7.4) for the 85% of women who initiated treatment during pregnancy and 93.4 weeks (SD = 37.7) for those who became pregnant on HAART. Overall MTCT rate was 4.9% (43 of 874), with no differences detected between HAART regimens. MTCT rates were lower in women who became pregnant on HAART than those initiating HAART during pregnancy (0.7% versus 5.7%; P = 0.01). In the latter group, each additional week of treatment reduced odds of transmission by 8% (95% confidence interval: 0.87 to 0.99, P = 0.02). Late initiation of HAART is associated with increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV-infected women.