Megazzini, Karen M Dr PH, PA-C*‡; Chintu, Namwinga MBChB‡; Vermund, Sten H MD, PhD‡§‖; Redden, David T PhD*; Krebs, Daniel W BS‡; Simwenda, Maureen MBChB¶; Tambatamba, Bushimbwa MBChB‡; Sinkala, Moses MBChB, MPH**; Stringer, Jeffrey S A MD†‡¶
From the *School of Public Health, Departments of Epidemiology and Biostatistics, University of Alabama, Birmingham, AL; †School of Medicine, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §Institute for Global Health; ‖Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN; ¶University of Zambia School of Medicine, Lusaka, Zambia; and **Catholic Medical Missions Boards, Lusaka, Zambia. Karen M. Megazzini is now at Westat, Rockville, MD.
Received for publication July 6, 2008; accepted March 12, 2009.
The programmatic work reported was supported by a multi-country grant to the Elizabeth Glaser Pediatric AIDS Foundation from the US Centers for Disease Control and Prevention (U62/CCU12354) through the President's Emergency Plan for AIDS Relief. Support for the intervention and evaluation components was provided by the University of Alabama at Birmingham and the Elizabeth Glaser Pediatric AIDS Foundation (EGSA 19-02).
Neither the Elizabeth Glaser Pediatric AIDS Foundation nor the Centers for Disease Control and Prevention was involved in data collection or management, nor were they engaged in direct contact with patients or identifiable patient data.
Data presented and published as an abstract at the XVII International AIDS Conference, August 3-8, 2008, Mexico City, Mexico.
All authors declare that they have no conflicts of interest.
Correspondence to: Dr. Karen M. Megazzini, Dr PH, PA-C, Westat, 1650 Research Boulevard, WB242, Rockville, MD 20850 (e-mail: firstname.lastname@example.org).
The number of perinatally acquired HIV infections can be reduced dramatically if pregnant women learn their HIV status and infected women and their exposed infants receive antiretroviral prophylaxis. HIV testing of pregnant women has traditionally been conducted in the antenatal care (ANC) setting to detect HIV early in pregnancy when the most efficacious treatment regimens can be implemented. Nonetheless, many women present to labor wards unaware of their HIV status either because they did not receive ANC or they did not receive HIV testing during ANC.1-5 Labor ward-based HIV testing and treatment provides an opportunity to reach many at-risk women and their infants.6-11
In 2003, we conducted an evaluation of the public sector prevention of mother-to-child transmission (PMTCT) of HIV program in Lusaka, Zambia. We found that only 30% of the HIV-infected/exposed women/infant pairs who received antenatal and delivery care within the Lusaka public sector clinics had ingested nevirapine (NVP) around the time of delivery.3 Our use of cord blood NVP improved the validity of this evaluation by assessing whether women who said that they had taken NVP had actually done so.12 Also, our use of a chart-based PMTCT stamp enabled us to identify each step of the prevention process to assess where women or infants were missed in counseling, diagnosis, informing of results, and treatment.13,14 A main contributing factor for prophylactic failure was that women had not learned their HIV status either because they were not offered or they had declined voluntary HIV counseling and testing during ANC.3
With this background, we conducted a cluster randomized trial of labor ward-based PMTCT services to improve program effectiveness (under review). The trail demonstrated feasibility of labor room counseling and testing and increased coverage of needed antiretroviral drugs for PMTCT.15 One of the interventions in the parent trial was provision of labor ward-based rapid HIV testing for women presenting in labor unaware of their HIV status. The primary outcome of the present analysis is to determine predictors of testing acceptance and successful administration of NVP among women assigned to the treatment arm of the parent trial who were eligible for voluntary counseling and testing (VCT) in the labor ward. The elapsed time between NVP ingestion and delivery was estimated to help determine how often the maternal NVP dose was administered at least 1 or 2 hours before delivery. We report both thresholds because prior pharmacologic analysis has suggested that NVP should be ingested at least 2 hours before delivery,16 whereas efficacy analysis has suggested that ingestion at least 1 hour before delivery may be sufficient.17
Between October 2005 and January 2006, we conducted the parent cluster randomized trial. Twelve public sector labor wards in Lusaka were stratified by clinic size and the 2003 estimate of population NVP coverage3 and then randomly allocated to the treatment and control arms of the study using Microsoft Excel 2003 (Microsoft Corp, Redmond, WA). The 6 public sector labor wards assigned to the treatment arm offered HIV counseling and point-of-care rapid HIV testing to women who presented to the labor ward unaware of their HIV status. NVP was provided to women who tested positive and to their infants.
The District Midwifery staff identified eligible women and provided them with VCT services. Women unaware of their HIV status were eligible for VCT if they were in the first stage of labor and the midwife deemed that there was sufficient time to complete counseling and testing before delivery. Midwives completed a 1-page data collection form on all women delivering in Lusaka District public sector clinics during the study period. The form contained nonidentifying patient information: age, gravidity, gestational age, place of first ANC visit, number of ANC visits, whether the woman had been offered and received VCT during ANC, her HIV status, and, if infected, whether she and her baby received NVP. A second 1-page form was completed on women who were eligible for rapid HIV testing in labor including whether the woman was offered VCT, whether she accepted VCT, her test result, the length of time it took to complete the rapid test and administer NVP, and elapsed time between NVP ingestion and delivery. To protect the women's anonymity, we did not collect exact times of admission, HIV testing, NVP administration, or delivery. Instead, the midwives indicated on the study form the nursing shift during which the woman was admitted (ie, morning, afternoon, or evening) and indicated the time range required for perform other activities, such as the elapsed time between drawing blood for the HIV test and administering NVP (or a look-alike calcium tablet for HIV-uninfected women, as described below), by selecting their choices from multiple choice lists provided on the data collection forms (eg, ≤45 minutes, 46-90 minutes, and >90 minutes).
Rapid HIV Testing
All women who chose to be tested provided written consent for HIV testing (which was standard procedure in Lusaka District at the time of the study). An HIV counseling “flip chart” was provided to help standardize the counseling message for each woman being counseled in labor. This flip chart was available in English and the 2 most common languages spoken in Lusaka: Nyanja and Bemba.
Women who chose to be tested were given the option of learning their HIV test result either before or after delivery. Those who chose to postpone learning their result until after delivery could nonetheless consent to NVP for themselves and their babies at the time of testing by indicating their choice on the consent form. The consent form explained that they would be offered a tablet despite the results of their HIV test. Women who tested positive were given a NVP tablet (200 mg) and their exposed infants received NVP syrup (2 mg/kg). We offered a calcium tablet that closely resembled NVP in size and color to all women who tested negative for HIV so as not to inadvertently disclose a woman's status during labor or stigmatize HIV-infected women by only providing tablets to those who tested positive.
We used a point-of-care rapid HIV testing strategy. Midwives were equipped with clip-on timers that allowed them to keep track of HIV tests that were running while they continued with their work. The standardized HIV testing algorithm used in Lusaka District ANC centers was employed. Women were screened for HIV using the Determine HIV-1/2 rapid test (Determine HIV-1/2; Abbott Laboratories, Abbott Park, IL), and positive results were confirmed with the Genie II HIV 1/2 rapid test (Genie II HIV-1/2; BioRad Laboratories, Hercules, CA). NVP was administered to all women who tested positive on the Determine test. Confirmatory HIV testing was done on those who tested positive using the Genie II rapid test either before or after delivery as time permitted.
Posttest HIV counseling was provided to all women before discharge from the center. Women were encouraged to receive posttest counseling and learn their results after delivery. Those who opted to learn their results before delivery could do so assuming that there was sufficient time for posttest counseling: a decision left to the discretion of the midwife. Women were informed of their infection status during the posttest counseling session unless they declined to learn their status at that time.
Generalized estimating equations (GEEs) were used to identify factors associated with HIV testing acceptance and NVP ingestion at least 1 and 2 hours before delivery. GEE models enabled us to account for the nonindependence of individuals within clinics that was necessary, given that labor wards (not individuals) had been randomized to the treatment and control arms in the parent trial. All our models accounted for delivery site. All variables significant at P < 0.10 level in the bivariate analyses were entered into the multivariable GEE models. All analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC). The study was approved by the Institutional Review Boards at the University of Alabama at Birmingham (Birmingham, AL) and the University of Zambia (Lusaka, Zambia).
During the 6-week intervention period of the parent trial, 2435 women gave birth to infants in the 6 labor wards offering rapid HIV testing and NVP prophylaxis, and 393 of the 2435 women (16%) were unaware of their HIV infection status. Among these women, 278 (71%) were in the first stage of labor and therefore eligible for VCT in the labor ward; 217 (78%) of them were offered VCT. The predominant reasons for which eligible women were not offered labor ward VCT are shown in Figure 1. Of the 217 women offered VCT, 146 of them (67%) agreed to pretest counseling and 82 of 146 (56%) agreed to and were tested for HIV while in labor. The predominant reason women were not tested for HIV after pretest counseling are also shown in Figure 1. The HIV prevalence among women tested in the labor ward was 28%.
HIV Testing Acceptance
Among the 217 women who were offered VCT in the labor ward, women who agreed to pretest counseling (n = 146) were similar to women who declined counseling (n = 71) in terms of age, cervical dilation, shift of admission, elapsed time between admission and delivery, and day of delivery (weekend versus weekday), but they differed in terms of gestational age, gravidity, number of ANC visits they attended, the place of their first ANC visit (Lusaka versus outside Lusaka or unbooked), and whether they had been offered VCT during ANC (Table 1). In multivariable analysis, the odds of HIV testing acceptance was greater among women who were primigravida compared with those who had been pregnant before [adjusted odds ratio (AOR) 1.5; 95% confidence interval (CI): 1.1 to 2.1] and among those who had not been offered VCT during ANC (AOR 3.7; 95% CI: 2.8 to 5.1) compared with those who declined VCT during ANC.
Timing of Tablet Administration
Of the 82 women tested for HIV in the labor ward, 71 of them (87%) received either a NVP tablet [21 (30%) for HIV seropositive women only] or a calcium tablet [50 (70%) for HIV seronegative women only] before delivery. Eleven women (13%) did not receive either tablet before delivery largely because they refused it (Fig. 2). Only once did a woman (HIV seronegative) deliver before the tablet could be administered. Tablets were administered to 85% (60 of 71) of women >1 hour before delivery and to 66% (47 of 71) of women > 2 hours before delivery (Fig. 2).
Women who received a tablet >1 hour before delivery were similar to those who received a tablet ≤1 hour before delivery with respect to age, gestational age, number of ANC visits, gravidity, shift of admission, time elapsed between blood collection and tablet administration, and day of delivery (weekend versus weekday) (data not shown). However, in multivariable analysis adjusted for the place of first ANC visit, women who received a tablet >1 hour before delivery were more likely to be in the latent phase of labor (cervical dilation 1-3 cm) at the time of admission (AOR 11.5; 95% CI: 4.5 to 29.2, Table 2). Tablet ingestion >2 hours before delivery was also associated with cervical dilation. In multivariable analysis, the odds of ingesting NVP >2 hours before delivery was greater for women who were dilated 1-3 cm at the time of admission compared with women dilated 4 or more centimeters (AOR 11.4; 95% CI: 4.7 to 27.5, Table 3) and among women who received 3 or more ANC visits compared with women who received 2 or fewer visits (AOR 3.7; 95% CI: 1.8 to 7.5, Table 3).
In bivariate analysis, the length of time that elapsed between admission and delivery was associated with HIV testing acceptance (Table 1) and ingestion of NVP >1 hour (Table 2) and >2 hours before delivery (Table 3). However, due to the presence of moderate colinearity between variables for cervical dilation and time between admission and delivery, we only used the cervical dilation variable as the more clinically relevant factor for the models.
We found that rapid HIV testing is feasible in busy Lusaka labor wards and that many Zambian women were receptive to labor ward-based VCT services. The District midwifery staff successfully identified 98% (387 of 393) of women who presented in labor unaware of their HIV status. Among those eligible for VCT in labor, two-thirds agreed to be counseled and just over half of the women who received counseling were tested for HIV. The rate of testing acceptance among women counseled in the labor ward (56%) was lower than the acceptance rates seen in public sector ANC centers in Lusaka,3 or that has been observed in other successful ANC-based PMTCT programs in sub-Saharan Africa.4,7,18 This is not surprising, given the labor ward environment and the fact that many of the women had refused testing during ANC. We found that this intervention was particularly beneficial to women who had not previously been offered VCT during their pregnancy.
Overall, 29% (82 of 278) of eligible women were tested for HIV in the labor ward using an opt-in, testing strategy, somewhat lower than labor ward testing uptake (40%) in Nairobi's Kenyatta National Hospital,2 and what has been reported in clinical trial settings.6,11 The fact that written consent was required in Lusaka for VCT at the time of our study may have inhibited some women.
Among those who were tested in the labor ward, 87% (71 of 82) ingested a tablet (either NVP or calcium) before delivery. We estimated the elapsed time between tablet administration and delivery and found that 85% women tested during labor ingested the tablet >1 hour before delivery and 67% ingested NVP >2 hours before delivery. The timing of tablet administration was similar among HIV-infected (NVP) and HIV-uninfected (similar appearing inert calcium tablet) women. Although subtherapeutic concentrations of NVP (<100 ng/mL) have been reported in infants born to women who received NVP <2 hours before birth,16 maternal NVP dosing <2 hours before delivery was not associated with vertical HIV transmission in a phase 3 trial of infant NVP versus NVP plus zidovudine at birth.19 Maternal dosing ≤1 hour before delivery was associated with vertical transmission in a study in Zambia.17 We found that NVP was successfully administered to the majority of women according to either dosing standard (ie, 1 or 2 hours before delivery). We also noted that the majority of women (83%) chose to learn their HIV status while in labor demonstrating that most women would prefer not to wait until after delivery to learn their test results, similar to findings in India.11
Two factors have likely contributed to this high rate of treatment “success,” that is, tablet administration >1 hour before delivery. First, this study utilized a point-of-care HIV testing strategy in which HIV testing was performed by midwives in the labor ward as opposed to sending the specimens to the laboratory for testing. In the Mother-Infant Rapid Intervention at Delivery study, point-of-care testing was shown to significantly shorten testing time and improve the proportion of test results that were received before delivery over laboratory-based testing.20 In our study, 75% (53 of 71) of the women tested for HIV received their tablet (NVP or calcium) within 45 minutes of the time their blood was collected for HIV testing. Tablet administration within 45 minutes of testing did not differ according to serostatus (data not shown). Second, most women who received HIV testing were in the early stages of labor. This provided a wide window of opportunity for midwives to complete testing and administer treatment before delivery was imminent.
Cervical dilation at the time of admission was an important and practical predictor of treatment success. We found that women dilated 1-3 cm were significantly more likely to receive treatment >1 hour (and >2 hours) before delivery than those dilated ≥4 cm. Unlike the Mother-Infant Rapid Intervention at Delivery study, we did not find that admission to the labor ward during the evening shift was associated with lower testing acceptance.
For labor ward-based VCT services to be optimally effective, eligible women must be identified, tested, and, if infected, must receive antiretroviral prophylaxis ideally at least 1 hour before delivery. In our study, we identified 2 predominant areas of missed opportunities. Among the women who were eligible for VCT in the labor ward, 22% (61 of 278) were not offered VCT and 49% (135 of 278) did not agree to either HIV counseling or testing in the labor ward. At the time of this study, HIV testing in Lusaka public sector clinics was performed using an opt-in testing strategy that involved pretest counseling and required women to sign an informed consent form before testing, which may have contributed to this attrition.
In this study, we employed the same opt-in testing strategy with some modifications to facilitate its use in a labor ward setting, for example, we provided flip charts to aid pretest counseling and trained midwives to perform rapid HIV tests in the labor ward. Others have shown that HIV testing acceptance can be improved by using an opt-out testing strategy21,22 that involves systematic HIV testing of all patients unless they decline testing. We suspect that had opt-out testing strategy been in place in Lusaka public labor wards at this time of this study, considerably more women may have benefited from the counseling and testing services offered. In addition to improving testing acceptance, opt-out testing would have theoretically shortened, or eliminated, the time needed for pretest counseling resulting in women being tested and treated earlier in labor.
Our study has potential limitations. Midwives were tasked with the responsibility of identifying women eligible for VCT in the labor ward and whether women were offered VCT was left of the discretion of the midwives. There was a tendency for midwives to offer VCT services to those in the earlier stages of labor and not offer services to those in more advanced labor. This may have inflated our reported acceptance rate and treatment success rate by excluding late-stage women from our study. We did not examine testing acceptance rates of women in the postpartum ward, another important venue for PMTCT. Factors associated with testing acceptance among postpartum women may differ from those of women in labor.
We estimated treatment success based on the timing of tablet administration: NVP to infected women and calcium to uninfected women. Given that only 21 women tested positive for HIV in the labor ward, we based our estimates of treatment success on the cohort of 71 women who received a tablet (NVP or calcium) in the labor ward. This is reasonable as we did not find a statistical difference in the time between tablet ingestion and delivery associated with serostatus. Similarly, the time required to complete the rapid test and administer the tablet was similar among seropositive and seronegative women, suggesting that there was no less perceived urgency among midwives to administer calcium to uninfected women than NVP to HIV-infected women.
For labor ward-based HIV counseling and testing to cover as many mother-infant pairs as possible, there will need to be prompt offering of services, particularly to women in later stages of labor. Rapid HIV testing is feasible in busy Lusaka labor wards and NVP can be successfully administered to women who test seropositive using an opt-in testing strategy; 85% of women receiving VCT in labor took their pill >1 hour before delivery. Alternative HIV testing strategies, such as an opt-out approach as is recommended by the Centers for Disease Control and Prevention, UNAIDS, and World Health Organization,22-24 will surely further enhance testing acceptance and treatment success in labor ward settings.
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