Comparison of Two Strategies for Administering Nevirapine in HIV
Comparison of Two Strategies for Administering Nevirapine in HIV
Universal nevirapine (NVP) therapy (provision of the drug without HIV testing) has been suggested as potentially superior to targeted NVP therapy (provision of the drug to seropositive patients identified through voluntary HIV counseling and testing [VCT]) for perinatal HIV prevention in low-resource, high-prevalence settings. The authors postulated that uptake (the proportion of women who accept the strategy when offered) may be higher for universal therapy, since it does not require a woman to learn her serostatus; they further postulated that adherence (the proportion of women who actually ingest the NVP tablet at labor onset) may be higher for targeted therapy, since knowledge of serostatus could motivate better adherence. Two clinics in Lusaka, Zambia were assigned to provide either the targeted or universal strategy. Halfway through the study period, the approach offered at each clinic was crossed over. Adherence was assessed by liquid chromatographic assay for NVP of cord blood. Regarding uptake, 1524 pregnant women were offered participation, and 1025 (67%) accepted. Of 694 women offered enrollment in the universal strategy, 496 (71%) accepted; of 830 women offered enrollment in the targeted strategy, 529 (64%) accepted (p < .01). Uptake was similar at both clinics for the universal strategy: 250 of 339 (74%) at clinic A and 246 of 355 (69%) at clinic B (p = .2), but differed significantly between clinics for the targeted strategy: 229 of 316 (72%) at clinic A and 300 of 514 (58%) at clinic B (RR, 1.51; 95% CI, 1.23, 1.86). Increased uptake correlated with having been offered the universal rather than the targeted strategy (AOR, 1.5; 95% CI, 1.1, 2.1), attendance at clinic A (AOR, 1.4; 95% CI, 1.01, 2.0), and maternal report of a prior fetal or infant death (AOR, 1.6; 95% CI, 1.1, 2.5). Regarding adherence, in the universal strategy, 40 of 103 women (39%) were nonadherent compared with 25 of 98 women (26%) in the targeted strategy (RR, 1.5; 95% CI, 1.004, 2.3). Failure to adhere correlated with participation in the universal strategy (AOR, 2.0; 95% CI, 1.04, 4.2) and illiteracy (AOR, 2.6; 95% CI, 1.2, 5.3). In high-prevalence settings with adequate VCT services, uptake of NVP using the universal or targeted approach appears comparable. However, the universal strategy may result in better uptake in clinics with less well-functioning VCT services (as with clinic B). Adherence to the single-dose NVP intervention was lower among women who did not learn their HIV status. Programs that seek to save the greatest possible number of infants from perinatal HIV acquisition should consider a combination approach, in which women who desire HIV testing can access NVP through a targeted strategy, and women who do not desire testing can access NVP through a universal strategy.
Ninety percent of global mother-to-child HIV transmission occurs in sub-Saharan Africa, with an estimated 800,000 new perinatal infections in 2001. Since essentially all infected infants will die prematurely, the impact of pediatric AIDS has already reversed hard-won gains in childhood mortality in much of the developing world. Nevirapine (NVP) provided as a single dose to the mother at the onset of labor and to the infant within 72 hours of birth reduces HIV transmission by 47% at 12 to 14 weeks of life compared with a very short course of zidovudine. Its benefit, although mitigated to some degree, persists even with breast-feeding.
Economic analyses have confirmed that intrapartum NVP would be a cost-effective use of scarce health care resources even in the poorest of countries. Marseille et al. proposed that a strategy of universal NVP administration (offering the drug to all pregnant women in a population, without testing them for HIV) would be economically favorable to a strategy of targeted NVP administration (offering NVP to only those women identified as seropositive) in certain high-prevalence, low-resource settings. These cost-effectiveness results are driven primarily by the low cost of NVP (<$4 per patient regimen when purchased over the counter or free if obtained from the manufacturer's donation program) and the comparatively high cost of voluntary HIV counseling and testing (VCT), estimated at $7 to $8 per person in high-prevalence settings where more posttest counseling of seropositive patients is done. Despite its hypothesized ease of administration and superior cost-effectiveness, the idea of offering NVP to pregnant women of unknown HIV serostatus is controversial.
In a prior publication, we used decision-analysis modeling to understand the clinical effectiveness and cost-effectiveness of strategies for NVP implementation. That investigation found the optimal choice between the universal and targeted approach hinged critically on two important areas of data uncertainty and could not be confidently made without additional information. First, it is possible that women who are offered access to NVP under a universal strategy may be more likely to uptake (i.e., participate in) the intervention, since it does not require them to learn their HIV status, than if a targeted approach were used. Thus, a universal strategy theoretically could reach a larger segment of the at-risk population. Second, it is possible that HIV-infected women participating in a universal strategy may be less likely to adhere to therapy (i.e., actually ingest the NVP tablet) than would women participating in a targeted strategy, since the latter know their status and may be more likely to perceive tangible infant benefit from taking the NVP. Our analysis found that a relatively small differential between strategies in uptake or adherence could cause the clinical effectiveness and cost-effectiveness balance to be tipped in favor of one or the other strategy. In response to these uncertainties, we launched a clinical trial to assess the uptake of the two strategies in a field setting and to measure the effect of HIV serostatus knowledge on likelihood of adherence to single-dose NVP.
Universal nevirapine (NVP) therapy (provision of the drug without HIV testing) has been suggested as potentially superior to targeted NVP therapy (provision of the drug to seropositive patients identified through voluntary HIV counseling and testing [VCT]) for perinatal HIV prevention in low-resource, high-prevalence settings. The authors postulated that uptake (the proportion of women who accept the strategy when offered) may be higher for universal therapy, since it does not require a woman to learn her serostatus; they further postulated that adherence (the proportion of women who actually ingest the NVP tablet at labor onset) may be higher for targeted therapy, since knowledge of serostatus could motivate better adherence. Two clinics in Lusaka, Zambia were assigned to provide either the targeted or universal strategy. Halfway through the study period, the approach offered at each clinic was crossed over. Adherence was assessed by liquid chromatographic assay for NVP of cord blood. Regarding uptake, 1524 pregnant women were offered participation, and 1025 (67%) accepted. Of 694 women offered enrollment in the universal strategy, 496 (71%) accepted; of 830 women offered enrollment in the targeted strategy, 529 (64%) accepted (p < .01). Uptake was similar at both clinics for the universal strategy: 250 of 339 (74%) at clinic A and 246 of 355 (69%) at clinic B (p = .2), but differed significantly between clinics for the targeted strategy: 229 of 316 (72%) at clinic A and 300 of 514 (58%) at clinic B (RR, 1.51; 95% CI, 1.23, 1.86). Increased uptake correlated with having been offered the universal rather than the targeted strategy (AOR, 1.5; 95% CI, 1.1, 2.1), attendance at clinic A (AOR, 1.4; 95% CI, 1.01, 2.0), and maternal report of a prior fetal or infant death (AOR, 1.6; 95% CI, 1.1, 2.5). Regarding adherence, in the universal strategy, 40 of 103 women (39%) were nonadherent compared with 25 of 98 women (26%) in the targeted strategy (RR, 1.5; 95% CI, 1.004, 2.3). Failure to adhere correlated with participation in the universal strategy (AOR, 2.0; 95% CI, 1.04, 4.2) and illiteracy (AOR, 2.6; 95% CI, 1.2, 5.3). In high-prevalence settings with adequate VCT services, uptake of NVP using the universal or targeted approach appears comparable. However, the universal strategy may result in better uptake in clinics with less well-functioning VCT services (as with clinic B). Adherence to the single-dose NVP intervention was lower among women who did not learn their HIV status. Programs that seek to save the greatest possible number of infants from perinatal HIV acquisition should consider a combination approach, in which women who desire HIV testing can access NVP through a targeted strategy, and women who do not desire testing can access NVP through a universal strategy.
Ninety percent of global mother-to-child HIV transmission occurs in sub-Saharan Africa, with an estimated 800,000 new perinatal infections in 2001. Since essentially all infected infants will die prematurely, the impact of pediatric AIDS has already reversed hard-won gains in childhood mortality in much of the developing world. Nevirapine (NVP) provided as a single dose to the mother at the onset of labor and to the infant within 72 hours of birth reduces HIV transmission by 47% at 12 to 14 weeks of life compared with a very short course of zidovudine. Its benefit, although mitigated to some degree, persists even with breast-feeding.
Economic analyses have confirmed that intrapartum NVP would be a cost-effective use of scarce health care resources even in the poorest of countries. Marseille et al. proposed that a strategy of universal NVP administration (offering the drug to all pregnant women in a population, without testing them for HIV) would be economically favorable to a strategy of targeted NVP administration (offering NVP to only those women identified as seropositive) in certain high-prevalence, low-resource settings. These cost-effectiveness results are driven primarily by the low cost of NVP (<$4 per patient regimen when purchased over the counter or free if obtained from the manufacturer's donation program) and the comparatively high cost of voluntary HIV counseling and testing (VCT), estimated at $7 to $8 per person in high-prevalence settings where more posttest counseling of seropositive patients is done. Despite its hypothesized ease of administration and superior cost-effectiveness, the idea of offering NVP to pregnant women of unknown HIV serostatus is controversial.
In a prior publication, we used decision-analysis modeling to understand the clinical effectiveness and cost-effectiveness of strategies for NVP implementation. That investigation found the optimal choice between the universal and targeted approach hinged critically on two important areas of data uncertainty and could not be confidently made without additional information. First, it is possible that women who are offered access to NVP under a universal strategy may be more likely to uptake (i.e., participate in) the intervention, since it does not require them to learn their HIV status, than if a targeted approach were used. Thus, a universal strategy theoretically could reach a larger segment of the at-risk population. Second, it is possible that HIV-infected women participating in a universal strategy may be less likely to adhere to therapy (i.e., actually ingest the NVP tablet) than would women participating in a targeted strategy, since the latter know their status and may be more likely to perceive tangible infant benefit from taking the NVP. Our analysis found that a relatively small differential between strategies in uptake or adherence could cause the clinical effectiveness and cost-effectiveness balance to be tipped in favor of one or the other strategy. In response to these uncertainties, we launched a clinical trial to assess the uptake of the two strategies in a field setting and to measure the effect of HIV serostatus knowledge on likelihood of adherence to single-dose NVP.
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