CONTEXT: A 2-dose intrapartum/newborn nevirapine regimen reduced perinatal human immunodeficiency virus (HIV) transmission in Ugandan women not receiving antenatal antiretroviral therapy (ART). However, it is unknown whether the addition of the 2-dose nevirapine regimen to standard ART would further reduce perinatal HIV transmission. OBJECTIVE: To determine whether a 2-dose nevirapine regimen can decrease perinatal transmission of HIV in nonbreastfeeding women receiving standard ART. DESIGN AND SETTING: International, blinded, placebo-controlled, phase 3 trial enrolling women between May 1997 and June 2000 at clinical sites providing care for HIV infection throughout the United States, Europe, Brazil, and the Bahamas. PARTICIPANTS: A total of 1270 women received nevirapine (n = 642) or placebo (n = 628). Infants were followed up for 6 months to determine HIV-infection status, which was available for 1248 deliveries. INTERVENTION: A 200-mg dose of oral nevirapine to women after onset of labor and a 2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours after birth. MAIN OUTCOME MEASURES: Detection of HIV infection in infants and grade 3 and 4 toxic effects in women and newborns. RESULTS: After review by the data and safety monitoring board, the trial was stopped early because the overall transmission rates were significantly lower than assumed for the study design. Antenatal ART included zidovudine alone in 23%; combinations without protease inhibitors in 36%; and combinations with protease inhibitors in 41%. Thirty-four percent of women had elective cesarean delivery. No significant safety concerns were identified for women or infants. Detection of HIV infection occurred in 9 (1.4%; 95% confidence interval [CI], 0.6%-2.7%) of 631 nevirapine group deliveries and 10 (1.6%; 95% CI, 0.8%-2.9%) of 617 placebo group deliveries. The 95% CI for the difference in transmission rate (-0.2) between the 2 study arms ranged from -1.5% in favor of nevirapine to 1.2% in favor of placebo (P =.82, Fisher exact test). The transmission rate was higher in women with lower baseline CD4 cell counts and higher delivery HIV RNA levels, but there was no significant difference between treatment arms in any subgroup. CONCLUSION: Risk of perinatal HIV transmission was low and no benefit from additional intrapartum/newborn nevirapine was demonstrated when women received prenatal care and antenatal ART, and elective cesarean section was made available.
CONTEXT: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. DESIGN: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.
OBJECTIVE: To assess the effect of a change in human immunodeficiency virus (HIV) testing policy on HIV testing rates in an urban maternity clinic population. METHODS: Since 1995, our institution has provided pretest counseling and voluntary HIV testing to all pregnant women. After the 1999 Institute of Medicine recommendation of HIV testing with patient notification as a routine component of prenatal care, we conducted a prospective study to determine whether this policy would increase our HIV screening rates. The intervention incorporated HIV testing into the routine battery of tests drawn at antenatal care. Not to be tested required active refusal. The intervention group was comprised of all women receiving an initial antenatal visit in one of our eight maternity clinics between August 1, 1999, and July 30, 2000. The control group was comprised of all women presenting for prenatal care in the same clinics during the year before the intervention. RESULTS: The 3415 women in the intervention group and 3778 controls were similar with respect to most demographic and risk factors. After the intervention, HIV testing increased from 75% to 88% (P <.001). Among all women in both years of the study, women who were in the intervention group, less than 20 years of age, or who had a history of substance abuse, were more likely not to refuse testing. CONCLUSION: After implementation of a policy of routine HIV testing with active patient refusal, HIV testing rates increased among pregnant women in our large, urban obstetric clinic population.
BACKGROUND: Recently the Department of Health announced the introduction in England of voluntary universal HIV screening in early pregnancy to prevent vertical transmission. New data have shown the importance of HIV infection in infants born to mothers who were HIV-negative in early pregnancy and who acquired HIV later in pregnancy or during lactation. This requires consideration of repeat testing in late pregnancy and testing of partners of pregnant women (expanded antenatal HIV testing). OBJECTIVE: To estimate cost effectiveness of expanded antenatal HIV testing in London (England) within the framework of universal voluntary HIV screening in early pregnancy. DESIGN: Incremental cost-effectiveness analysis. METHODS: Cost estimates of service provision for HIV-positive children and adults by stage of HIV infection were combined with estimates of health benefits for infants and parents and with costs of counselling and testing (testing costs). In a pharmacoeconomic model cost effectiveness was estimated for expanded antenatal HIV testing in London for universal and selective strategies. RESULTS: Testing costs in the plausible range of pounds sterling 4 to pounds sterling 40 translate into favourable incremental cost-effectiveness estimates for expanded antenatal HIV testing in London which is already at low numbers of vertical transmissions averted per 100000 pregnant women who test HIV-negative in early pregnancy. Favourable cost effectiveness for universal expanded testing would require testing costs in the lower range, whereas selective expanded testing may produce favourable cost effectiveness at testing costs close to pounds sterling 40. CONCLUSION: Based on pharmaco-economic considerations, the authors believe that implementation of expanded HIV testing in London should be considered.
BACKGROUND: The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life. METHODS: From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis. FINDINGS: Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups. INTERPRETATION: Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.
<b>BACKGROUND: </b>Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour.<b>METHODS: </b>In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR.<b>FINDINGS: </b>Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery.<b>INTERPRETATION: </b>A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.
OBJECTIVE: To develop an epidemiological basis for economic analyses of selective and universal antenatal screening strategies, and to apply it to the UK.
METHODS: The prevalence of higher-risk women and the prevalence of undiagnosed infection within groups of high-risk and low-risk women was estimated from surveillance and survey data. The numbers of women tested and the numbers of infected women who would be identified by universal and selective strategies were then calculated under a range of assumptions about the identification of higher-risk women and acceptance of testing.
RESULTS: In higher-risk women estimated prevalence of undiagnosed infection was between 0.06% and 2.8%, comparing well with independent estimates. In low-risk women, estimates ranged from 0.014% in London to 0.002% in the rest of the UK. If uptake among the high-risk women was the same in selective and universal strategies, universal testing would entail testing between 7100 (London) and 50000 (rest of England) additional women to detect an additional case. However, if selective screening identified only 60% of those at high risk and achieved only 60% acceptance compared with a universal programme, then universal screening would require only 1150 additional women to identify one additional case in London, compared to 6470 in Scotland and 13140 in the rest of the UK.
CONCLUSIONS: Overall prevalence does not form an adequate basis for determining screening strategy. Instead, universal screening can be justified either because the prevalence of HIV in the low-risk group is sufficiently high, or because it achieves sufficiently higher uptake relative to selective screening among those at higher risk.
OBJECTIVE: To estimate the cost effectiveness of universal, voluntary HIV screening of pregnant women in England. DESIGN: Cost effectiveness analysis. Cost estimates of caring for HIV positive children were based on the stage of HIV infection and calculated using data obtained from a London hospital between 1986 and 1996. These were combined with estimates of the health benefits and costs of antenatal screening so that the cost effectiveness of universal, voluntary antenatal screening for HIV infection in England could be estimated. MAIN OUTCOME MEASURES: Lifetime, direct costs of medical care of childhood HIV infection; life years gained as a result of the screening programme; net cost per life year gained for different pretest counselling costs; and different prevalence rates of pregnant women who were unaware that they were HIV positive. RESULTS: Estimated direct lifetime medical and social care costs of childhood HIV infection were pound178 300 using a 5% discount rate for time preference (1995-6 prices). In high prevalence areas screening pregnant women for HIV is estimated to be a cost effective intervention with a net cost of less than pound4000 for each life year gained. For areas with comparatively low prevalence rates, cost effectiveness could be less than pound20 000 per life year gained, depending on the number of pregnant women who are unaware that they are infected and local screening costs. CONCLUSIONS: Our results confirm recent recommendations that universal, voluntary antenatal HIV screening should be implemented in the London area. Serious consideration of the policy should be given for other areas in England depending on local prevalence and screening costs.
BACKGROUND: In Africa, the risk of mother-to-child transmission of HIV-1 infection is high. Short-course perinatal oral zidovudine might decrease the rate of transmission. We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan, Côte d'Ivoire. METHODS: From April, 1996, to February, 1998, all consenting, eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks' gestation and randomly assigned placebo or zidovudine (300 mg tablets), one tablet twice daily until the onset of labour, one tablet at onset of labour, and one tablet every 3 h until delivery. We used HIV-1-DNA PCR to test the infection status of babies at birth, 4 weeks, and 3 months. We stopped the study on Feb 18, 1998, when efficacy results were available from a study in Bangkok, Thailand, in which the same regimen was used in a non-breastfeeding population. FINDINGS: 280 women were enrolled (140 in each group). The median duration of the prenatal drug regimen was 27 days (range 1-80) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events. All babies were breastfed. Among babies with known infection status at age 3 months, 30 (26.1%) of 115 babies in the placebo group and 19 (16.5%) of 115 in the zidovudine group were identified as HIV-1 infected. The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7% and 12.2% (p=0.05) at 4 weeks, and 24.9% and 15.7% (p=0.07) at 3 months. Efficacy was 44% (95% CI -1 to 69) at age 4 weeks and 37% (-5 to 63) at 3 months. INTERPRETATION: Short-course oral zidovudine was safe, well tolerated, and decreased mother-to-child transmission of HIV-1 at age 3 months. Substantial efforts will be needed to ensure successful widespread implementation of such a regimen.
BACKGROUND: The benefit of antiretroviral therapy in reducing maternal-fetal transmission of HIV during pregnancy has caused a public policy debate about the relative benefits of mandatory HIV screening and voluntary HIV screening in pregnant women.
OBJECTIVE: To evaluate the benefits and risks of mandatory compared with voluntary HIV testing of pregnant women to help guide research and policy.
DESIGN: A decision analysis that incorporated the following variables: acceptance and benefit of prenatal care, acceptance and benefit of zidovudine therapy in HIV-infected women, prevalence of HIV infection, and mandatory compared with voluntary HIV testing.
MEASUREMENTS: The threshold deterrence rate (defined as the percentage of women who, if deterred from seeking prenatal care because of a mandatory HIV testing policy, would offset the benefit of zidovudine in reducing vertical HIV transmission) and the difference between a policy of mandatory testing and a policy of voluntary testing in the absolute number of HIV-infected infants or dead infants.
RESULTS: Voluntary HIV testing was preferred over a broad range of values in the model. At baseline, the threshold deterrence rate was 0.4%. At a deterrence rate of 0.5%, the number of infants (n = 167) spared HIV infection annually in the United States under a mandatory HIV testing policy would be lower than the number of perinatal deaths (n = 189) caused by lack of prenatal care.
CONCLUSIONS: The most important variables in the model were voluntary HIV testing, the deterrence rate associated with mandatory testing compared with voluntary testing, and the prevalence of HIV infection in women of child-bearing age. At high levels of acceptance of voluntary HIV testing, the benefits of a policy of mandatory testing are minimal and may create the potential harms of avoiding prenatal care to avoid mandatory testing.
A 2-dose intrapartum/newborn nevirapine regimen reduced perinatal human immunodeficiency virus (HIV) transmission in Ugandan women not receiving antenatal antiretroviral therapy (ART). However, it is unknown whether the addition of the 2-dose nevirapine regimen to standard ART would further reduce perinatal HIV transmission.
OBJECTIVE:
To determine whether a 2-dose nevirapine regimen can decrease perinatal transmission of HIV in nonbreastfeeding women receiving standard ART.
DESIGN AND SETTING:
International, blinded, placebo-controlled, phase 3 trial enrolling women between May 1997 and June 2000 at clinical sites providing care for HIV infection throughout the United States, Europe, Brazil, and the Bahamas.
PARTICIPANTS:
A total of 1270 women received nevirapine (n = 642) or placebo (n = 628). Infants were followed up for 6 months to determine HIV-infection status, which was available for 1248 deliveries.
INTERVENTION:
A 200-mg dose of oral nevirapine to women after onset of labor and a 2-mg/kg dose of oral nevirapine to newborns between 48 and 72 hours after birth.
MAIN OUTCOME MEASURES:
Detection of HIV infection in infants and grade 3 and 4 toxic effects in women and newborns.
RESULTS:
After review by the data and safety monitoring board, the trial was stopped early because the overall transmission rates were significantly lower than assumed for the study design. Antenatal ART included zidovudine alone in 23%; combinations without protease inhibitors in 36%; and combinations with protease inhibitors in 41%. Thirty-four percent of women had elective cesarean delivery. No significant safety concerns were identified for women or infants. Detection of HIV infection occurred in 9 (1.4%; 95% confidence interval [CI], 0.6%-2.7%) of 631 nevirapine group deliveries and 10 (1.6%; 95% CI, 0.8%-2.9%) of 617 placebo group deliveries. The 95% CI for the difference in transmission rate (-0.2) between the 2 study arms ranged from -1.5% in favor of nevirapine to 1.2% in favor of placebo (P =.82, Fisher exact test). The transmission rate was higher in women with lower baseline CD4 cell counts and higher delivery HIV RNA levels, but there was no significant difference between treatment arms in any subgroup.
CONCLUSION:
Risk of perinatal HIV transmission was low and no benefit from additional intrapartum/newborn nevirapine was demonstrated when women received prenatal care and antenatal ART, and elective cesarean section was made available.
