Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana

BACKGROUND: Single-dose nevirapine given to women and infants reduces mother-to-child HIV transmission, but nevirapine resistance develops in a large percentage of women. OBJECTIVE: To determine whether the maternal nevirapine dose could be eliminated in the setting of zidovudine prophylaxis. DESIGN, SETTING, AND PARTICIPANTS: A 2 x 2 factorial, randomized, clinical trial, with a double-blinded peripartum factor designed to assess the equivalence of maternal single-dose nevirapine versus placebo with respect to HIV transmission. A total of 709 HIV-infected pregnant women were randomized from four district hospitals in Botswana, resulting in 694 live first-born infants. HAART was available for women with AIDS. INTERVENTION: All women received a background of zidovudine from 34 weeks' gestation through delivery, and all infants received single-dose nevirapine at birth and zidovudine from birth through 1 month. Women were randomized to receive either single-dose nevirapine or placebo during labor. MAIN OUTCOME MEASURES: The primary endpoint was infant HIV infection by the 1-month visit. RESULTS: Of the 694 infants in this equivalence study, 15 (4.3%) of 345 in the maternal nevirapine arm were HIV infected by 1 month, versus 13 (3.7%) of 349 in the maternal placebo arm (95% confidence interval for difference, -2.4% to 3.8%), meeting pre-determined equivalence criteria. Nevirapine resistance at 1 month postpartum was detected in 45% of a random sample of women who received nevirapine. CONCLUSIONS: In the setting of maternal zidovudine and infant zidovudine plus single-dose nevirapine, infant HIV infection rates were similar whether women received single-dose nevirapine or placebo. This strategy avoids the potential for maternal nevirapine resistance.     

A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers

BACKGROUND: Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy. METHODS: This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis. RESULTS: Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006). CONCLUSION: A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection.     

Universal nevirapine upon presentation in labor to prevent mother-to-child HIV transmission in high prevalence settings

OBJECTIVE: To assess the uptake of and adherence to nevirapine to prevent mother-to-child HIV transmission among women of unknown HIV serostatus presenting in labor. We also assessed preliminary efficacy of the approach. DESIGN: Women of unknown HIV serostatus presenting in labor were offered single-dose nevirapine in a prospective cohort study. Two additional contemporaneous comparison populations were also studied. METHODS: We measured uptake by counting the number of women that accepted enrollment when offered. We measured adherence with cord blood nevirapine assay. We measured preliminary efficacy with HIV DNA polymerase chain reaction of infant blood spots at 4-6 weeks of life. RESULTS: Of 1591 women approached in labor, 634 (40%) took up the intervention and received nevirapine, of whom 185 (29%) were HIV infected. Of 179 cord blood specimens from HIV-exposed infants that could be evaluated, 178 (99.4%) had nevirapine detected. This was higher than the 73 of 98 (74%) adherence rate observed in a comparison cohort in which women self-administered nevirapine before presenting to the labor ward (P < 0.001). Of 145 available infant specimens, 17 (11.7%) showed evidence of infection at 4-6 weeks, compared with 12 of 60 (20%) infants born immediately prior to study commencement whose HIV-infected mothers did not receive nevirapine (P < 0.05). CONCLUSIONS: Nevirapine without HIV testing upon presentation in labor was accepted by two-fifths of women. Because therapy is directly observed, adherence is nearly perfect. Labor ward dosing to enhance nevirapine coverage should be considered as an adjunct to antenatal nevirapine administration for prevention of mother-to-child transmission of HIV.     

Influence of variations in CCL3L1 and CCR5 on tuberculosis in a northwestern Colombian population

We investigated the association of polymorphisms in CCR5, the major human immunodeficiency virus (HIV)-1 coreceptor, and copy number of its potent ligand CCL3L1 with tuberculosis in 298 individuals from Colombia. The CCR5-HHD haplotype, a known genetic determinant of increased susceptibility to HIV-AIDS, and a high copy number of CCL3L1, a known genetic determinant of enhanced CCL3/CCL3L1 chemokine expression, each associated with presence of tuberculosis. Furthermore, CCR5-HHD was associated with higher CCR5 gene and surface expression. These results substantiate the strong link between the pro-inflammatory effects of CCR5 and its ligands with active tuberculosis and suggest that chemokine-chemokine receptor genetic determinants may influence tuberculosis in addition to HIV/AIDS.     

Prevention of mother-to-child transmission of HIV in Africa

HIV infection and mortality rates in African children are astoundingly high. Risk factors for mother-to-child transmission of HIV include maternal plasma viral load and breastfeeding. With regard to the latter, current data indicate that mixed feeding (breastfeeding with other oral foods and liquids) is associated with the greatest risk of transmission. Studies are under way to determine if exclusive breastfeeding with rapid early weaning can reduce transmission rates in the absence of exclusive formula feeding for all infants. Perinatal transmission rates have been dramatically reduced with the use of single-dose nevirapine, but this strategy protects only approximately 50% of infants, and more than 75% of women receiving nevirapine develop a major nevirapine resistance mutation. In developed areas of the world, antiretroviral therapy has reduced perinatal transmission by more than 90% compared with 1993 rates. Improved HIV-related care for HIV-infected women in Africa is needed to reduce rates of HIV infection in children and to prevent maternal mortality. This article summarizes a presentation by Sten H. Vermund, MD, PhD, at the International AIDS Society-USA course in Chicago in May 2004.     

Cost-effectiveness of nevirapine to prevent mother-to-child HIV transmission in eight African countries

BACKGROUND: A comprehensive approach to preventing HIV infection in infants has been recommended, including: (a) preventing HIV in young women, (b) reducing unintended pregnancies among HIV-infected women, (c) preventing vertical transmission (PMTCT), and (d) providing care, treatment, and support to HIV-infected women and their families. Most attention has been given to preventing vertical transmission based on analysis showing nevirapine to be inexpensive and cost-effective. METHODS: The following were determined using data from eight African countries: national program costs and impact on infant infections; reductions in adult HIV prevalence and unintended pregnancies among HIV-infected women that would have equivalent impact on infant HIV infections averted as the nevirapine intervention; and the cost threshold for drugs with greater efficacy than nevirapine yielding an equivalent cost per DALY saved. RESULTS: Average national annual program cost was 4.8 million dollars. There was, per country, an average of 1898 averted infant HIV infections (2517 US dollars per HIV infection and 84 US dollars per DALY averted). Lowering HIV prevalence among women by 1.25% or reducing unintended pregnancy among HIV-infected women by 16% yielded an equivalent reduction in infant cases. An antiretroviral drug with 70% efficacy could cost 152 US dollars and have the same cost per DALY averted as nevirapine at 47% efficacy. CONCLUSIONS: Cost-effectiveness of nevirapine prophylaxis is influenced by health system costs, low client uptake, and poor effectiveness of nevirapine. Small reductions in maternal HIV prevalence or unintended pregnancy by HIV-infected women have equivalent impacts on infant HIV incidence and should be part of an overall strategy to lessen numbers of infant infections.     

Antiretroviral concentrations in breast-feeding infants of women in Botswana receiving antiretroviral treatment

BACKGROUND: The magnitude of infant antiretroviral (ARV) exposure from breast milk is unknown. METHODS: We measured concentrations of nevirapine, lamivudine, and zidovudine in serum and whole breast milk from human immunodeficiency virus type 1 (HIV-1)-infected women in Botswana receiving ARV treatment and serum from their uninfected, breast-feeding infants. RESULTS: Twenty mother-infant pairs were enrolled. Maternal serum concentrations of nevirapine were high (median, 9534 ng/mL at a median of 4 h after nevirapine ingestion). Median breast-milk concentrations of nevirapine, lamivudine, and zidovudine were 0.67, 3.34, and 3.21 times, respectively, those in maternal serum. The median infant serum concentration of nevirapine was 971 ng/mL, at least 40 times the 50% inhibitory concentration and similar to peak concentrations after a single 2-mg/kg dose of nevirapine. The median infant serum concentration of lamivudine was 28 ng/mL, and the median infant serum concentration of zidovudine was 123 ng/mL, but infants were also receiving zidovudine prophylaxis. CONCLUSIONS: HIV-1 inhibitory concentrations of nevirapine are achieved in breast-feeding infants of mothers receiving these ARVs, exposing infants to the potential for beneficial and adverse effects of nevirapine ingestion. Further study is needed to understand the impact of maternal ARV treatment on breast-feeding HIV-1 transmission, infant toxicity, and HIV-1 resistance mutations among infected infants.     

Effect of CCR2 chemokine receptor polymorphism on HIV type 1 mother-to-child transmission and child survival in Western Kenya

The effect of CCR2 polymorphism on HIV-1 mother-to-child transmission and disease progression has not been explored in depth within Africa. As the CCR2-64I variant of this putative HIV coreceptor has been associated with slower progression to AIDS in adults, the current study was undertaken to examine the relationship between CCR2 polymorphism and HIV-1 perinatal transmission and child survival in western Kenya. CCR2 genotype was determined for 445 HIV-seropositive mothers and their infants. The CCR2-64I allele frequency of both mothers and children did not differ by HIV-1 transmission status, regardless of maternal viral load, viral subtype, immune status, or placental malaria status. For infants who acquired HIV perinatally (n = 78), there was no association between CCR2 genotype and viral load upon infection or survival rate over the 2-year follow-up. Our results do not indicate an effect of CCR2-64I on perinatal HIV transmission and survival in Kenyan children.     

A Bayesian Analysis of Prenatal Maternal Factors Predicting Nonadherence to Infant HIV Medication in South Africa

While efforts to prevent mother-to-child transmission of HIV been successful in some districts in South Africa, rates remain unacceptably high in others. This study utilized Bayesian logistic regression to examine maternal-level predictors of adherence to infant nevirapine prophylaxis, including intimate partner violence, maternal adherence, HIV serostatus disclosure reaction, recency of HIV diagnosis, and depression. Women (N = 303) were assessed during pregnancy and 6 weeks postpartum. Maternal adherence to antiretroviral therapy during pregnancy predicted an 80% reduction in the odds of infant nonadherence [OR 0.20, 95% posterior credible interval (.11, .38)], and maternal prenatal depression predicted an increase [OR 1.04, 95% PCI (1.01, 1.08)]. Results suggest that in rural South Africa, failure to provide medication to infants may arise from shared risk factors with maternal nonadherence. Intervening to increase maternal adherence and reduce depression may improve adherence to infant prophylaxis and ultimately reduce vertical transmission rates.     

Genetic analysis of viral variants selected in transmission of human immunodeficiency viruses to newborns

Our previous studies have indicated that HIV transmission from infected mothers to infants occurs with viruses showing rapid kinetics of replication, and either resistance to maternal neutralizing antibodies or sensitivity to enhancing antibodies. The genotypic patterns that result in these and other phenotypic viral characteristics may provide clues to the selection pressures exerted during this mode of transmission. For this reason, DNA sequences of the envelope gene (env) were determined for viral isolates obtained from seropositive women who were mothers of either infected or uninfected infants. Sequences of viruses isolated early in life from the infected newborns were also determined, such that diversity both within isolates and between maternal and infant isolates could be assessed. Among isolates obtained from mothers of uninfected infants, the V3 region of env demonstrated a higher degree of heterogeneity than those from mothers of infected infants. Similar to the viruses obtained from the mothers of infected infants, the infant-derived viral sequences were relatively homogeneous. Finally, the reactivity of maternal plasma with infant-derived HIV isolates, whether via neutralizing or enhancing antibodies, appeared to predict the distribution of viral sequences in the infant isolates. These data suggest that selective pressure on HIV-1 during transmission or growth in the infected infant may be mediated by biologic and/or immunologic processes.     

Serum level of maternal human immunodeficiency virus (HIV) RNA, infant mortality, and vertical transmission of HIV in Zimbabwe

Maternal human immunodeficiency virus (HIV) RNA load, vertical transmission of subtype C HIV, and infant mortality were examined in 251 HIV-seropositive women and their infants in Zimbabwe. Demographic characteristics, health and medical histories, serum HIV RNA loads, and CD4+ lymphocyte counts for mothers were examined by logistic regression analysis to determine significant risk factors and their odds ratios for transmission and infant mortality. Tenfold (1 log10) incremental increases in maternal HIV RNA were associated with a 1.9-fold increase (95% confidence interval [CI], 1.2-2.9) in transmission and a 2.1-fold increase (95% CI, 1.3-3.5) in infant mortality (P<.01). Maternal CD4 cell counts and demographic and medical characteristics were not significant predictors of transmission. However, maternal CD4 cell counts below the median (400/mm3) were significantly associated with infant mortality (P=. 035, Fisher's exact test). The maternal level of serum HIV is an important determinant of vertical transmission and infant mortality in subtype C infection in Zimbabwe.     

Human immunodeficiency virus (HIV) type 1 antibodies in perinatal HIV-1 infection: association with human HIV-1 transmission, infection, and disease progression. For the Women and Infants Transmission Study

Anti -human immunodeficiency virus (HIV) type 1 antibodies in 242 pregnant women and 238 infants were measured at birth and at 1, 2, 4, and 6 months after birth, to estimate their association with perinatal transmission and infant disease progression. Maternal anti-p24 (P=.01) and anti-gp120 (P=.04) antibodies were inversely associated with vertical transmission rates, independent of maternal percentage of CD4 cells, hard drug use, duration of ruptured membranes, serum albumin levels, serum vitamin A levels, and quantitative HIV-1 peripheral mononuclear blood cell culture, but not with maternal plasma immune complex dissociated p24 or HIV-1 RNA copy number, both of which were highly correlated with antibodies. From ages 1-2 months, anti-gp120, -gp41, -p31, and -p66 decayed to a greater extent in infected than in uninfected infants. Infected infants produced anti-p24 antibody by age 2 months, anti-p17 by 4 months, and anti-p41 and anti-gp120 by 6 months. As early as birth, infants with rapid disease progression had lower levels of anti-p24 than did infants whose disease did not rapidly progress, but not independently of HIV-1 RNA levels.     

Polymorphism of Fc receptor IIa for IgG in infants is associated with susceptibility to perinatal HIV-1 infection

OBJECTIVE: To evaluate the effect of polymorphism of the Fc gamma receptor IIa, which is associated with differential human IgG subclass binding, on perinatal HIV-1 transmission. METHODS: Fc gamma RIIa genotype was tested in 448 HIV-seropositive mothers and their infants from a cohort study designed to assess the effect of placental malaria on HIV vertical transmission conducted from 1996 to 2001 in western Kenya. Fc gamma RIIa polymorphism was analyzed for associations with susceptibility to perinatal HIV infection and all-cause child mortality in HIV-positive children. RESULTS: Overall, 20% of infants were perinatally infected with HIV. There was no statistically significant association between maternal genotype and perinatal HIV-1 transmission. However, frequency of the infant Fc gamma RIIa His/His131 genotype was higher in HIV-positive compared with HIV-negative infants (35% and 21%, respectively), whereas the distribution was reversed (15% and 28%, respectively) for infants with the Fc gamma RIIa Arg/Arg131 genotype. Multivariate logistic regression controlling for maternal and infant confounding factors demonstrated that the odds of perinatal HIV infection in infants with the Fc gamma RIIa His/His131 versus Fc gamma RIIa His/Arg131 genotypes were significantly higher (adjusted odds ratio, 2.22; 95% confidence interval, 1.23-4.02; P = 0.009). There was no evidence for an association between HIV-positive child all-cause mortality and Fc gamma RIIa genotype. CONCLUSIONS: This study provides the first evidence that the infant Fc gamma RIIa His/His131 genotype is associated with susceptibility to perinatal HIV-1 transmission and further suggests that there is a dose-response relationship for the effect of the Fc gamma RIIa His131 gene on transmission.     

CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men

OBJECTIVES: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.     

Susceptibility to HIV/AIDS: An Individual Characteristic We Can Measure?

Susceptibility to HIV-1 infections is, beside other factors, determined by individual host genetic variants like HLA class I alleles, CCR5 and CCR2 variants and levels of CCR5 binding chemokines. A new approach to determine the individual risk of acquiring an HIV infection or to estimate the disease progression could now be possible. In a recent study, a significant interindividual and interpopulation difference in the copy number of a segmental duplication encompassing the gene encoding CCL3L1, a potent human immunodeficiency virus-1 (HIV- 1)-suppressive chemokine was found. Possession of a CCL3L1 copy number lower than the population average was associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This could lead to a screening test that identifies people who have a higher or lower susceptibility to HIV/ AIDS, potentially enabling clinicians to adapt treatment regimens. Also, this is particularly important for assessment of the efficacy of a protective vaccine.     

High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis

OBJECTIVES: To determine the natural history of HIV infection following peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes. METHODS: Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% < or = 20%. RESULTS: In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to < or = 20% in 70% and < or = 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months. CONCLUSIONS: MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries.     

Strategies to prevent mother-to-child transmission of HIV

PURPOSE OF REVIEW: This review describes recent advances in the prevention of mother-to-child transmission, focusing on the use of antiretroviral treatment strategies in pregnancy, and discusses the emergence of viral resistance following the use of nevirapine to prevent mother-to-child transmission. RECENT FINDINGS: Mother-to-child transmission has been dramatically reduced in developed countries by the use of antiretroviral treatment and avoidance of breastfeeding. Highly active antiretroviral therapy use in pregnancy is recommended for women who require ongoing treatment, and, where available, is also very effective in reducing mother-to-child transmission in women with higher CD4 counts. The addition of a maternal and infant nevirapine dose to antenatal zidovudine can reduce transmission to below 5%, approximately half the transmission rate that can be achieved by single-dose nevirapine alone. The emergence of resistant virus following nevirapine use is a concern, occurring in up to 60% of mothers and 50% of infants following a single dose. Addition of zidovudine and lamivudine for 4-7 days postpartum can reduce the risk of resistance to 10%. SUMMARY: There is broad consensus on an approach to preventing mother-to-child transmission, which provides antiretroviral treatment in pregnancy and beyond to those women who need it, and an effective prophylactic regimen for those who do not yet need treatment, These regimens include highly active antiretroviral therapy, where available, a zidovudine-plus-nevirapine regimen in other settings, or nevirapine alone where this is all that is possible. More work is needed on the impact of nevirapine resistance and on reducing breast-milk transmission.     

A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006)

OBJECTIVE: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. DESIGN: An open label phase I/II study. SETTING: Tertiary care hospital, Kampala, Uganda. PATIENTS AND INTERVENTIONS: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. OUTCOMES: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. RESULTS: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. CONCLUSION: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.