Epidemiology and Social
Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana
Shapiro, Roger La,b,c; Thior, Iboub,c; Gilbert, Peter Bd; Lockman, Shahinb,c,e; Wester, Carolynb,c; Smeaton, Laura Mf; Stevens, Lisab,c; Heymann, S Jodyc,g; Ndung'u, Thumbib,c; Gaseitsiwe, Simanic; Novitsky, Vladimirb,c; Makhema, Josephb,c; Lagakos, Stephenf; Essex, Maxb,c
From the aDivision of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
bDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
cBotswana-Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education, Gaborone, Botswana
dDepartment of Biostatistics, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
eInfectious Disease Unit, Brigham and Women's Hospital, Boston, Massachusetts, USA
fDepartment of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
gDepartment of Society, Human Development and Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Received 18 November, 2005
Revised 23 January, 2006
Accepted 23 February, 2006
Correspondence to M. Essex, Department of Immunology and Infectious Diseases, Harvard School of Public Health, FXB 402, 651 Huntington Avenue, Boston, MA 02115, USA. Tel: +1 617 432 0975; fax: +1 617 739 8348; e-mail: email@example.com
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 × 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.
Mother-to-child HIV transmission (MTCT) remains a serious problem in developing countries, where as many as 700 000 infants become HIV infected annually . Short courses of maternal and infant zidovudine or single doses of maternal and infant nevirapine can reduce antepartum and peripartum MTCT rates to 5-15%, depending upon the duration of zidovudine prophylaxis and whether breastfeeding also occurs [2-5]. The combined use of these strategies lowered MTCT rates to 2% (in the absence of breastfeeding) in a randomized trial in Thailand . However, nevirapine-associated resistance mutations are detected in 15-67% of women following single-dose nevirapine [7-11], limiting enthusiasm for this intervention.
Thirty-seven percent of pregnant women test HIV positive at surveillance sites in Botswana . A zidovudine-based MTCT prevention program was established by the government in 1999. In this setting, we conducted a randomized clinical trial to evaluate strategies to prevent peripartum and breastfeeding MTCT. This article presents results for the redesigned peripartum intervention, which assessed the equivalence of maternal nevirapine versus placebo in the setting of additional maternal and infant prophylaxis. Results from the original peripartum study, which terminated before complete enrollment, will be presented elsewhere.
We conducted a partially double-blind, randomized trial among HIV-infected women and their infants in Botswana. The trial used a 2 × 2 factorial design comparing both peripartum and postpartum strategies to prevent MTCT. The postpartum factor compared extended infant zidovudine prophylaxis during breastfeeding versus formula feeding . For the peripartum intervention, all women received a background of zidovudine prophylaxis from 34 weeks' gestation until delivery, and all infants received zidovudine syrup prophylaxis from birth until 1 month of age. A study was originally designed to assess the superiority of single-dose nevirapine given to both women and infants as compared with placebo, when added to the maternal and infant zidovudine prophylaxis. However, in response to efficacy data from Thailand , our independent Data Safety and Monitoring Board recommended that this peripartum superiority study be terminated after 17 months of enrollment. On 12 August 2002, the present study was initiated, where all infants received open-label nevirapine immediately following birth and only maternal single-dose nevirapine was compared with placebo. Its objective was to assess, on a background of maternal and infant zidovudine, the equivalence of maternal single-dose nevirapine versus placebo with respect to HIV transmission.
The study and amendments were approved by ethics committees at the Botswana Health Research Unit and the Harvard School of Public Health. The study was performed in accordance with regulations of the Department of Health and Human Services for the protection of human research subjects.
Patient population, zidovudine treatment, and follow up
Pregnant women confirmed to be HIV infected were referred to study sites at the district hospitals in one city, one town, and two large villages in southern Botswana, and enrolled between 20 June 2002 and 29 October 2003 (those enrolled before 12 August 2002 were re-consented for the new study design). Women eligible for inclusion were between 33 and 35 weeks' gestation, had a positive HIV-1 ELISA on two separate samples, were ≥ 18 years old, had hemoglobin ≥ 8 g/dl, absolute neutrophil count ≥ 1000 cells/μl, alanine amino transferase (ALT) and aspartate amino transferase (AST) ≤ 10 times upper limit of normal, and creatinine ≤ 1.5 mg/dL, did not have known intolerance to zidovudine or nevirapine; and provided written informed consent.
All women received zidovudine 300 mg twice daily except those receiving HAART (see HAART Availability). Baseline CD4 cell count, HIV-1 RNA viral load, and hematology testing were performed. Zidovudine adherence was monitored weekly until delivery.
Women received additional 300-mg doses of zidovudine to take every 3 h during labor, and hematology was tested at delivery. Infants were evaluated at birth by physical exam, complete blood count, liver function testing (if jaundiced), and HIV-1 DNA PCR. All infants began zidovudine 4 mg/kg 12 h immediately following birth.
At 1 month postpartum, maternal plasma was stored and HIV-1 resistance testing was later performed in a simple random sample of women who received nevirapine. Infant 1-month evaluations included physical examination; feeding, health, and zidovudine adherence questionnaires; complete blood count; creatinine and liver function testing; and HIV-1 DNA PCR.
Beginning in October 2002, 2 months after the start of the study, HAART (nevirapine, zidovudine, plus lamivudine) became available through the Botswana government to women with CD4 cell counts < 200 cells/μl or AIDS-defining illness. Women participating in the study who met these criteria at any stage of study participation were offered HAART. Study participants who started HAART prior to delivery did not receive single-dose nevirapine or placebo at labor onset. Analyses were performed both including and excluding infants whose mothers received HAART before delivery. Infants confirmed HIV-1 infected were also offered HAART.
Randomization, blinding, and nevirapine study treatment
Randomization occurred at 34 weeks' gestation. Maternal randomization to a single dose of 200 mg nevirapine or placebo occurred centrally, stratified by site, using permuted blocks. Nevirapine or placebo tablets were provided at study entry in a double-blinded manner, to be self-administered at the onset of labor. Additional blinded doses of nevirapine or placebo were available on the maternity ward for women who did not take the initial dose, who vomited within 30 min of ingestion, or for cases of persistent labor (> 48 h after initial dose). All infants were provided 6.0 mg of nevirapine syrup immediately after birth, except for premature infants (weighing < 2 kg and born < 35 weeks' gestation) who received 3.0 mg of nevirapine syrup.
Nevirapine tablets and syrup, and placebo tablets, were provided by Boehringer Ingelheim and were repackaged at the pharmacy of Children's Hospital, Boston. Zidovudine tablets and syrup were provided by GlaxoSmithKline.
The primary endpoint was infant HIV infection by the 1-month visit, defined as more than one positive DNA PCR test on different blood samples with at least one performed on a sample collected by 45 days of age. One infant with a single positive PCR who died at 37 days was classified as infected. Infants were considered HIV infected at birth if a sample collected within 15 days of birth was PCR positive.
Infant HIV infection was detected by qualitative DNA PCR using the Amplicor HIV-1 test (Roche Diagnostic Systems, New Jersey, USA). Maternal plasma viral load was quantified (lower detection limit 400 copies/ml) using the automated COBAS Amplicor HIV-1 Monitor Test v.1.5 (Roche Molecular Systems Inc., New Jersey, USA). Genotyping was performed on plasma HIV using ViroSeq HIV-1 Genotyping System (Applied Biosystems, Foster City, California, USA). Nevirapine concentrations in maternal plasma were measured at the University of California, San Diego, by validated reversed phase high-pressure liquid chromatography assays using UV detection.
The study was designed to assess equivalence of maternal placebo to maternal single-dose nevirapine for infant HIV infection. The study was anticipated to enroll and randomize 709 women, based upon planned accrual for the feeding study. Equivalence was pre-determined as the lower limit of the two-sided 95% confidence interval (CI) for the risk difference (nevirapine-placebo) being greater than -3.1%. Critical significance levels to evaluate early differences between nevirapine and placebo were computed using the Lan-DeMets implementation of the O'Brien-Fleming two-sided boundaries . Analyses included all first-born live-born infants (including those with mothers receiving HAART) except where noted. Infants were analyzed by assigned treatment regardless of drugs received by mother or infant or feeding practices. The primary analysis compared rates of HIV infection with a Fisher's exact test. Exact 95% CI for rate differences were computed by inverting two unconditional one-sided exact tests. Zelen's exact test was used for assessing statistical interaction .
Logistic regression models assessed maternal and infant characteristics as predictors of transmission. These models were also used for exploratory analyses, and to control for baseline and labor risk factors. Exact tests and confidence intervals were implemented with StatXact 7.0 software. All reported P values are two-sided and not adjusted for multiple testing.
Of 9031 pregnant women screened for the equivalence study, 3030 (33.6%) were HIV infected, and 709 enrolled in the study. The majority of women who were HIV infected but did not enroll were ineligible because they presented after 34 weeks' gestation, had a laboratory ineligibility, or did not plan to remain in the study area; approximately 8% who were eligible declined participation in the study. Fig. 1 summarizes enrollment, loss to follow-up, and HIV testing through 1 month. HIV status by birth and 1 month was known for 681 (98%) and 656 (94.5%) of the 694 live-born infants in the study, respectively.
Characteristics of women and infants
Baseline characteristics of women and infants were similar by randomization arm (Table 1), and by feeding strategy . Among women who delivered and were not on HAART, 582 (91.9%) of 633 reported ingestion and retention of nevirapine or placebo. Pharmacologic testing in a random sample of 96 women in the nevirapine arm who self-reported receipt of study medication found detectable nevirapine concentrations (≥ 43 ng/ml) in the blood of 95 (99%), supporting self-reported results. Only 5% of women delivered within 1 h of taking nevirapine or placebo. Of 694 live-born infants, 681 (98%) received nevirapine or placebo.
Infant mortality by 1 month did not differ significantly between arms: seven in the maternal nevirapine arm versus 13 in the maternal placebo arm (P = 0.26); four infant deaths in the maternal nevirapine arm and three deaths in the maternal placebo arm were considered 'possibly related to HIV' upon blinded review, and the remainder were either unrelated or unknown. Death or loss-to-follow-up after the birth PCR resulting in a missing 1-month PCR also did not differ between arms: seven in the maternal nevirapine arm versus nine in the maternal placebo arm (P = 0.80). HAART was started before delivery in 71 (10.1%) of 704 women who delivered: 40 in the nevirapine arm, and 31 in the placebo arm. All of these women started HAART during pregnancy, the majority in the third trimester; more than half had started before randomization (27 in the nevirapine arm, 14 in the placebo arm).
Among 694 live births, 28 (4.0%) were HIV infected by 1 month, 21 (75%) of whom were HIV infected at the birth visit PCR (Table 2). Birth PCRs were performed within 4 days of birth for 98% of the infants with an available test, and for 95% of those with a positive birth PCR. All infants HIV infected at birth had two or more positive PCR tests. Six of the seven infants whose PCR results became positive between birth and 1 month had two or more positive PCR tests, and one infant had a single PCR-positive result at day 30 and died at day 37.
At the 1-month primary endpoint, 15 (4.3%) of 345 in the maternal nevirapine arm were HIV infected, compared with 13 (3.7%) of 349 in the maternal placebo arm (95% CI for difference, -2.4% to 3.8%), meeting the pre-determined criterion for equivalence. No interaction was detected between the peripartum intervention and feeding strategy (P = 1.0). Excluding the live-born infants whose mothers received HAART before delivery, 14 (4.6%) of 305 in the maternal nevirapine arm were HIV infected by 1 month, compared with 12 (3.8%) of 319 in the maternal placebo arm (P = 0.69; 95% CI for difference, -2.4% to 4.2%), also meeting the equivalence criterion. An exploratory analysis of infants who became infected between birth and 1 month of age also revealed no transmission difference between groups: two infections in the maternal nevirapine arm versus five in the placebo arm (P = 0.45).
Risk factors for transmission and maternal resistance
In univariate analyses, higher baseline HIV-1 RNA and lower baseline CD4 cell count were associated with 1-month transmission (Table 3). Adjustment for these covariates did not qualitatively change any treatment arm comparisons. In a multivariate model, higher baseline HIV-1 RNA was the only significant independent predictor of transmission.
Nevirapine resistance mutations were observed in 69 of 155 (45%) 1-month postpartum samples from randomly selected women who received single-dose nevirapine (Table 4). No baseline nevirapine mutations were detected in previous studies of 122 antiretroviral-naive adults in Botswana [16,17].
Maternal and infant safety
Toxicity rates were low in both women and infants. Between study entry and 3 months after delivery, 20 (2.8%) women had a serious or life-threatening event: one event was determined to be possibly related to zidovudine (anemia) and two events were possibly related to single-dose nevirapine or placebo (one rash and one abnormal liver function test, both in the placebo arm). Among infants, 12 (1.7%) discontinued zidovudine before 30 days of age due to protocol-defined toxicities (most commonly anemia or neutropenia). Five (0.7%) of 694 live-born infants had a serious or life-threatening event possibly related to single-dose nevirapine. Four were rashes regarded as serious, and one was bilirubin elevation with jaundice treated as neonatal jaundice. Two were hospitalized (one with vesicular rash and fever, and one with jaundice), but none died.
This equivalence study found that avoiding maternal single-dose nevirapine exposure and only adding infant single-dose nevirapine to a background of maternal and infant zidovudine was similar to providing single-dose nevirapine to both mothers and infants. This strategy allows women who receive adequate antenatal zidovudine to be spared exposure to single-dose nevirapine, and to avoid the risk of developing resistance to nevirapine.
The finding that the two groups were equivalent suggests that the main contribution of single-dose nevirapine when added to zidovudine may be to provide additional post-exposure prophylaxis to infants, and that the maternal nevirapine dose can be avoided without compromising efficacy. Because all infants received nevirapine and zidovudine prophylaxis, the amount of protection afforded by infant nevirapine could not be determined from the results of our study. However, the importance of nevirapine for post-exposure prophylaxis is supported by the very low transmission rates in our study, and by a comparison across two studies of infants who received nevirapine prophylaxis in Malawi. Although these studies were not intended to be compared directly, similar early MTCT rates were found whether mothers presented in time to receive the maternal dose of single-dose nevirapine or not [18,19]. These studies also demonstrated lower rates of nevirapine resistance among HIV-infected infants when maternal nevirapine was avoided and when zidovudine was added to single-dose nevirapine for infant post-exposure prophylaxis .
Our results may also be compared to a randomized study in Thailand , that found that avoiding the infant nevirapine dose was possible in the setting of background zidovudine and maternal nevirapine. In Thailand, maternal nevirapine added protection to the background zidovudine, likely by providing additional infant prophylaxis during labor, delivery, and after birth. Because nevirapine readily crosses the placenta, infant blood levels at birth are similar to those achieved by direct dosing of infants, provided the maternal dose is given at least 2 h before delivery [21,22]. Seen in this context, the results of the Thailand and Botswana studies are not contradictory, but differ only in the timing of when prophylaxis was provided to the infants (pre- and post-exposure starting in utero or post-exposure starting at birth). Our hypothesis that nevirapine primarily contributes to MTCT prevention by adding post-exposure prophylaxis was not directly studied in Thailand, but it is consistent with the findings of both studies.
This study was part of a 2 × 2 factorial trial that also evaluated infant feeding strategies. Although recent evidence suggests that maternal single-dose nevirapine may reduce breast milk HIV-1 RNA throughout the first month postpartum , in the setting of 1 month of infant zidovudine prophylaxis we did not detect a difference in MTCT rates by feeding strategy. Because no interaction was detected between the two factors of our trial, we have presented the results independent of the feeding trial. We chose the 1-month transmission rate as our primary endpoint (rather than the transmission rate between birth and 1 month) to avoid bias from random differences in the in utero infection rate, which may remove the infants at highest risk of infection from the pool of infants at risk in the peripartum period. Infections between birth and 1 month also did not differ by study arm, although the total number of such infections was small.
HAART was made available to women in our study for ethical reasons, and this makes the efficacy of our intervention difficult to assess for women with lower CD4 cell counts. Although only 10% of all women received HAART before delivery, this group included about 60% of the women with baseline CD4 cell counts < 200 cells/μl. Two (2.8%) women transmitted HIV among the 71 who received HAART (both started HAART near delivery and had detectable delivery HIV-1 RNA), compared with four (8.3%) of 48 women with baseline CD4 counts ≤ 200 cells/μl who did not receive HAART. Although this difference is not statistically significant, it suggests that HAART may have lowered the MTCT rate among the 71 women who received it, preventing approximately four additional transmissions and modestly lowering overall transmission in this period from approximately 4.6% to 4.0%. This estimate suggests that HAART may have reduced the number of transmissions in our study, but it did not do so preferentially; HAART use did not differ by randomization arm, and equivalence of the two groups was established in infants whose mothers did not receive HAART.
The lower-than-expected transmission rate in the peripartum period may have limited our ability to detect an effect from the nevirapine intervention. HAART availability may have contributed to this limitation, as the 71 women who received HAART before delivery did not receive the intervention, and otherwise would have been among those at highest risk to transmit HIV to their infants. In addition, 75% of transmissions in this study occurred in utero, before the nevirapine intervention could impact transmission rates. A high percentage of in utero transmissions is consistent with previous data for HIV-1 subtype C , but interpretation is limited because our actual in utero infection rate (3%) was lower than other studies in Africa where antenatal prophylaxis regimens differed or were not used [5,10,18]. Therefore, the low peripartum transmission rates may simply reflect the effectiveness of the antenatal and intrapartum zidovudine provided to all women and the single-dose nevirapine and zidovudine provided to infants. We cannot rule out the possibility that benefit from the maternal nevirapine dose might be observed in a larger study where more peripartum transmissions are evaluable.
Toxicity rates were low for both mothers and infants. For women, the most important potential long-term safety concern was that 45% receiving active nevirapine had genotypic mutations associated with nevirapine resistance at 1 month postpartum, which is consistent with other studies from southern Africa, where subtype C predominates [10,11].
In summary, we demonstrated that maternal single-dose nevirapine may not be needed to reduce MTCT in the setting of maternal and infant zidovudine prophylaxis and infant single-dose nevirapine. Transmission rates at 1 month of age were among the lowest ever reported from Africa. HAART availability probably contributed to this low transmission rate, as well as administration of zidovudine from 34 weeks' gestation in mothers and for 1 month in all infants. It is important to note that our findings may not be transferable to women with lower CD4 cell counts, or women who have not received zidovudine during the last 4-6 weeks of pregnancy. In the absence of antiretroviral prophylaxis during pregnancy, maternal single-dose nevirapine may continue to play an important role in MTCT prevention programs. However, in the setting of antenatal zidovudine, and HAART availability for women who require it for their own health, our study suggests a strategy that spares women exposure to single-dose nevirapine. If confirmed in other settings, these findings have the capacity to prevent maternal resistance mutations and take on particular importance as we enter an era of wider HAART availability.
We are indebted to the patients who participated in the Mashi Study, and thank the Mashi Study team, that, in addition to the authors of this paper, included: Molepolole Site; Chuka Anude, Jonas Chanda, Lillian Makori, Janet Banno Moorad, Taolo Agnes Modise, Tholakele Moyo, Dipotso Arbi, Matseo Malamba, Kgomotso Koloi, Lerato Dube, Tumisang Mmolotsi, Setho Babitseng, Dorcus Mere; Mochudi Site; Jenny Boyle, Jane Magetse, Tumalano Sekoto, Venice Modikwa, Lebopo Garebatho, Margaret Tsuro, Merriam Sesinyi, Kabo Kelebalekgosi; Lobatse Site; Zegabriel Tedla, Gloria Mayondi, Ntukunu Makubate, Keatile Sebinang, Lesedi Tsalaile, Boniny Tsule, Irene Thebeetsile, Jessica Setswalo, Irene Leteane, Oarabile Makgabana; Gaborone Site; Mpho Mogodi, Anchilla Owor, Innocent Hove, Aida Asmelash, Tebogo Kakhu, Phana Ramalepa, Joyce Lubinda, S'khatele Ndebele, Florence Modise, Chenesani Bohule, Malegogo Ntshimane.
We thank the members of the Data Safety and Monitoring Board (Unity Dow, Richard Gelber, David Katzenstein, Bernard Lo, Alexander Mushi, Christine Mwangi, and Richard Whitley). We also thank Ria Madison, Tlhongbotho Masoloko, Mary Fran McLane, Monty Montano, Sui Yuan Chang, Enoch Sepako, Gaseene Sebetso, Tapologo Nkoane, Betsi Naledi Bome, Fatima Chand, Ann Marie Reich, Molly Pretorius Holme, Kenneth Onyait, Sandi Johnson, Sarah Yates, Mpho Mmelesi, Kelesitsi Phiri, Carol Suckow, Al Patterson, Rocco Anzaldi, Onalenna Ntogwa, Reginah Molefe, Tlhalefo Maotwe, Best Mafoko, Amelia Sanders, Keafiwa Maswere, Julia Setimela, Lynne Mofenson, Marc Lallemant, Gonzague Jourdain, Jack Moye, and Anne Willoughby.
We thank the Botswana Ministry of Health for providing nursing and driver support, and the antiretroviral agents and monitoring for women and infants on HAART; the administration, and maternity ward and MCH staff at the Scottish Livingstone Hospital, Deborah Retief Memorial Hospital, Athlone Hospital, and Princess Marina Hospital. We thank the District Health Teams and DHT Clinics in Molepolole, Mochudi, Lobatse and Gaborone. We also thank the Central Medical Store and Medswana.
Sponsorship: Supported by a grant from the National Institutes of Health, NICHD (R01 HD37793); by Boehringer Ingelheim (for nevirapine); and by GlaxoSmithKline (for zidovudine). The Fogarty International Center grant TW00004 supported several of the trainees who were involved in this study.
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Additional authors: Kenneth McIntosh, Trevor Peter, Soyeon Kim, Erik van Widenfelt, Claire Moffat, Patrick Ndase, Peter Arimi, Poloko Kebaabetswe, Patson Mazonde, Tun-Hou Lee, and Richard Marlink.
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Journal of Clinical Pharmacy and Therapeutics
Systematic review of the efficacy of antiretroviral therapies for reducing the risk of mother-to-child transmission of HIV infection
Journal of Clinical Pharmacy and Therapeutics, 32(3):
Clinical Infectious DiseasesEfficacy and Safety of 1-Month Postpartum Zidovudine-Didanosine to Prevent HIV-Resistance Mutations after Intrapartum Single-Dose NevirapineClinical Infectious Diseases
Clinical Infectious DiseasesNevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single-Dose NevirapineClinical Infectious Diseases
Plos OneEffectiveness of Multidrug Antiretroviral Regimens to Prevent Mother-to-Child Transmission of HIV-1 in Routine Public Health Services in CameroonPlos One
American Journal of Obstetrics and GynecologyInternational recommendations on antiretroviral drugs for treatment of HIV-infected women and prevention of mother-to-child HIV transmission in resource-limited settings: 2006 updateAmerican Journal of Obstetrics and Gynecology
AIDS Research and Human RetrovirusesEfficacy of antiretroviral drugs in reducing mother-to-child transmission of HIV in Africa: A meta-analysis of published clinical trialsAIDS Research and Human Retroviruses
AIDS Research and Human RetrovirusesIntrapartum Tenofovir and Emtricitabine Reduces Low-Concentration Drug Resistance Selected by Single-Dose Nevirapine for Perinatal HIV PreventionAIDS Research and Human Retroviruses
AIDS Research and Human RetrovirusesUltrasensitive Detection of Minor Drug-Resistant Variants for HIV After Nevirapine Exposure Using Allele-Specific PCR: Clinical SignificanceAIDS Research and Human Retroviruses
Presse MedicaleThe challenges of preventing mother-to-child transmission of HIV in AfricaPresse Medicale
Clinical Infectious DiseasesAnother Milestone in Minimizing Risks to Mothers Exposed to Single-Dose Nevirapine for Prevention of Vertical Transmission of HIV-1 to Infants: What Next?Clinical Infectious Diseases
New England Journal of Medicine
Response to antiretroviral therapy after a single, peripartum dose of nevirapine
New England Journal of Medicine, 356(2):
Antiviral ResearchUpdate on antiretroviral therapy in paediatricsAntiviral Research
Plos OneHIV-1 Subtype C-Infected Individuals Maintaining High Viral Load as Potential Targets for the "Test-and-Treat'' Approach to Reduce HIV TransmissionPlos One
AIDS Research and Human RetrovirusesTemporal Reduction of HIV Type 1 Viral Load in Breast Milk by Single-Dose Nevirapine during Prevention of MTCTAIDS Research and Human Retroviruses
Paediatric Respiratory ReviewsTuberculosis and human immunodeficiency virus co-infection in children: management challengesPaediatric Respiratory Reviews
AIDS Research and Human RetrovirusesDetection of HIV type 1 gag-specific CD4(+) T cell responses in acutely infected infantsAIDS Research and Human Retroviruses
Clinical Infectious DiseasesTime to undetectable viral load after highly active antiretroviral therapy initiation among HIV-infected pregnant womenClinical Infectious Diseases
Jama-Journal of the American Medical Association
Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana - A randomized trial: The Mashi study
Jama-Journal of the American Medical Association, 296(7):
LancetReduction of HIV-1 drug resistance after intrapartum single-dose nevirapineLancet
Journal of Infectious DiseasesInfant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and HIV-uninfected women in BotswanaJournal of Infectious Diseases
LancetSingle-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: an open-label randomised trialLancet
Clinical Infectious DiseasesPrevention in Neglected Subpopulations: Prevention of Mother-to-Child Transmission of HIV InfectionClinical Infectious Diseases
Hematologic and hepatic toxicities associated with antenatal and postnatal exposure to maternal highly active antiretroviral therapy among infants
Journal of Antimicrobial ChemotherapyOnce- or twice-daily dosing of nevirapine in HIV-infected adults: a population pharmacokinetics approachJournal of Antimicrobial Chemotherapy
JAIDS Journal of Acquired Immune Deficiency SyndromesIndependent Effects of Nevirapine Prophylaxis and HIV-1 RNA Suppression in Breast Milk on Early Perinatal HIV-1 TransmissionJAIDS Journal of Acquired Immune Deficiency Syndromes
HIV; AIDS; vertical transmission; Botswana; Africa; nevirapine; zidovudine
© 2006 Lippincott Williams & Wilkins, Inc.
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