Prevention of mother-to-child transmission of HIV in Africa: successes and challenges in scaling-up a nevirapine-based program in Lusaka, Zambia

Stringer, Elizabeth M.; Sinkala, Moses; Stringer, Jeffrey S. A.; Mzyece, Elizabeth; Makuka, Ida; Goldenberg, Robert L.; Kwape, Pascal; Chilufya, Martha; Vermund, Sten H.

doi:10.1097/00002030-200306130-00012

Cited by 129 publications

(102 citation statements)

References 12 publications

(8 reference statements)

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“…However, perinatal transmission of HIV-1 remains a major problem in developing countries because of limited access to antiretroviral therapy (6)(7)(8). In this latter setting, the simple regimen of maternal single-dose intrapartum nevirapine (NVP) and single-dose NVP (sdNVP) for the newborn reduces the risk of mother-to-child HIV-1 transmission (MTCT) by 41% through age 18 mo (9).…”

mentioning

confidence: 99%

Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

Palmer

Boltz

Martinson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

114

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Single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission of HIV-1 can select nevirapine (NVP)-resistant variants, but the frequency, duration, and clinical significance of this resistance is not well defined. We used a sensitive allele-specific PCR assay to assess the emergence and persistence of NVPresistant variants in plasma samples from 22 women with HIV-1 subtype C infection who participated in a study of sdNVP for prevention of mother-to-child transmission of HIV-1. The women were categorized into three groups on the basis of detection of NVP resistance by standard genotype analysis. Group 1 (n ‫؍‬ 6) had NVP resistance detected at 2 and 6 mo after sdNVP, but not at 12 mo. Group 2 (n ‫؍‬ 9) had NVP resistance detected at 2 mo, but not 6 mo. Group 3 (n ‫؍‬ 7) had no NVP resistance detected at any time point. Allele-specific PCR analysis for the two most common NVP resistance mutations (K103N and Y181C) detected NVP-resistant variants in most (16 of 21) samples that were negative for NVP resistance by standard genotype, at levels ranging from 0.1% to 20% 1 yr after treatment. The frequency of NVP-resistant mutations decreased over time, but persisted above predose levels for more than 1 yr in >23% of the women. These findings highlight the urgent need for studies assessing the impact of sdNVP on the efficacy of subsequent antiretroviral therapy containing NVP or other nonnucleoside reverse transcriptase inhibitors.allele-specific PCR ͉ resistance ͉ low-frequency mutants T he treatment of pregnant women with antiretroviral therapy, in combination with zidovudine chemoprophylaxis administered to newborns, has dramatically reduced vertical transmission of HIV in developed countries (1-5). However, perinatal transmission of HIV-1 remains a major problem in developing countries because of limited access to antiretroviral therapy (6-8). In this latter setting, the simple regimen of maternal single-dose intrapartum nevirapine (NVP) and single-dose NVP (sdNVP) for the newborn reduces the risk of mother-to-child HIV-1 transmission (MTCT) by 41% through age 18 mo (9). Moreover, sdNVP has been demonstrated to be more effective than zidovudine chemoprophylaxis alone, and to be equivalent to NVP plus zidovudine in preventing MTCT (9-12). The efficacy of sdNVP in preventing MTCT is attributed to its potent antiviral activity, rapid absorption, placental transfer, and long half-life (13, 14). As a result, its use has been recommended by the World Health Organization as one of several options to reduce MTCT in resource-limited countries [Joint UNAIDS͞WHO press release (2000) (WHO, Geneva)].NVP is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 (15-17). If administered as monotherapy, NVP selects for resistant variants within 1 wk, commonly those variants with the K103N and͞or Y181C mutations in reverse transcriptase, which confer cross-resistance to other approved drugs in the NNRTI class (18)(19)(20). The K103N mutation appears to have little effect on the replicative capacity o...

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confidence: 99%

Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

Palmer

Boltz

Martinson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

137

114

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“…A surprisingly large percentage of women (86%) who tested positive enrolled, and 95% (931/ 985) of those completed the entire protocol. The public health impact on vertical transmission was much higher than previously described [1,[3][4][5][6], with a cumulative intention-to-treat (ITT) analysis transmission rate at 6 months of age of 5.3%. Among women who received HAART until 6 months postpartum, no transmissions occurred beyond 1 month of age.…”

mentioning

confidence: 71%

“…The acceptability of HAART during pregnancy was higher than that of single-dose nevirapine in prior studies [5,6]. Even within the Mozambique health care system, where about 50% of women deliver at home, it was still possible to get women tested for HIV early in the course of pregnancy.…”

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confidence: 87%

Implementing anti-retroviral triple therapy to prevent HIV mother-to-child transmission: a public health approach in resource-limited settings

et al. 2007

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We conducted a retrospective cohort study of HIV-infected pregnant women and their infants enrolled in the DREAM programme for prevention of HIV mother-to-child transmission (MTCT) in Mozambique. All women delivering between May 2002 and December 2005 were offered participation. The programme consisted of the provision of highly active anti-retroviral therapy (HAART) to pregnant women until 6 months postpartum, and formula, clean water, nutritional supplementation, and continuing HAART to mothers if necessary.In Mozambique 1,259 HIV-positive pregnant women were offered participation: 212 (14.4%; CL95% 12.6-16.2) refused, 54 (3.7%; CL95% 2.5-4.9) dropped out during pregnancy, and eight women died. The remaining 985 women participated, giving birth to 958 infants, including 21 sets of twins. An additional 28 babies were stillborn. Spontaneous abortions occurred in 20 cases. Discontinuation of anti-retroviral (ARV) therapy by mothers was 3.7% (54/1,464) before delivery, 1.5% in the first month (23/ 1,464), and 1.5% (22/1,464) between the first and sixth months after delivery. Overall drop-out rates were 5.2% (CL95% 4.6-5.8). Approximately 80% of pregnant women completed the treatment protocol.

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“…In the Lusaka District clinics, PMTCT-related research studies with varying staffing levels and funding were introduced in 13,14 In this study, 3 interventions are studied: implementation of PMTCT-related research, service, or both simultaneously into an ANC. There were no research or service programs unrelated to PMTCT introduced into antenatal care during the time of this study, from July 1997 through July 2004.…”

Section: Hiv Program Implementationmentioning

confidence: 99%

“…The PMTCT service program consisted of universal counseling and voluntary HIV testing with same-day test results and single-dose nevirapine (NVP) offered to HIV-infected pregnant women and their infants. 13 At program introduction, the antenatal nurse-midwives received HIV counseling and testing training and record keeping training. For pregnant women who agreed to HIV testing, the nurse-midwife used a clinicbased laboratory slip to request an HIV test using the same blood specimen as for RPR testing.…”

Section: Service Programsmentioning

confidence: 99%

Do Targeted HIV Programs Improve Overall Care for Pregnant Women?

Potter

Goldenberg

Chao³

et al. 2008

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Prevention of mother-to-child transmission of HIV in Africa: successes and challenges in scaling-up a nevirapine-based program in Lusaka, Zambia

Cited by 129 publications

References 12 publications

Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

Implementing anti-retroviral triple therapy to prevent HIV mother-to-child transmission: a public health approach in resource-limited settings

Do Targeted HIV Programs Improve Overall Care for Pregnant Women?

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