Articles tagged as "Preventing HIV infection in children"

Antiretroviral treatment

Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, Chand F, Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van Widenfelt E, Mazhani L, Novitsky V, Lagakos S, Essex M. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 2007;356:135-47.http://content.nejm.org/cgi/content/full/356/2/135

Photo credit: AVECC/H. Vincent
Photo credit: AVECC/H. Vincent
A single dose of nevirapine during labour reduces perinatal transmission of HIV-1 but often leads to viral nevirapine resistance mutations in mothers and infants. Lockman and colleagues studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan–Meier method. Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment. The authors conclude that women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine.

Editors’ note: These study results are encouraging because they suggest that the risk that single dose nevirapine will compromise subsequent treatment success for women can be reduced if antiretroviral treatment is started at least 6 months after childbirth. If confirmed by similar studies, these findings could have important implications for decisions about when to treat women post-partum; however, combining drugs for prevention of mother-to-child transmission would also reduce the risk of resistance and keep treatment options open for women.


Garcia R, Badaro R, Netto EM, Silva M, Amorin FS, Ramos A, Vaida F, Brites C, Schooley RT. Cross-sectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients. AIDS Res Hum Retroviruses 2006;22:1248-52.

Antiretroviral therapy success is highly dependent on the ability of the patient to fully adhere to the prescribed treatment regimen. Garcia and colleagues present the results of a cross-sectional study that evaluates the predictive value of a self-administered questionnaire on adherence to antiretroviral therapy (ART). Study participants were interviewed using a 36-item Patient Medication Adherence Questionnaire (PMAQ) designed to assess knowledge about ART, motivation to adhere to treatment, and behavioural skills. Plasma HIV-1 RNA levels were correlated with the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were receiving their initial ART regimen. Of the remaining patients, 39 (21%) and 61 (34%) were on a second or additional ART regimen, respectively. An undetectable viral load was documented in 47/62 (76%) patients on their first regimen who reported missing medication on less than 4 days in the last 3 months. The Patient Medication Adherence Questionnaire had a higher predictive value of plasma viral suppression for patients in the initial regimen than for patients in salvage therapy. The overall predictive value of the Patient Medication Adherence Questionnaire to identify adherence was 74%, and 59% for nonadherence, with an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the concept of ART, 80% were failing or had previously failed the ART. Of 35 patients with doubts about their HIV status or skeptical of the benefits of ART, 29 (84%) were nonadherent. Despite the positive predictive value of PMAQ in identifying adherence, self-reported adherence is not a sufficiently precise predictor of treatment success to substitute for viral load monitoring. On the other hand, the use of such an instrument to identify factors associated with nonadherence provides an excellent opportunity to apply early intervention designed to specifically address factors that might be contributing to the lack of adherence prior to regimen failure.

Editors’ note: The relatively short administration time of this questionnaire which could assist in tailoring adherence counselling, suggests that it should be validated for use as a screening tool in other settings where patients are literate.
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Infant Outcomes

Szyld EG, Warley EM, Freimanis L, Gonin R, Cahn PE, Calvet GA, Duarte G, Melo VH, Read JS; for the NISDI Perinatal Study Group. Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth. AIDS 2006;20:2345-53.

Szyld determined the relationship between maternal antiretroviral regimens during pregnancy and adverse infant outcomes in a prospective cohort study of HIV-1-infected women and their infants (NISDI Perinatal Study). Data were analysed from 681 women receiving at least one antiretroviral drug [in order of increasing complexity: 1 or 2 nucleoside reverse transcriptase inhibitors (1-2 NRTI), 2 NRTI plus 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (HAART/NNRTI), or 2 NRTI plus 1 PI (HAART/PI)] for at least 28 days during pregnancy, and who delivered live born, singleton infants with known birth weight and gestational age by 1 March 2005. Multivariable logistic regression modelling was used to assess the relationship of maternal ART with low birth weight and with preterm birth. The incidence of low birth weight and preterm birth, respectively, was 9.6% and 7.4% (1-2 NRTI), 7.4% and 5.8% (HAART/NNRTI), and 16.7% and 10.6% (HAART/PI). There was no statistically significant increased risk of low birth weight (OR 1.5, 95%CI 0.7-3.2) or preterm birth (OR 1.1, 95%CI 0.5-2.8) among women who received HAART/PI compared with women receiving 1-2 NRTI. The authors conclude that among a population of HIV-1-infected women in Latin America and the Caribbean, maternal receipt of PI-containing ART regimens during pregnancy was not associated with a statistically significant increase in risk of low birth weight or preterm birth.


Leroy V, Sakarovitch C, Viho I, Becquet R, Ekouevi DK, Bequet L, Rouet F, Dabis F, Timite-Konan M; the ANRS 1201/1202 Ditrame Plus Study Group. Acceptability of formula-feeding to prevent HIV postnatal transmission, Abidjan, Cote d'Ivoire: ANRS 1201/1202 Ditrame Plus Study. J Acquir Immune Defic Syndr 2006 Oct 5 [Epub ahead of print].

Leroy and colleagues described the maternal acceptability of formula-feeding proposed to reduce postnatal HIV transmission in Abidjan, Cote d'Ivoire. Each consenting HIV-infected pregnant woman, age at least 18 years, who received a perinatal antiretroviral prophylaxis was eligible. Two hierarchical infant-feeding options were proposed antenatally: exclusive formula-feeding or short-term exclusive breast-feeding. Formula-feeding was provided free up to age 9 months. Determinants of acceptability were analysed using logistic regression. Formula-feeding failure was defined as having breast-fed one's child at least once. Between March 2001 and March 2003, 580 women delivered: 97% expressed their infant-feeding choice before delivery; 53% chose formula-feeding. Significant prenatal determinants for refusing formula-feeding were: living with her partner, being Muslim, having a low educational level, being followed in one of the study sites, having not disclosed her HIV status, and having been included within the first 6 months of the project. Among the 295 mothers who formula-fed, the Kaplan-Meier probability of success of the formula-feeding option was 93.6% at Day 2 (95%CI 90.7-96.3) and 84.2% at 12 months (95% CI 79.9-88.5): 46 of 295 (15.6%) women breast-fed at least once, of whom 41% temporarily practiced mixed-feeding at Day 2 because of social stigma or newborn poor health. The authors conclude that in settings with general access to clean water, structured antenatal counselling, and sustained provision of free formula, slightly over half of HIV-infected women chose to artificially feed their newborn infant. Low mixed-feeding rates were observed. This social acceptability must be balanced with mother-child long-term health outcomes to guide safe recommendations on infant-feeding among HIV-infected women in African urban settings.

Editors’ notes: Both these studies are encouraging, the first because it increases the treatment options for pregnant women on antiretroviral therapy and the second because it shows that formula feeding to prevent HIV transmission can be achieved in a high proportion of women who opt to formula feed after counselling - when the formula is free, the water is safe and the social environment is supportive.

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Infant Feeding

Orne-Gliemann J, Mukotekwa T, et al. Community-based assessment of infant feeding practices within a programme for prevention of mother-to-child HIV transmission in rural Zimbabwe. Public Health Nutr 2006;9:563-69.

Orne-Gliemann and colleagues describe the infant feeding practices and attitudes of women who used prevention of mother-to-child transmission of HIV (PMTCT) services in rural Zimbabwe. They conducted a cross-sectional study including structured interviews and focus group discussions between June 2003 and February 2004 in Murambinda Mission Hospital (Buhera District, Manicaland Province), the first site offering PMTCT services in rural Zimbabwe. The interviews targeted HIV-infected and HIV-negative women who received prenatal HIV counselling and testing and minimal infant feeding counselling, and who delivered between 15 August 2001 and 15 February 2003. Focus groups were conducted among young and elderly men and women. Overall, 71 HIV-infected and 93 HIV-negative mothers were interviewed in clinics or at home. Most infants (97%) had ever been breast-fed. HIV-negative mothers introduced fluids/foods other than breast milk significantly sooner than HIV-infected mothers (median 4.0 vs. 6.0 months, P=0.005). Infants born to HIV-negative mothers were weaned significantly later than HIV-exposed infants (median 19.0 vs. 6.0 months, P<0.0001). More than 90% of mothers reported that breast-feeding their infant was a personal decision, a third of whom also mentioned having taken into account health workers' messages. The authors conclude that the HIV-infected mothers interviewed were gradually implementing infant feeding practices recommended in the context of HIV. Increased infant feeding support capacity in resource-limited rural populations is required, i.e. training of counselling staff, decentralised follow-up and weaning support.

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Nutrition

Taha TE, Kumwenda NI, et al. The impact of breastfeeding on the health of HIV-positive mothers and their children in sub-Saharan Africa. Bull World Health Organ 2006;84:546-54.

Taha and colleagues assessed the impact of breastfeeding by women infected with HIV-1 on their morbidity and risk of mortality and on the mortality of their children. They analysed longitudinal data from two previous randomized clinical trials of mother-to-child transmission of HIV conducted between April 2000 and March 2003 in the Republic of Malawi, Africa. Mothers infected with HIV, and their newborns, were enrolled at the time of their child's birth; they then returned for follow-up visits when the child was aged 1 week, 6-8 weeks and then 3, 6, 9, 15, 18, 21 and 24 months. Patterns of breastfeeding (classified as exclusive, mixed or no breastfeeding), maternal morbidity and mortality, and mortality among their children were assessed at each visit. Descriptive and multivariate analyses were performed to determine the association between breastfeeding and maternal and infant outcomes. A total of 2000 women infected with HIV were enrolled in the original studies. During the 2 years after birth, 44 (2.2%) mothers and 310 (15.5%) children died; excluding multiple births. The median duration of breastfeeding was 18 months, exclusive breastfeeding 2 months and mixed feeding 12 month. Breastfeeding patterns were not significantly associated with maternal mortality or morbidity after adjusting for maternal viral load and other covariates. Breastfeeding was associated with reduced mortality among infants and children: overall breastfeeding (HR 0.44, 95%CI 0.28-0.70), mixed feeding (HR 0.45, 95%CI 0.28-0.71), and exclusive breastfeeding (HR 0.40, 95%CI 0.22-0.72). These protective effects were seen both in infants who were infected with HIV and those who were not. The authors conclude that breastfeeding by women infected with HIV was not associated with maternal mortality or morbidity; it was associated with highly significant reductions in mortality among their children.

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Reproductive Health and HIV

Silva NE, Alvarenga AT, Ayres JR. AIDS and pregnancy: meanings of risk and challenges for care. Rev Saude Publica. 2006;40:474-81. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0034-89102006000300016&lng=en&nrm=iso

Silva and colleagues conducted this qualitative study to understand how the risk of mother-to-child transmission of HIV is perceived and interpreted by people living with HIV, when making decisions regarding reproductive health. It was carried out at three municipal health clinics specializing in STD/AIDS, in the city of Sao Paulo, Brazil. Semi-structured thematic interviews were conducted with eight patients (male and female), from July to December 2001. The interviewees were key informants and either they or their partners were HIV positive. All of them were aged 18 or over and had been living with their partners for at least one year. The authors found that among the motivations for having children, those related to the partner's expectations were highlighted, especially as a form of compensation for their actions. Risk of transmission was used by health professionals both for discouraging pregnancy and for giving guidance on prophylaxis. However, reproductive issues were not voiced at the health clinics, either by the patients or by the healthcare providers. Silva and colleagues conclude that attention should be directed not only towards controlling the infection, but also most importantly towards the wellbeing of people living with HIV. They go further to say that there is a need to clarify the different points of view of users and professionals in order to achieve the most effective and appropriate solution for each specific care-giving situation.

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Mother- to- Child Transmission

European Collaborative Study. The mother-to-child HIV transmission epidemic in Europe: evolving in the East and established in the West. AIDS 2006;20:1419-27.http://gateway.ut.ovid.com/gw2/ovidweb.cgi

Photo credit: BOEHRINGER INGELHEIM
Photo credit: BOEHRINGER INGELHEIM
The European Collaborative Study (ECS) investigators carried out an epidemiological analysis of the emerging epidemic in the Ukraine and compared its approach to prevention of mother-to-child transmission (MTCT) with that in Western Europe. The ECS is a prospective cohort study established in 1985 in Western Europe and extended to Ukraine in 2000. The authors analysed data on 5967 HIV-infected pregnant women and their infants (1251 from Ukraine and 4716 from Western/Central Europe) and used logistic regression to identify factors associated with transmission. They found that HIV-infection among pregnant women enrolled in Western European centres has shifted from being largely injecting drug use (IDU)-related to heterosexually-acquired; in Ukraine IDU also gradually declined with women increasingly identified without specific risk factors. In Ukraine in 2000–2004 most women (80%) received single dose nevirapine and/or short-course zidovudine prophylaxis (with MTCT rate of 4.2%, 95%CI 1.8–8.0); 2% received antenatal HAART and 33% delivered by elective Caesarean section; in Western European centres 72% of women received HAART (MTCT rate 1.0%, 95% CI 0.4–1.9) and 66% delivered by elective Caesarean section during the same period. The authors conclude that their findings indicate distinct differences in the epidemics in pregnant women across Europe. The evolution of the MTCT epidemic in Ukraine does not appear to be following the same pattern as that in Western Europe in the 1980s and 1990s. Although uptake of preventive MTCT prophylaxis has been rapid in both Western Europe and Ukraine, substantial challenges remain in the more resource-constrained setting in Eastern Europe.

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Mother- to- Child Transmission

Centers for Disease Control and Prevention. Achievements in public health. Reduction in perinatal transmission of HIV infection--United States, 1985-2005. Morb Mortal Wkly Rep 2006;55:592-7.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5521a3.htm

During 2005, an estimated 92% of AIDS cases reported among children aged less than 13 years in the US were attributed to mother-to-child transmission of HIV. Transmission can occur during pregnancy, labour, delivery, or breastfeeding. Estimates of the number of perinatal HIV infections peaked in 1991 at 1,650 and declined to an estimated range of 144-236 in 2002. This reduction is attributed to universal HIV testing of pregnant women, use of antiretroviral drugs for treatment and prophylaxis, avoidance of breastfeeding, and use of elective Caesarean delivery when appropriate. With these interventions, rates of HIV transmission during pregnancy, labour, or delivery from mothers infected with HIV have been reduced to less than 2%, compared with transmission rates of 25%-30% with no intervention.

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