Mother-to-child Transmission Of HIV Research Articles

British HIV Association guidelines for the management ofHIVinfection in pregnant women 2012

British HIV Association guidelines for the management of<scp>HIV</scp>infection in pregnant women 2012

Naturally-Occurring Genetic Variants in Human DC-SIGN Increase HIV-1 Capture, Cell-Transfer and Risk of Mother-To-Child Transmission

BackgroundMother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cell–specific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages.Methods and FindingsWe have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1. DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection. Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163+ macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants. The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro.ConclusionThis study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.

HIV-1 Control in Battlegrounds: Important Host Genetic Variations for HIV-1 Mother-To-Child Transmission and Progression to Clinical Pediatric AIDS

HIV-1 mother-to-child transmission (MTCT) is the passing of maternal HIV-1 to the offspring during pregnancy, labor and delivery, and/or breastfeeding. HIV-1 MTCT and the evolution to pediatric AIDS are multifactorial, dynamic and variable phenotypic conditions. Both genetic and nongenetic variables can influence susceptibility to HIV-1 MTCT or the rate of progression to clinical pediatric AIDS. In this review, we summarize the current state of knowledge about the roles of genetic variations seen in host immune response genes, and those that have been independently associated, mostly through population genetics of candidate genes, with interindividual susceptibility to HIV-1 MTCT, and progression to pediatric AIDS. We examine common and rare host genetic variations at coding and noncoding polymorphisms, whether functional or not, in agonists and antagonists of the immune response, which have been implicated in HIV-1 control in battlegrounds of cell entry, replication and evolution to AIDS. Further, we point to over 380 single-nucleotide polymorphisms, mostly within the HLA super region, recently identified in unbiased genome-wide association studies of HIV replication and evolution in adults, still unexplored in the context of HIV-1 MTCT, and which are likely to also influence susceptibility to pediatric HIV-1/AIDS.

Altered Vaginal Microbiota Are Associated With Perinatal Mother-to-Child Transmission of HIV in African Women From Burkina Faso

Mother-to-child transmission (MTCT) of HIV remains a significant problem in resource-limited settings, despite the advent of antiretroviral therapies. Because perturbations in vaginal microbial communities are associated with sexual transmission of HIV, we determined whether perinatal MTCT is associated with the vaginal microbiotas of HIV-infected mothers. We conducted a retrospective analysis of cervicovaginal microbiotas by pyrosequencing of bacterial 16S rRNA genes (median 350 sequences per sample) from 10 transmitters and 54 nontransmitters during a perinatal MTCT prevention clinical trial of azidothymidine and the microbicide benzalkonium chloride. Logistic regression was performed adjusting for multiple covariates, including CD4(+) T-cell numbers and treatment group, to correlate abundances of microbial taxa with perinatal MTCT. The vaginal microbiotas of these subjects were dominated by several lactobacilli species, although a subset of subjects was colonized by diverse anaerobic species. MTCT of HIV was associated with significantly greater relative abundances of several groups of microorganisms. Most notably, among the abundant bacterial species, Gardnerella vaginalis was significantly enriched in cases of antepartum transmission, compared with nontransmission (odds ratio 1.7; P = 0.004). Neither azidothymidine nor benzalkonium chloride treatment was associated with shifts in microbial distributions compared with the placebo control group. These data suggest that alterations in vaginal microbial communities are associated with an increased risk for perinatal MTCT, consistent with results with horizontal transmission of HIV. Therefore, determining the mucosal features associated with alterations in vaginal microbial communities may guide efforts to modulate the risk for HIV MTCT.

Effectiveness of a Prevention of Mother-to-Child HIV Transmission Programme in an Urban Hospital in Angola

BackgroundAntiretroviral therapy is effective in reducing rates of mother-to child transmission of HIV to low levels in resource-limited contexts but the applicability and efficacy of these programs in the field are scarcely known. In order to explore such issues, we performed a descriptive study on retrospective data from hospital records of HIV-infected pregnant women who accessed in 2007–2010 the Luanda Municipal Hospital service for prevention of mother-to-child transmission (PMTCT). The main outcome measure was infant survival and HIV transmission. Our aim was to evaluate PMTCT programme in a local hospital setting in Africa.ResultsData for 104 pregnancies and 107 infants were analysed. Sixty-eight women (65.4%) had a first visit before or during pregnancy and received combination antiretroviral treatment (ART) in pregnancy. The remaining 36 women (34.6%) presented after delivery and received no ART during pregnancy. Across a median cohort follow-up time of 73 weeks, mortality among women with and without ART in pregnancy was 4.4% and 16.7%, respectively (death hazard ratio: 0.30, 95% CI 0.07–1.20, p = 0.089). The estimated rates of HIV transmission or death in the infants over a median follow up time of 74 weeks were 8.5% with maternal ART during pregnancy and 38.9% without maternal ART during pregnancy. Following adjustment for use of oral zidovudine in the newborn and exposure to maternal milk, no ART in pregnancy remained associated with a 5-fold higher infant risk of HIV transmission or death (adjusted odds ratio: 5.13, 95% CI: 1.31–20.15, p = 0.019).ConclusionsAmong the women and infants adhering to the PMTCT programme, HIV transmission and mortality were low. However, many women presented too late for PMTCT, and about 20% of infants did not complete follow up. This suggests the need of targeted interventions that maintain the access of mothers and infants to prevention and care services for HIV.

Prevention of Mother-to-Child HIV Transmission in Low-income Settings: Current Situation and Future Challenges

In the developing countries an estimated 2.5 million children under the age of 15 were living with HIV in 2009 and there were some 370 000 new HIV paediatric infections. Nearly all of these new infections could have been avoided with effective prevention of mother-to-child transmission (PMTCT) interventions. Any intervention dispensed with mother-to-child transmission (MTCT) rates range from 15-30% without breastfeeding to 30-45% with prolonged breastfeeding. In developing countries where elective caesarean section and breastfeeding avoidance are generally unsafe or unaccepted options antiretroviral drugs (ARVs) have been documented to reduce MTCT to 2% or below. Even though substantial achievements were recently reported in PMTCT in implementing Sub-Saharan Africa high-burden countries much more has quickly to be done to virtually eliminate MTCT of HIV by 2015. To this aim plenty of commitment and coordinated action by all involved parties including the private sector are needed. The challenges and critical points bound-up with the desired PMTCT outcomes are discussed in this review in the light of 2010 revised WHO recommendations for PMTCT in low-income HIV settings. They recommend HIV-infected pregnant women to start ARV therapy for their own health at CD4 cell count < 350/mm 3. Additionally they promote the use of ARVs for prophylaxis earlier in pregnancy beginning at 14 weeks and continuing through the end of breastfeeding period. Moreover in countries where breastfeeding is judged to be the best option HIV-infected mothers (whose infants are uninfected or unknown status) are recommended to continue breastfeeding for the first 12 months of life provided they are taking ARVs during that period.

Elevated cytokine and chemokine levels in the placenta are associated with in-utero HIV-1 mother-to-child transmission

To determine whether there is an association between cytokine and chemokine levels in plasma isolated from the placenta and HIV-1 mother-to-child transmission (MTCT). We designed a case-control study of HIV-infected, pregnant women enrolled in the Malaria and HIV in Pregnancy cohort. Participants were recruited in Blantyre, Malawi, from 2000 to 2004. Patients were women whose children were HIV-1 DNA-positive at birth (in-utero MTCT) or HIV-1 DNA-negative at birth and HIV-1 DNA-positive at 6 weeks postpartum (intrapartum MTCT); controls were women whose children were HIV-1 DNA-negative both at birth and 6 weeks postpartum. After delivery, blood was isolated from an incision on the basal plate of the placenta. We used a Bio-Plex human cytokine assay (Bio-Rad, Hercules, California USA) to simultaneously quantify 27 cytokines, chemokines and growth factors in placental plasma. HIV-1 RNA copies were quantified with the Roche Amplicor kit. Levels of interleukin (IL) 4, IL-5, IL-6, IL-7, IL-9, eotaxin, IL-1Ra and interferon gamma-induced protein 10 (IP-10) were significantly elevated in placental plasma isolated from cases of in-utero HIV-1 MTCT. In contrast, only granulocyte colony-stimulating factor was elevated in placental plasma isolated from cases of intrapartum MTCT. After adjusting for maternal age, gestational age and peripheral CD4(+) T-cell count, every log(10) increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT. Elevated cytokine and chemokine levels in placental plasma were associated with in-utero and not intrapartum MTCT. IP-10, which is both a T-cell chemokine and potentiator of HIV-replication, was robustly and independently associated with prevalent, in-utero MTCT.

Reducing mother-to-child transmission of HIV: findings from an early infant diagnosis program in south-south region of Nigeria

BackgroundEarly diagnosis of HIV in infants provides a critical opportunity to strengthen follow-up of HIV-exposed children and assure early access to antiretroviral (ARV) treatment for infected children. This study describes findings from an Early Infant Diagnosis (EID) program and the effectiveness of a prevention of mother-to-child transmission (PMTCT) intervention in six health facilities in Cross-River and Akwa-Ibom states, south-south Nigeria.MethodsThis was a retrospective study. Records of 702 perinatally exposed babies aged six weeks to 18 months who had a DNA PCR test between November 2007 and July 2009 were reviewed. Details of the ARV regimen received to prevent mother-to-child transmission (MTCT), breastfeeding choices, HIV test results, turn around time (TAT) for results and post test ART enrolment status of the babies were analysed.ResultsTwo-thirds of mother-baby pairs received ARVs and 560 (80%) babies had ever been breastfed. Transmission rates for mother-baby pairs who received ARVs for PMTCT was 4.8% (CI 1.3, 8.3) at zero to six weeks of age compared to 19.5% (CI 3.0, 35.5) when neither baby nor mother received an intervention. Regardless of intervention, the transmission rates for babies aged six weeks to six months who had mixed feeding was 25.6% (CI 29.5, 47.1) whereas the transmission rates for those who were exclusively breastfed was 11.8% (CI 5.4, 18.1). Vertical transmission of HIV was eight times (AOR 7.8, CI: 4.52-13.19) more likely in the sub-group of mother-baby pairs who did not receive ARVS compared with mother-baby pairs that did receive ARVs. The median TAT for test results was 47 days (IQR: 35-58). A follow-up of 125 HIV positive babies found that 31 (25%) were enrolled into a paediatric ART program, nine (7%) were known to have died before the return of their DNA PCR results, and 85 (67%) could not be traced and were presumed to be lost-to-follow-up.ConclusionReduction of MTCT of HIV is possible with effective PMTCT interventions, including improved access to ARVs for PMTCT and appropriate infant feeding practices. Loss to follow up of HIV exposed infants is a challenge and requires strategies to enhance retention.

What will it take to eliminate pediatric HIV? Reaching WHO target rates of mother-to-child HIV transmission in Zimbabwe: a model-based analysis.

The World Health Organization (WHO) has called for the "virtual elimination" of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe. We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/µl; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines' "Option A" (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO "Option B" (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning. The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%-7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%. Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the "virtual elimination" of pediatric HIV in Zimbabwe. Please see later in the article for the Editors' Summary.

Preventing Mother-To-Child Transmission of HIV within HIV Proposals Funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria

Objectives: To analyse interventions for the prevention of mother-to-child-transmission of HIV (PMTCT) included in HIV proposals approved for funding by the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund) Methods: The global strategy for PMTCT outlines four main components. Individual approved HIV proposals submitted to the Global Fund were analysed for these componen Results: In total, 345 original HIV proposals approved for funding from Rounds 1 to 9 were reviewed. The four components of the global PMTCT strategy do not feature equally. In particular, prevention of unintended pregnancies in HIV infected women (component 2) was the least represented, appearing in 34% of the proposals. On the other hand, preventing HIV transmission from a woman living with HIV to her infant (component 3) was present in approximately 90%. However, component 2 represents the only component that consistently increased throughout the Rounds, with signs of the greatest increase between Rounds 3 and Conclusions: The global community has committed itself to accelerate progress towards the prevention of mother- to-child HIV transmission (MTCT) by 2015 through the initiative to eliminate new paediatric HIV infections. Given this commitment, it is important for countries to support comprehensive PMTCT interventions that are balanced across the four components. The Global Fund is one of the largest donors and this study shows interventions that countries could capitalize on to scale-up PMTCT efforts as well as synergize efforts in linking with other global and national initiatives in maternal, reproductive, and child health.

Prevention of Mother-to-Child HIV-1 Transmission—Why We Still Need a Preventive HIV Immunization Strategy

There has been dramatic progress in identification of effective interventions to prevent mother-to-child HIV-1 transmission (PMTCT) in low-resource countries and rapid scaleup to implement these interventions in the last 5 years. The proportion of pregnant women tested for HIV-1 in low-resource countries has increased from 7% in 2005 to 26% in 2009, and the proportion of HIV-1–infected pregnant women receiving antiretroviral prophylaxis has increased from 15% in 2005 to 53% in 2009. A 24% reduction in estimated annual new infant HIV-1 infections was observed between 2005 and 2009 in the 25 low-resource countries, where approximately 91% of HIV-1–infected pregnant women reside. Joint United Nations Program on HIV/AIDS (UNAIDS) has developed a plan for global virtual elimination of mother-to-child HIV-1 transmission (MTCT), with a goal to reduce the number of new infant HIV-1 infections by 90% and MTCT to ,5% between 2009 and 2015. However, we remain far short of the goal of global MTCT elimination. In 2009, there remained an estimated 347,000 new infant infections in the 25 countries discussed above, with 40%–50% of these infections acquired through breastfeeding. Optimal prevention requires identification of maternal HIV-1 infection early in pregnancy with prompt initiation of antiretroviral drugs for treatment or prophylaxis, yet many women in lowresource countries access prenatal care late, only at delivery or do not deliver in medical settings. Provision of the infant PMTCT antiretroviral prophylaxis component remains low, with coverage increasing only slightly from 32% in 2008 to 35% in 2009. Although current World Health Organization guidelines now recommend breastfeeding for 12 months with concurrent infant or maternal antiretroviral prophylaxis, new reports suggest weaning before age 18 months is associated with elevated morbidity and mortality and that reduced risk of diarrhea-related morbidity and mortality among HIV-1–exposed uninfected children is associated with continuing breastfeeding after age 12 months even when replacement and complementary foods and counseling are provided. Thus, interventions to allow safe breastfeeding longer than 12 months are important to optimize infant survival. Finally, HIV-1 seroconversion rates of 3%–10% in uninfected pregnant or lactating women have been reported in HIV-1 endemic settings, which are associated with high risk of MTCT; it is estimated that 40% of new infant infections in Botswana are due to acute maternal infection during pregnancy or lactation. Although antiretroviral prophylaxis significantly reduces MTCT, effective implementation is complicated by need for prolonged drug administration and adherence, potential toxicities leading to continued monitoring requirements, potential for drug resistance, and inadequate health-care infrastructure. Additionally, even with maternal triple-drug prophylaxis, most studies demonstrate cumulative residual MTCT rates of 2%–5% at age 6 months. Thus, continued investigation of preventive immunologic interventions including maternal and/or infant passive/active immunization to reduce MTCT remains important. Although antiretroviral prophylaxis is the foundation for PMTCT, immunization strategies could provide a safe and durable adjunctive intervention to prevent transmission, particularly during breastfeeding. Immunization strategies, if found to be efficacious, have the advantage of being less reliant on patient adherence and health-care infrastructure than are drug interventions.

Preventing HIV in U.S. Women and Girls: A Call for Social Action

Successes in HIV prevention efforts in the U.S. have resulted in drastic reductions in the number of new infections in the U.S. among white gay men and injection drug users, a stabilization in overall annual rates of new HIV infections, and near eradication of mother-to child transmission of HIV. Despite this remarkable progress, the proportion of AIDS cases in women has slowly, quietly, and steadily increased from 7% in 1985 to 25% in 2008. The fact the prevention efforts have not reduced HIV spread among women suggests that targeting the individual behaviors of women to prevent HIV acquisition is not a sufficiently effective public health strategy. Interventions that more broadly address the needs of women and their families, and address the contextual factors in which HIV risk occurs are more likely to lead to measurable and sustainable progress. Over the past 30 years, we have seen the U.S. HIV epidemic in women become similar to patterns of HIV risk among women in the developing world. In 2009, 85% of women who acquired HIV became infected through sex with a man and the majority (83%) of them were non-white women. Efforts to understand these immense disparities and create gender-responsive strategies must be a priority within our National HIV/AIDS Strategy.

Perception of Risk of Vertically Acquired HIV Infection and Acceptability of Provider-Initiated Testing and Counseling Among Adolescents in Zimbabwe

We investigated attitudes toward provider-initiated HIV testing and counseling (PITC) in the suburbs of Harare, Zimbabwe, where late presentation after mother-to-child HIV transmission (MTCT) is a major cause of adolescent mortality. Adolescents (10-18 years) attending 2 primary clinics were offered PITC. Participants completed a questionnaire investigating acceptability of PITC, and in-depth interviews with 41 adolescents and 30 guardians explored understanding of long-term survival after MTCT. Of 506 participants, 16 were known to be HIV-positive; of the remaining 490, only 5 (1%) declined HIV testing. Infected adolescents and their guardians often anticipated a positive result and reported being advised by relatives (but not health workers) to be tested because of chronic illness, especially if parents or siblings had died or were HIV-infected. However, HIV-negative participants were not aware that long-term survival following MTCT could occur. All adolescents felt that HIV diagnosed at their age would be assumed to have been sexually acquired regardless of the true mode of transmission. Including late diagnosis of MTCT in pretest counseling and health educational messages may facilitate PITC for older children and adolescents, especially for those who have not had their sexual debut.

Barriers to Prevention of HIV Type 1 Mother-to-Child-Transmission in Bahia, Brazil

Editor: In Brazil, the AIDS epidemic has recently spread to small towns and the peripheral areas of large cities, involving mostly people younger than 21 or older than 50 years.1 In addition, the number of infected women (through the sexual route) is also increasing, mostly in the poorest areas of the country (the North and Northeast regions), but also in some well-developed areas, such as the South region.1 Brazil provides universal access to antiretroviral drugs, as well as to viral load, CD4+ cell count, and resistance tests. However, most of the patients are still being diagnosed late in the course of the disease, which increases hospitalization rates and morbidity/mortality.1 This is especially important for pregnant women, since a delay in diagnosis may increase the likelihood of mother-to-child transmission (MTCT).2 In Brazil, around 3 million deliveries occur every year. Since the estimated prevalence rate of HIV-1 infection in pregnant women is 0.42%, we should expect at least 12,000 new cases of HIV infection per year in this specific population. However, only 4980 cases were reported in 2008, 125 of them in Bahia, a Northeast state of Brazil.3 This suggests that only half of the cases are diagnosed and/or reported. The incidence rate of HIV infection for children younger than 5 years is 3.0 cases per 100,000 inhabitants, in Bahia (over 90% due to MTCT).1,3 As part of a study conducted to identify the prevalence and risk factors for acquiring HIV-1 infection, we interviewed 3300 parturient women who attended the main public maternity hospital of Bahia state from May 2008 to April 2009.4 The maternity hospital is used by about 40% of all parturient women in Salvador and the surrounding area, and is the referral hospital for complex cases, which includes parturient women with AIDS. As part of the routine care, all parturient women are tested for HIV-1 (two different rapid tests) when they are admitted to the maternity unit. Positive samples are retested by enzyme immunoassay. We found an HIV-1 seroprevalence rate of 0.84% (28/3300, 95% CI: 0.57–1.24). Of note, 8 out of 28 (28.6%) women were already diagnosed as HIV positive before pregnancy and were receiving regular care in a public HIV referral center. The remaining 20 (71.4%) were diagnosed during pregnancy: 10/28 (35.7%) during prenatal care, 9/28 (32.1%) by rapid testing during admission for labor and delivery, and 1/28 (3.5%) immediately after delivery. Ten (35.7%) cases of HIV infection were detected only on admission to the maternity hospital. Of concern, among those with a late diagnosis, only one (10%) received proper HIV-1 prophylaxis during labor. As a referral hospital for complex cases, antiretroviral drugs are readily available, and the staff was previously trained, as part of a national program for the prevention of HIV-1 MTCT. Moreover, after discharge from the hospital, 7/28 (25%) of the diagnosed women (and their newborns) were lost to follow-up. They never returned for scheduled medical visits, the home addresses and telephone numbers they provided when admitted to the hospital were not valid, and they could not be traced. As far as we could determine, they had not been reported to the Public Health authorities, and no effort to locate them was done by hospital/health authorities. All 21 newborns tested for HIV-1 by b-DNA, and proviral DNA, were negative at 4 and 12 weeks of age. Among the seven lost mother–newborn pairs, six mothers (86%) were diagnosed only upon hospital admission. These data reveal that regardless of the great effort made by Brazilian health authorities to control the AIDS epidemic, several problems are still occurring, and many opportunities are lost. Our report clearly identifies some serious failures in the process: most of the parturient women were diagnosed only at the hospital, and even among those already known to be HIV positive, antiretroviral drugs were prescribed in only 72% of the cases. Most importantly, barely 10% of late-diagnosed women received any type of prophylaxis for MTCT, and 86% of them were lost to follow-up, resulting in a likely increase in the chance of MTCT through breastfeeding, as well as the probability of transmission to their sexual partners. Better surveillance of HIV-1 infections in pregnancy and careful follow-up of positive mothers and their infants are mandatory.

P5-S6.01 Towards universal access to prevention mother to child HIV-transmission (PMTCT) services leading to elimination of mother to child HIV-transmission (MTCT) in Rwanda

BackgroundPMTCT related activities in Rwanda began in 1999 with a piloting phase in Kicukiro Health Centre in Kigali City. Subsequently, PMTCT service delivery has been expanded and over 74% of...

Nonbreast-Fed HIV-1-Exposed Burkinabe Infants Have Low Energy Intake between 6 and 11 Months of Age Despite Free Access to Infant Food Aid1–3

In a WHO-coordinated, mother-to-child HIV transmission (MTCT) prevention trial in Burkina Faso, HIV-1–infected mothers were advised to either stop breast-feeding by 6 mo or totally avoid it. Participants were provided with cereal-based, infant fortified mix (IFM) from 6 to 12 mo postpartum along with infant feeding counseling. Our objective was to describe nonbreast-fed infants' food consumption and adequacy of nutrient intake. A 1-d weighed food record and one 24-h dietary recall were performed in 68 nonbreast-fed, non-HIV–infected 6- to 11-mo-old infants. Mean food energy density and feeding frequency were satisfactory in 6–8 mo olds [0.8 ± 0.2 kcal/g (3.3 ± 0.9 kJ/g) and 7.2 ± 1.6 times/d] and in 9–11 mo olds [0.9 ± 0.2 kcal/g (3.6 ± 0.8 kJ/g) and 7.7 ± 2.1 times/d]. Median energy intake was 523 kcal [range: 82–1053 (2187 kJ, range: 345–4401)] in 6–8- and 811 kcal [range: 34–1543 (3392 kJ, range: 144–6452)] in 9–11-mo-old infants, respectively. Approximately 75% of their energy intake was provided by subsidized foods (milk that mothers obtained from support networks and IFM). One-half of the infants had intakes < 80 kcal/kg (<334 kJ/kg) on the day of the survey, mainly because IFM and milk were consumed in amounts that were too low. Thus, coverage of energy needs required a diet with sufficient amounts of both IFM and milk in these vulnerable infants. These findings argue for the development of adequate, sustainable infant fortified foods and their rapid integration into MTCT prevention services. They also lend support to the recent revision of WHO infant feeding guidance for future MTCT prevention programming that recommends breast-feeding up to 12 mo postpartum (under cover of antiretroviral prophylaxis) as the safest feeding option for infants of HIV-infected mothers.

Effectiveness of a PMTCT programme in rural Western Kenya

We assess the coverage of a Prevention of Mother-to-child Transmission (PMTCT) programme in Busia (Kenya) from 1 January 2006 to 31 December 2008 and estimate the risk of transmission of HIV. We also estimate the odds of HIV transmission according to pharmacological intervention received. Programme coverage was estimated as the proportion of mother–baby pairs receiving any antiretroviral (ARV) regimen among all HIV-positive women attending services. We estimated the mother-to-child transmission (MTCT) rate and their 95% confidence interval (95%CI) using the direct method of calculation (intermediate estimate). A case–control study was established among all children born to HIV-positive mothers with information on outcome (HIV status of the babies) and exposure (data on pharmacological intervention). Cases were all HIV-positive children and controls were the HIV-negative ones. Exposure was defined as: (1) complete protocol: ARV prescribed according World Health Organisation recommendations; (2) partial protocol: does not meet criteria for complete protocol; and (3) no intervention: ARVs were not prescribed to both mother and child. Babies were tested using DNA Polymerase Chain Reaction at six weeks of life and six weeks after breastfeeding ceased. In the study period, 22,566 women accepted testing, 1668 were HIV positive (7.4%; 95%CI 7.05–7.73); 1036 (62%) registered in the programme and 632 were lost. Programme coverage was 40.4% (95%CI 37.9–42.7). Out of the 767 newborns, 28 (3.6%) died, 148 (19.3%) defaulted, 282 (36.7%) were administratively censored and 309 (40.2%) babies completed the follow-up as per protocol; 49 were HIV positive and MTCT risk was 15.86% (95%CI 11.6–20.1). The odds of having an HIV-positive baby was 4.6 times higher among pairs receiving a partial protocol compared to those receiving a complete protocol and 43 times higher among those receiving no intervention. Our data show a good level of enrolment but low global coverage rate. It demonstrates that ARV regimens can be implemented in low resource rural settings with marked decreases of MTCT. Increasing the coverage of PMTCT programmes remains the main challenge.

HIV-1 co-receptor usage:influence on mother-to-child transmission and pediatric infection

Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers.The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5narrow and R5broad resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.

The cost-effectiveness of preventing mother-to-child transmission of HIV in low- and middle-income countries: systematic review

BackgroundAlthough highly effective prevention interventions exist, the epidemic of paediatric HIV continues to challenge control efforts in resource-limited settings. We reviewed the cost-effectiveness of interventions to prevent mother-to-child transmission (MTCT) of HIV in low- and middle-income countries (LMICs). This article presents syntheses of evidence on the costs, effects and cost-effectiveness of HIV MTCT strategies for LMICs from the published literature and evaluates their implications for policy and future research.MethodsCandidate studies were identified through a comprehensive database search including PubMed, Embase, Cochrane Library, and EconLit restricted by language (English or French), date (January 1st, 1994 to January 17th, 2011) and article type (original research). Articles reporting full economic evaluations of interventions to prevent or reduce HIV MTCT were eligible for inclusion. We searched article bibliographies to identify additional studies. Two authors independently assessed eligibility and extracted data from studies retained for review. Study quality was appraised using a modified BMJ checklist for economic evaluations. Data were synthesised in narrative form.ResultsWe identified 19 articles published in 9 journals from 1996 to 2010, 16 concerning sub-Saharan Africa. Collectively, the articles suggest that interventions to prevent paediatric infections are cost-effective in a variety of LMIC settings as measured against accepted international benchmarks. In concentrated epidemics where HIV prevalence in the general population is very low, MTCT strategies based on universal testing of pregnant women may not compare well against cost-effectiveness benchmarks, or may satisfy formal criteria for cost-effectiveness but offer a low relative value as compared to competing interventions to improve population health.Conclusions and RecommendationsInterventions to prevent HIV MTCT are compelling on economic grounds in many resource-limited settings and should remain at the forefront of global HIV prevention efforts. Future cost-effectiveness analyses can help to ensure that pMTCT interventions for LMICs reach their full potential by focussing on unanswered questions in four areas: local assessment of rapidly evolving HIV MTCT options; strategies to improve coverage and reach underserved populations; evaluation of a more comprehensive set of MTCT approaches including primary HIV prevention and reproductive counselling; integration of HIV MTCT and other sexual and reproductive health services.

Safety and Tolerability of Antiretrovirals during Pregnancy

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.