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Competing Interests: We declare no competing interests.

Background: Infant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother's viral load is <1,000 cp/mL. The PROMISE-EPI study, modified the PNP regimen to lamivudine only, initiated at 6 weeks and continued until 12 months to all HIV exposed uninfected infants of virally unsuppressed mothers. Our aim in this analysis was to identify barriers and facilitators to this extended PNP, the keystone toward an effective prevention., Methods: Individual interviews and focus group discussion (FGD) were conducted with PROMISE-EPI participants who had received prophylaxis for their children from the national program up to 6 weeks and then lamivudine oral solution in PROMISE-EPI study. Health care providers and PROMISE-EPI staff were also interviewed. Sessions were recorded, transcribed verbatim and translated from local languages into English. An initial code-book was designed and then adapted on the basis of the emerging themes, to allow a descriptive thematic analysis., Results: More barriers to PNP adherence were identified with triple drug prophylaxis than with lamivudine. These barriers were related to the formulation and bitter taste of AZT/3TC tablets. The ready to use formulation and sweet taste of lamivudine syrup were appreciated by mothers. Extended PNP proposed in the PROMISE-EPI study was globally well accepted and strategies were found to increase adherence. Adherence to lamivudine appeared to be better than the mothers' adherence to their own antiretroviral therapy., Conclusion: Accompanying mothers living with HIV and giving them the choice of the PNP to prevent transmission via breastfeeding (type of PNP regimen and extended PNP in non-adherent mothers), may be one of the keys to reducing the burden of pediatric HIV acquisition in low and middle income countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mennecier, Matoka, Wilfred-Tonga, Chunda-Liyoka, Mwiya, Nagot, Molès, Van de Perre, Kankasa and King.)

Objective: To evaluate the performance of the cascade of activities for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) at the second immunization visit in Burkina Faso., Methods: In a cross-sectional study, we recruited mothers attending the second immunization visit for their infant in 20 health centres of Bobo-Dioulasso city, Burkina Faso over 12 months (2019-2020). We administered a short questionnaire to 14 176 mothers and performed HIV serological tests on mothers who had not been tested in the last 3 months. All mothers were asked about their attendance for antenatal care and HIV rapid testing. HIV-infected mothers were also asked about the timing of their HIV diagnosis, antiretroviral therapy, pre-exposure prophylaxis initiation at birth and infant diagnosis of HIV., Findings: Of 14 136 respondents, 13 738 (97.2%) had at least one HIV serological test in their lifetime. Of 13 078 mothers who were never tested or were HIV-negative, 12 454 (95.2%) were tested during or after their last pregnancy. Among HIV-infected mothers already aware of their status, 110/111 (99.1%) women were on antiretroviral therapy. Among HIV-exposed infants, 84/101 (83.2%) babies received 6 weeks of antiretroviral prophylaxis at birth and 58/110 (52.7%) had a blood sample collected for early infant diagnosis. Only two mothers received their child's test results at the time of the second immunization visit. Four mothers were newly diagnosed as HIV-positive during the study., Conclusion: Collecting data at the second immunization visit, a visit rarely missed by mothers, could be useful for identifying gaps in the PMTCT cascade in settings where mothers are difficult to reach, such as in low-income countries with intermediate or low HIV prevalence., ((c) 2022 The authors; licensee World Health Organization.)

Competing Interests: Competing interests: All authors have read and understood BMJ policy on declaration of interests and have no interests to declare. The article was funded by the South African Medical Research Council. The content is the sole responsibility of the authors and does not necessarily represent the official views of the organisations and funders.

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In addition to providing life-giving nutrients and other substances to the breastfed infant, human milk can also represent a vehicle of pathogen transfer. As such, when an infectious disease outbreak, epidemic, or pandemic occurs-particularly when it is associated with a novel pathogen-the question will naturally arise as to whether the pathogen can be transmitted through breastfeeding. Until high-quality data are generated to answer this question, abandonment of breastfeeding due to uncertainty can result. The COVID-19 pandemic, which was in full swing at the time this document was written, is an excellent example of this scenario. During these times of uncertainty, it is critical for investigators conducting research to assess the possible transmission of pathogens through milk, whether by transfer through the mammary gland or contamination from respiratory droplets, skin, breast pumps, and milk containers, and/or close contact between mother and infant. To promote the most rigorous science, it is critical to outline optimal methods for milk collection, handling, storage, and analysis in these situations, and investigators should openly share their methods in published materials. Otherwise, the risks of inconsistent test results from preanalytical and analytical variation, false positives, and false negatives are unacceptably high and the ability to provide public health guidance poor. In this study, we provide "best practices" for collecting human milk samples for COVID-19 research with the intention that this will also be a useful guide for future pandemics.

Can the campaign Undetectable=Untransmittable (U=U), established for the sexual transmission of HIV, be applied to the transmission of HIV through breastfeeding? European AIDS Clinical Society and, to some extent, American guidelines now state that mothers with HIV who wish to breastfeed should be supported, with increased clinical and virological monitoring. This Viewpoint summarises existing evidence on transmission of HIV through breastfeeding, differences in HIV dynamics and viral load between breastmilk and plasma, and the effects of antiretroviral therapy on infants. At present, insufficient evidence exists to make clear recommendations for the required frequency of clinical and virological monitoring for mother and infant in a breastfeeding relationship or for the action to be taken in the event of viral rebound. We propose a roadmap for collaborative research to provide the missing evidence required to enable mothers who wish to breastfeed to make a fully informed choice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter), 5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3 mg/liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg · h/liter (IQR, 4.1 to 7.8 mg · h/liter), 5.9 mg · h/liter (IQR, 5.1 to 7.5 mg · h/liter), and 7.3 mg · h/liter (IQR, 4.9 to 8.5 mg · h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the therapeutic ones. For treatment, the WHO dosing guidelines should be suitable to maintain values above the therapeutic pharmacokinetic targets in most infants. (This study has been registered at ClinicalTrials.gov under identifier NCT00640263.)., (Copyright © 2017 American Society for Microbiology.)

Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding., Methods: We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263., Findings: Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group., Interpretation: Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding., Funding: INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Exposure of the infant's gut to cell-associated and cell-free HIV-1 trafficking in breast milk (BM) remains a primary cause of mother-to-child transmission (MTCT). The mammary gland represents a unique environment for HIV-1 replication and host-virus interplay. We aimed to explore the origin of the virus transmitted during breastfeeding, and the link with quasi-species found in acellular and cellular fractions of breast-milk (BM) and in maternal plasma. The C2-V5 region of the env gene was amplified, cloned and sequenced from the RNA and DNA of BM, the RNA from the mother's plasma (PLA) and the DNA from infant's dried blood spot (DBS) in 11 post-natal mother-infant pairs. Sequences were assembled in Geneious, aligned in ClustalX, manually edited in SeAL and phylogenetic reconstruction was undertaken in PhyML and MrBayes. We estimated the timing of transmission (ETT) and reconstructed the time for the most recent common ancestor (TMRCA) of the infant in BEAST. Transmission of single quasi-species was observed in 9 of 11 cases. Phylogenetic analysis illustrated a BM transmission event by cell-free virus in 4 cases, and by cell-associated virus in 2 cases but could not be identified in the remaining 5 cases. Molecular clock estimates, of the infant ETT and TMRCA, corresponded well with the timing of transmission estimated by sequential infant DNA PCR in 10 of 11 children. The TMRCA of BM variants were estimated to emerge during gestation in 8 cases. We hypothesize that in the remaining cases, the breast was seeded with a long-lived lineage latently infecting resting T-cells. Our analysis illustrated the role of DNA and RNA virus in MTCT. We postulate that DNA archived viruses stem from latently infected quiescent T-cells within breast tissue and MTCT can be expected to continue, albeit at low levels, should interventions not effectively target these cells.

Objective: To investigate the association between feeding patterns and HIV-free survival in children born to HIV-infected mothers and to clarify whether antiretroviral (ARV) prophylaxis modifies the association., Methods: From June 2005 to August 2008, HIV-infected pregnant women were counseled regarding infant feeding options, and randomly assigned to triple-ARV prophylaxis (triple ARV) until breastfeeding cessation (BFC) before age 6 months or antenatal zidovudine with single-dose nevirapine (short-course ARV). Eighteen-month HIV-free survival of infants HIV-negative at 2 weeks of age was assessed by feeding patterns (replacement feeding from birth, BFC <3 months, BFC ≥3 months)., Results: Of the 753 infants alive and HIV-negative at 2 weeks, 28 acquired infection and 47 died by 18 months. Overall HIV-free survival at 18 months was 0.91 [95% confidence interval (CI): 0.88-0.93]. In the short-course ARV arm, HIV-free survival (0.88; CI: 0.84-0.91) did not differ by feeding patterns. In the triple ARV arm, overall HIV-free survival was 0.93 (CI: 0.90-0.95) and BFC <3 months was associated with lower HIV-free survival than BFC ≥3 months (adjusted hazard ratio: 0.36; CI: 0.15-0.83) and replacement feeding (adjusted hazard ratio: 0.20; CI: 0.04-0.94). In the triple ARV arm, 4 of 9 transmissions occurred after reported BFC (and 5 of 19 in the short-course arm), indicating that some women continued breastfeeding after interruption of ARV prophylaxis., Conclusions: In resource-constrained settings, early weaning has previously been associated with higher infant mortality. We show that, even with maternal triple-ARV prophylaxis during breastfeeding, early weaning remains associated with lower HIV-free survival, driven in particular by increased mortality.

Objective: Postnatal HIV-1 mother-to-child transmission (MTCT) occurs in spite of antiretroviral therapy. Co-infections in breast milk with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are associated with increased HIV-1 shedding in this compartment. We investigated CMV levels and EBV detection in breast milk as potential risk factors for MTCT of HIV-1 via breastfeeding., Methods: Cell-free HIV-1 RNA, cell-associated HIV-1 DNA, CMV and EBV DNA were quantified in breast milk from 62 HIV-infected mothers and proven postnatal MTCT of HIV-1 via breastfeeding. Controls were 62 HIV-positive mothers with HIV-uninfected infants., Results: Median (interquartile range) CMV DNA viral load was significantly higher in cases [88,044 (18,586-233,904)] than in controls [11,167 (3221-31,152)] copies/10 breast milk cells (P < 0.001). Breast milk CMV DNA level correlated positively with breast milk HIV-1 RNA level in cases and controls. EBV DNA was detectable in a higher proportion of breast milk samples of cases (37.1%) than controls (16.1%; P = 0.009). HIV-1 MTCT was strongly associated with HIV-1 RNA shedding in breast milk and plasma. In multivariable analysis, every 1 log10 increase in breast milk CMV DNA was associated with a significant 2.5-fold greater odds of MTCT of HIV-1, independent of breast milk and plasma HIV-1 levels; the nearly three-fold increased risk of HIV-1 MTCT with breast milk EBV DNA detection did not reach significance., Conclusion: We provide the first evidence of an independent association between CMV in breast milk, and postnatal MTCT of HIV-1. This association could fuel persistent shedding of HIV-1 in breast milk in women receiving antiretroviral therapy. EBV DNA detection in breast milk may also be associated with MTCT of HIV-1, but only marginally so.

There is increasing evidence to support a relationship between human immunodeficiency virus (HIV-1) transmission through breastfeeding and milk host factors. We analyzed skim milk proteome to further determine the contribution of host factors to the risk of mother-to-child transmission of HIV-1. Quantitative mass spectrometry analysis was performed on nine case-control pairs of HIV+ transmitter/nontransmitter mothers, and specific biochemical assays on two selected proteins were assessed in an independent validation set of 127 samples. 33 identified proteins were differentially expressed between HIV+ transmitter and nontransmitter mothers. Among them, β2-microglobulin was significantly higher in the maternal transmitter than in the nontransmitter groups (p value = 0.0007), and S100A9 was significantly higher in the early maternal transmitter cases (before 4 months of age) compared with the nontransmitters (p value = 0.004). β2-Microglobulin correlated with milk and plasma HIV viral load and CD4+ cell count, whereas S100A9 correlated with the estimated timing of infection of the infant through breastfeeding. Finally, β2-microglobulin concentration in milk could accurately predict the risk of HIV-1 postnatal transmission by breastfeeding (p value < 0.0001, log-rank test). In conclusion, milk β2-microglobulin and S100A9 are host factors that are found to be associated with mother-to-child transmission of HIV-1.

Background: Postnatal transmission of HIV-1 through breast milk remains an unsolved challenge in many resource-poor settings where replacement feeding is not a safe alternative. WHO now recommends breastfeeding of infants born to HIV-infected mothers until 12 months of age, with either maternal highly active antiretroviral therapy (HAART) or peri-exposure prophylaxis (PEP) in infants using nevirapine. As PEP, lamivudine showed a similar efficacy and safety as nevirapine, but with an expected lower rate of resistant HIV strains emerging in infants who fail PEP, and lower restrictions for future HIV treatment. Lopinavir/ritonavir (LPV/r) is an attractive PEP candidate with presumably higher efficacy against HIV than nevirapine or lamivudine, and a higher genetic barrier to resistance selection. It showed an acceptable safety profile for the treatment of very young HIV-infected infants. The ANRS 12174 study aims to compare the risk of HIV-1 transmission during and safety of prolonged infant PEP with LPV/r (40/10 mg twice daily if 2-4 kg and 80/20 mg twice daily if >4 kg) versus Lamivudine (7,5 mg twice daily if 2-4 kg, 25 mg twice daily if 4-8 kg and 50 mg twice daily if >8 kg) from day 7 until one week after cessation of BF (maximum 50 weeks of prophylaxis) to prevent postnatal HIV-1 acquisition between 7 days and 50 weeks of age., Methods: The ANRS 12174 study is a multinational, randomised controlled clinical trial conducted on 1,500 mother-infant pairs in Burkina Faso, South Africa, Uganda and Zambia. We will recommend exclusive breastfeeding (EBF) until 26th week of life and cessation of breastfeeding at a maximum of 49 weeks in both trial arms.HIV-uninfected infants at day 7 (± 2 days) born to HIV-1 infected mothers not eligible for HAART who choose to breastfeed their infants.The primary endpoint is the acquisition of HIV-1 (as assessed by HIV-1 DNA PCR) between day 7 and 50 weeks of age. Secondary endpoints are safety (including resistance, adverse events and growth) until 50 weeks and HIV-1-free survival until 50 weeks., Discussion: This study will provide a new evidence-based intervention to support HIV-1-infected women not eligible for HAART to safely breastfeed their babies.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Introduction: Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum., Materials and Methods: Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission., Results: There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33-4.59) vs. aHR 1.52 (95% CI, 1.17-1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64-3.92) vs. 1.73 (95% CI 0.94-3.19), respectively]., Conclusions: The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.

Background: We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure., Methods: Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern., Results: Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ~15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 10⁶ copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001)., Conclusions: Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants.

Objectives: To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery., Design: Prospective cohort study., Setting: Urban Zimbabwe., Participants: 14 110 women and infants enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001)., Main Outcome Measures: Mother to child transmission of HIV, and breast milk and maternal plasma HIV load during the postpartum period., Results: Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log(10) copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log(10) copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log(10) copies/mL 0-30 days after infection, but rapidly declined to 2.0 log(10) copies/mL and <1.5 log(10) copies/mL by 31-90 days and more than 90 days, respectively. Among women whose plasma sample collected soon after delivery tested negative for HIV with ELISA but positive with PCR (n=17), 75% of their infants were infected or had died by 12 months. An estimated 18.6% to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO trial occurred among mothers who seroconverted postnatally., Conclusions: Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the "window period" of an antibody based test, when she would test HIV negative using one of these tests. Trial registration Clinical trials.gov NCT00198718.

Breast-feeding substantially increases the risk of HIV-1 transmission from mother to child, and although peripartum antiretroviral therapy prophylaxis significantly decreases the risk of mother-to-child transmission around the time of delivery, this approach does not affect breast-feeding transmission. Increased maternal RNA viral load in plasma and breast milk is strongly associated with increased risk of transmission through breast-feeding, as is breast health, and it has been suggested that exclusive breast-feeding could be associated with lower rates of breast-feeding transmission than mixed feeding of both breast- and other milk or feeds. Transmission through breast-feeding can take place at any point during lactation, and the cumulative probability of acquisition of infection increases with duration of breast-feeding. HIV-1 has been detected in breast milk in cell-free and cellular compartments; infant gut mucosal surfaces are the most likely site at which transmission occurs. Innate and acquired immune factors may act most effectively in combination to prevent primary HIV-1 infection by breast milk.

Objectives: To study mother to child HIV-1 transmission (MTCT) and infant mortality following benzalkonium chloride (BC) disinfection., Methods: A randomised, double blind phase II placebo controlled trial. Women testing positive for HIV-1 infection in prenatal care units in Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso, from November 1996 to April 1997 were eligible, with their informed consent. Women self administered daily a vaginal suppository of 1% BC (53) or matched placebo (54) from 36 weeks of pregnancy, plus a single dose during labour. The neonate was bathed with 1% BC solution or placebo within 30 minutes after birth. MTCT rate was assessed based on repeated polymerase chain reaction (PCR) and serology results. For the present analysis, children were followed up to 15 months., Results: A total of 107 women were enrolled. Of 103 eligible liveborn children, 23 were HIV infected, 75 uninfected, and five of indeterminate status. MTCT transmission rate was 24.2% overall (95% confidence interval (CI): 14.3% to 30.4%). On an intent to treat basis, the transmission rate did not differ between the two groups (23.5%, CI 13.8 to 38.5, in the BC group and 24.8%, CI 15.0 to 39.6, in the placebo group at 15 months). Similarly, there was no difference in mortality at 15 months (22.9%, CI 13.7 to 36.9, in the BC group and 16.5%, CI 9.0 to 29.4, in the placebo group)., Conclusion: This analysis failed to suggest any benefit of BC disinfection on mother to child HIV transmission or perinatal and infant mortality.

Objective: To study the relationship between maternal plasma RNA levels and mother-to-child transmission (MTCT) of HIV-1 in African breastfed children., Design: Nested case-control study within a randomized trial assessing the efficacy of a short maternal zidovudine (ZDV) regimen to reduce MTCT., Methods: Eligible women received either 300 mg of ZDV twice a day until labour, 600 mg at the beginning of labour and 300 mg twice a day for 7 days post-partum or a placebo. The diagnosis of paediatric HIV-1 infection was based on PCR tests at days 1--8, 45, 90 and 180 then on serology performed at 3 monthl intervals. Plasma HIV-1 RNA was measured at inclusion and on day 8 after delivery for all women who did transmit HIV to their children (cases) using a Chiron branched DNA assay (sensitivity 50 copies/ml) and compared with women who did not transmit (two per case) matched for phase trial, treatment allocation and site., Results: At inclusion, mean log10 viral load was 4.6 among 55 transmitting mothers and 3.7 among 117 non transmitters (P = 0.0001). Among transmitters, the mean difference in log10 viral load between day 8 post-partum and inclusion was -0.13 in the ZDV group (n = 23) versus 0.27 in the placebo group (n = 32; P = 0.01); among non transmitters it was -0.35 for the ZDV group (n = 47) versus 0.27 in the placebo group (n = 70; P < 10(-4)). In multivariate logistic regression analysis, odds ratios for MTCT were 8.7 (95% confidence interval, 3.7-20.6) for 1 log(10) increase of maternal RNA at inclusion and 4.2 (95% confidence interval, 1.7--10.3) for 1 log(10) increase difference from inclusion to day 8 post-partum., Conclusion: High maternal viral load at inclusion strongly predicts MTCT of HIV in Africa. A short ZDV treatment regimen decreases significantly maternal viral load from its pretreatment level.

Breast milk transmission of HIV-1 can occur at any time during the entire duration of breastfeeding. The risk of late postnatal transmission (after 2.5 months of age) is 3.2 per 100 child/years of breastfeeding, but early postnatal transmission may be more frequent than previously thought. Exclusive breastfeeding has been suggested to be less risky than mixed feeding. Breast milk contains immunoactive cells, antiinfectious substances, immune globulins, cytokines, and complement factors. HIV-1 has been found in breast milk from HIV-infected mothers as both cell-associated and cell-free particles. Mastitis has been suggested to facilitate transmission of HIV-1. The portal of entry of HIV-1 in the infant mucosae may involve tonsilar lymphoepithelium, M cells, and enterocytes from intestinal surfaces. Anti-HIV-1 SIgA and IgM in breast milk and intestinal fluid may confer some protection. Transmission of HIV-1 by breastfeeding has to be taken into account in designing interventions to reduce/prevent mother-to-child transmission in developing countries.

Objectives: Different approaches to prevent mother-to-child transmission of HIV are being evaluated in developing countries. The first trials using a short regimen of zidovudine have been successful in Thailand, Côte d'Ivoire and Burkina Faso. International and local strategies are now being considered. The Ghent International Working Group on Mother-to-Child Transmission of HIV developed public health policy options to integrate these interventions into basic and maternal and child health (MCH) services., Methods: The following tasks were undertaken: a critical review of randomized trials; an international pooled analysis of late postnatal transmission of HIV through breastfeeding; a review of the cost-effectiveness and cost-benefit of antiretroviral prophylaxis; a feasibility assessment of preventive strategies, including a postal survey on HIV voluntary counselling and testing (VCT) of pregnant women; the identification of requirements and research priorities for prenatal, obstetric and paediatric care. These projects provided the background for a three-day workshop in Ghent, Belgium, in November 1997. Conclusions were further refined, based on 1998 research findings., Results: A summary of relevant evidence and ten public health recommendations are reported. VCT for pregnant women, a short regimen of zidovudine together with alternatives to breastfeeding currently represent the best option to reduce vertical transmission in most developing countries. The primary goal of the integrated package supporting these interventions is to alleviate overall maternal and infant morbidity and mortality., Conclusion: Prevention of mother-to-child transmission of HIV should now be considered for integration into basic health and MCH services of selected countries, with the involvement of governments and donor agencies.

Objectives: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection., Design: A randomized, double blinded phase II trial., Setting: Prenatal care units in Abidjan (Côte d'Ivoire) and Bobo-Dioulasso (Burkina Faso)., Patients: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were eligible. A total of 108 women (54 in each group) enrolled from November 1996 to April 1997, with their informed consent., Intervention: Women self administered daily a vaginal suppository of 1% benzalkonium chloride or matched placebo from 36 weeks of pregnancy, and a single intrapartum dose. The neonate was bathed with 1% benzalkonium chloride solution or placebo within 30 minutes after birth., Main Outcome Measures: Adverse events were recorded weekly, with a questionnaire and speculum examination in women through delivery, and examination of the neonate through day 30. The incidence of genital signs and symptoms in the women and cutaneous or ophthalmological events in newborns were compared between groups on an intent to treat basis., Results: The median duration of prepartum treatment was 21 days (range 0-87 days). Compliance was 87% for prepartum and 69% for intrapartum treatment, and 88% for the neonatal bath, without differences between the two groups. In women, the most frequent event was leucorrhoea; the incidence of adverse events did not differ between treatment groups. In children, the incidence of dermatitis and conjunctivitis did not differ between the benzalkonium chloride and placebo groups (p = 0.16 and p = 0.29, respectively)., Conclusion: Vaginal disinfection with benzalkonium chloride is a feasible and well tolerated intervention in west Africa. Its efficacy in preventing vertical HIV transmission remains to be demonstrated.

Objectives: to study different parameters of humoral immunity responses in the serum of 39 human immunodeficiency virus type-1 infected pregnant women from Kigali, (Rwanda) in correlation with perinatal transmission., Methods: this study was done between 1988 and 1994. Thirty nine HIV-1 infected women, 18 transmitting (T) and 21 non-transmitting (NT) mothers, have been chosen based on the quantity of sera available for analysis. Maternal data were collected at the time of delivery or during the preceding month. Quantification of viral load was performed by the signal amplification bDNA assay. Specific reactivity of antibody was tested against recombinant p24 protein and five different synthetic peptides from gp120 and gp41 based on HIV LAI-strain sequences. Neutralization assays were performed against laboratory (RII strain of the HIV-1 C subtype) and primary strains (two NSI and one SI of the HIV-1 A subtype). Antibody Dependent Cellular Cytotoxicity assay was performed with CEM.NK(R) cells against a laboratory HIV-1 strain., Results: absence of correlation regarding maternal viral load, or viral subtype and vertical transmission was observed. By contrast, the CD4/CD8 ratio was significantly higher in non-transmitting mothers compared to transmitting mothers. Moreover, high anti-p24 antibody avidity was correlated with a lower risk of perinatal transmission. Furthermore, transmission risk appeared significantly higher with reactivity of serum samples to linear epitopes of gp41 (amino acids 566-582, 578-594), whereas risk appeared lower with reactivity to the immunodominant domain of gp41 (amino acids 597-609). No significant difference was observed in titres of antibody neutralizing primary isolates (two NSI (non syncitium inducer) and one SI (syncitium inducer) of the HIV-1 A subtype) and laboratory strain (RII strain, of the HIV-1 C subtype) between transmitting and non-transmitting mother's sera. In addition, titres of Antibody Dependent Cellular Cytotoxicity were similar in transmitting versus non-transmitting mothers. However, high Antibody Dependent Cellular Cytotoxicity titres were correlated with a good clinical status of children., Conclusions: three parameters such as high CD4/CD8 ratio, high anti-p24 antibody avidity and high reactivity against the immunodominant epitope of gp41 have been shown to be correlated with no perinatal transmission. High Antibody Dependent Cellular Cytotoxicity titres appeared to be linked to a good clinical status of children after birth. One parameter, reactivity against two linear epitopes of gp41, appeared to be correlated with vertical transmission.

Background: Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed populations. We assessed the acceptability, tolerance, and 6-month efficacy of a short regimen of oral zidovudine in African populations practising breastfeeding., Methods: A randomised double-blind placebo-controlled trial was carried out in public clinics of Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso. Eligible participants were women aged 18 years or older, who had confirmed HIV-1 infection and pregnancy of 36-38 weeks duration, and who gave written informed consent. Exclusion criteria were severe anaemia, neutropenia, abnormal liver function, and sickle-cell disease. Women were randomly assigned zidovudine (n=214; 300 mg twice daily until labour, 600 mg at beginning of labour, and 300 mg twice daily for 7 days post partum) or matching placebo (n=217). The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1-8, 45, 90, and 180. We compared the probability of infection at a given age in the two groups. Analyses were by intention to treat., Findings: Women were enrolled between September, 1995, and February, 1998, when enrolment to the placebo group was stopped. Analysis was based on 421 women and 400 lifeborn infants. Baseline demographic, clinical, and laboratory characteristics were similar in the two groups. The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0% in the zidovudine group (n=192) and 27.5% in the placebo group (n=197; relative efficacy 0.38 [95% CI 0.05-0.60]; p=0.027). Adjustment for centre, period of recruitment, mode of delivery, maternal CD4-cell count, duration of labour, prolonged rupture of membranes, and duration of breastfeeding did not change the treatment effect. The proportions of women taking more than 80% of the planned maximum dose were 75% before delivery, 81% during labour, and 83% post partum, without statistical difference between the groups. No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group., Interpretation: A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated, and provides a 38% reduction in early vertical transmission of HIV-1 infection despite breastfeeding.

Background: An understanding of the risk and timing of mother-to-child transmission of HIV-1 in the postnatal period is important for the development of public-health strategies. We aimed to estimate the rate and timing of late postnatal transmission of HIV-1., Methods: We did an international multicentre pooled analysis of individual data from prospective cohort studies of children followed-up from birth born to HIV-1-infected mothers. We enrolled all uninfected children confirmed by HIV-1-DNA PCR, HIV-1 serology, or both. Late postnatal transmission was taken to have occurred if a child later became infected. We calculated duration of follow-up for non-infected children from the time of negative diagnosis to the date of the last laboratory follow-up, or for infected children to the mid-point between the date of last negative and first positive results. We stratified the analysis for breastfeeding., Findings: Less than 5% of the 2807 children in four studies from industrialised countries (USA, Switzerland, France, and Europe) were breastfed and no HIV-1 infection was diagnosed. By contrast, late postnatal transmission occurred in 49 (5%) of 902 children in four cohorts from developing countries, in which breastfeeding was the norm (Rwanda [Butare and Kigali], Ivory Coast, Kenya), with an overall estimated risk of 3.2 per 100 child-years of breastfeeding follow-up (95% CI 3.1-3.8), with similar estimates in individual studies (p=0.10). Exact information on timing of infection and duration of breastfeeding was available for 20 of the 49 children with late postnatal transmission. We took transmission to have occurred midway between last negative and first positive HIV-1 tests. If breastfeeding had stopped at age 4 months transmission would have occurred in no infants, and in three if it had stopped at 6 months., Interpretation: Risk of late postnatal transmission is consistently shown to be substantial for breastfed children born to HIV-1-positive mothers. This risk should be balanced against the effect of early weaning on infant mortality and morbidity and maternal fertility.

Mother to child transmission (MCT) of Human Immunodeficiency Virus (HIV) is the main cause of the spread of the HIV epidemic in the pediatric population. It is estimated that to date, three million children worldwide have been infected by HIV. The epidemic burden in developing countries is dramatic. Ninety-five percent of the world's HIV-infected women are living in developing countries. In industrialized countries, antiretroviral treatment of pregnant women and newborns with azidothymidine (AZT, ACTG 076 regimen) and discouraging breast feeding by HIV-infected mothers are effectively reducing MCT of HIV. However, there are three major obstacles to the systematic application of these strategies in developing countries: (a) difficulties in implementing the complex AZT administration and its corollary the avoidance of breast feeding; (b) the complexity of the logistics of the ACTG 076 regimen; (c) cost. Indeed, in developing countries the socioeconomic situation of the populations are precarious and health structures and services are underdeveloped. In addition, the anxiety and the reluctance of general population in the face of the HIV problem and the high prevalence of maternal anemia reduce the acceptability and safety of AZT treatment for pregnant women in developing regions. Only interventions that are applicable, acceptable, safe, affordable, of low cost and integrated into health system will be able to reduce HIV MCT. We now know that MCT occurs mostly during the perinatal period and the maternal viral load in blood, in cervical secretions and in breast milk appears to be the main determinant of transmission. Maternal vitamin A deficiency may also favor MCT of HIV. It is however possible that this association is confounded by the relationship between advanced maternal HIV disease (a known risk factor for transmission) and vitamin A deficiency. In spite of these uncertainties concerning determinants of MCT of HIV, several interventions have been designed. The first involves treating the mother with antiretroviral drugs for the perinatal period. The second is vaginal disinfection by application of virucidal antiseptics during the perinatal period. The third is to give vitamin A supplements to pregnant women and children. Finally, passive immunotherapy with anti-HIV antibodies applied to pregnant women and/or new born, may be beneficial. The feasibility, safety and efficacy of these potential interventions have not yet been demonstrated in developing countries. In view of the dramatic spread of HIV infection in these countries, the evaluation of these interventions is of utmost priority. These trials are necessary because of the public health emergency but should be performed in strict respect of human rights and medical ethics.

Would HIV-1-positive pregnant African women use interventions of AIDS testing, medication (oral or vaginal), and vaginal disinfection to reduce the likelihood of HIV-1 transmission to their child? In this pilot study in two west African cities (Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina Faso), social workers gave a native-language questionnaire to 607 pregnant women at four Maternal and Child Health Centers. The women were asked about their perception of the HIV test; consequences of testing and counseling; choice of medical intervention to protect the future child; and feelings about being in a randomized, placebo-controlled, clinical trial. Most accepted the principle of an AIDS test, said they wanted the agreement of their regular partner before being tested, and would use interventions to reduce the risk of vertical transmission. The researchers concluded that although concepts of informed consent, randomization, and placebo are difficult to understand, the study results are promising and encourage the evaluation of clinical trials to reduce mother-to-child transmission of HIV-1 in Africa.

Human milk has been considered only recently as a source of transmission for the human immunodeficiency virus. The estimated postnatal transmission rate from mothers who acquired human immunodeficiency virus infection while lactating is 26% (95% confidence interval 13% to 39%) and may be in the range of 8% to 18% from mothers who were infected before becoming pregnant. Risk factors for postnatal transmission include maternal immune deficiency and the presence of human immunodeficiency virus-infected cells in milk. Some milk factors may be protective against postnatal transmission such as specific immunoglobulin A and immunoglobulin M and a molecule able to inhibit the binding of human immunodeficiency virus to CD4. In addition to its safety and its birth-spacing properties, breast-feeding provides immunologic protection and an ideal nutritional content to the infant. In a poor hygienic environment artificial feeding dramatically increases morbidity and mortality from diarrheal diseases and respiratory infections. Consequently, according to our current knowledge the World Health Organization and the United Nations Children's Fund reasonably recommend continuing breast-feeding promotion in women living in settings where infectious diseases and malnutrition are the primary causes of infant deaths such as in many developing countries. In settings where infectious diseases and malnutrition are not the primary causes of infant deaths, such as in most of the settings in the developed world, the advisory group recommends against breast-feeding for mothers with proved human immunodeficiency virus-1 infection.