Factors influencing breast milk HIV RNA viral load among Zambian women

In a longitudinal cohort study we investigated factors contributing to breast milk HIV RNA viral load among lactating women in Lusaka, Zambia. Detailed data from 135 HIV-infected women were collected by questionnaires concerning postpartum maternal and infant health and infant feeding practice. Maternal blood was collected during pregnancy and at 6 weeks postpartum. Milk samples collected from each breast at 10 days and 6 weeks postpartum plus a subset collected at other time points were analyzed for HIV RNA viral load. Increased milk viral load was associated in univariate analyses with maternal symptoms of poor health, raised plasma alpha(1)-acid glycoprotein (AGP) at week 6, raised milk sodium/potassium (Na/K) ratio, postpartum need for antibiotics, preterm delivery, and low birth weight infants. In a multiple regression 49% of variability in mean milk viral load was explained by milk Na/K ratio and need for antibiotics, with borderline contributions from plasma AGP and plasma viral load. Maternal blood hemoglobin or receipt of iron supplements and infant feeding variables such as changing the infant's diet by moving from exclusive to nonexclusive breastfeeding or adding solid foods were not associated with milk viral load. Thus maternal health was the main factor contributing to milk viral load. The lack of effect of feeding practices on milk viral load and the previously determined association of poor maternal health with reduced duration of exclusive breastfeeding in this cohort suggest the relation between exclusive breastfeeding and decreased HIV transmission may be secondary to poor maternal health.     

Infant Feeding Practices were not Associated with Breast Milk HIV-1 RNA Levels in a Randomized Clinical Trial in Botswana

Exclusive breastfeeding has been associated with a reduced risk of late vertical HIV transmission as compared to an infant diet composed of breast milk mixed with supplemental foods or liquids. Hypothesized mechanisms include increased infectivity of breast milk from mothers who practice mixed breastfeeding (MBF), or mechanisms such as increased gastrointestinal permeability in the infant caused by mixed feeding. It has been proposed that MBF may result in subclinical mastitis and higher breast milk HIV titers. However, little is known about the relationship between feeding strategy and breast milk viral load. We measured the HIV-1 concentration in breast milk in a sub-cohort of women enrolled in a mother-to-child HIV transmission prevention trial (the "Mashi" study). We report no observed relationship between MBF and measured breast milk viral RNA load. Our findings suggest that the increased transmission risk associated with higher breast milk HIV-1 RNA during MBF is unlikely.     

Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission

Alpha-defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of alpha-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined < 48 h after birth and at months 1, 3, 6, 9, and 12. Breast milk specimens collected at month 1 were assayed for alpha-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected alpha-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable alpha-defensins (> or =50 pg/ml) had a median concentration of 320 pg/ml and significantly higher mean breast milk HIV-1 RNA levels than women with undetectable alpha-defensins (2.9 log(10) copies/ml versus 2.5 log(10) copies/ml, p = 0.003). Increased alpha-defensins concentrations in breast milk were also associated with subclinical mastitis (Na (+)/K(+) ratio > 1) and increased breast milk chemokine levels. Overall, 40 (15%) infants were HIV-1 uninfected at birth and subsequently acquired HIV-1. There was no significant association between month 1 alpha-defensins and risk of HIV-1 transmission. In conclusion, alpha-defensins were associated with breast milk HIV-1 viral load, chemokine levels, and subclinical mastitis, all of which may alter risk of infant HIV-1 acquisition. Despite these associations there was no significant relationship between breast milk alpha-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.     

CC and CXC chemokines in breastmilk are associated with mother-to-child HIV-1 transmission

INTRODUCTION: CC and CXC chemokines may play a role in mother-to-child HIV-1 transmission by blocking HIV-1 binding to chemokine receptors and impeding viral entry into cells. METHODS: To define correlates of breastmilk chemokines and associations with infant HIV-1 acquisition, chemokines in breastmilk and infant HIV-1 infection risk were assessed in an observational, longitudinal cohort study. We measured MIP-1alpha, MIP-1beta, RANTES, and SDF-1 in month 1 breastmilk specimens from HIV-1-infected women in Nairobi and HIV-1 viral load was calculated in maternal plasma and breastmilk at delivery and 1 month postpartum. Infant infection status was determined at birth and months 1, 3, 6, 9, and 12. RESULTS: Among 281 breastfeeding women, 60 (21%) of their infants acquired HIV-1 during follow-up, 39 (65%) of whom became infected intrapartum or after birth. MIP-1alpha, MIP-1beta, RANTES, and SDF-1 were all positively correlated with breastmilk HIV-1 RNA (P<0.0005). Women with clinical mastitis had 50% higher MIP-1alpha and MIP-1beta levels (P<0.001 and P=0.006, respectively) and women with subclinical mastitis (breastmilk Na(+)/K(+)>1) had approximately 70% higher MIP-1alpha, MIP-1beta and RANTES (P<0.002 for all) compared to women without mastitis. Independent of breastmilk HIV-1, increased MIP-1beta and SDF-1 were associated with reduced risk of infant HIV-1 (RR=0.4; 95% CI 0.2-0.9; P=0.03 and RR=0.5; 95% CI=0.3-0.9; P=0.02, respectively) and increased RANTES was associated with higher transmission risk (RR=2.3; 95% CI 1.1- 5.3; P=0.04). CONCLUSIONS: These observations suggest a complex interplay between virus levels, breastmilk chemokines, and mother-to-child HIV-1 transmission and may provide insight into developing novel strategies to reduce infection across mucosal surfaces.     

Epidemiology and microbiology of subclinical mastitis among HIV-infected women in Malawi

The epidemiology and microbiology of subclinical mastitis, a risk factor for perinatal HIV transmission, have not been well characterized. In all, 250 HIV-infected women were followed from two weeks to 12 months postpartum in Blantyre, Malawi, and subclinical mastitis was assessed by breast milk leukocyte counts. The point prevalence of subclinical mastitis at 2, 4, 6, 10, and 14 weeks, and 6, 9, and 12 months was 12.2%, 7.8%, 6.8%, 3.7%, 10.6%, 5.1%, 4.9%, and 1.9%, respectively (P = 0.002), and 27.2% of women had at least one episode of subclinical mastitis. There was no significant relationship between maternal plasma HIV load or parity and subclinical mastitis. Staphylococcus aureus was isolated in 30% of women with subclinical mastitis, and the proportion of women with positive cultures decreased during follow-up (P = 0.02). Subclinical mastitis is prevalent among breastfeeding mothers and further studies are needed to characterize the differences between infectious and non-infectious subclinical mastitis.     

Early growth of infants of HIV-infected and uninfected Zambian women

OBJECTIVE: Parental HIV infection may affect even those exposed children who remain uninfected. We investigated early growth, an indicator of overall health, of infants born to Zambian mothers recruited for a study of breastfeeding and postpartum health. METHODS: HIV-infected and uninfected women in Lusaka were followed regularly from late pregnancy to 16 weeks postpartum. Infant weight and length were measured at birth, 6 and 16 weeks. Infant HIV status could not be specifically determined in this cohort so comparisons were between all infants of HIV-uninfected mothers (n = 184) and those infants of HIV-infected mothers who were known to be alive and showed no clinical evidence of HIV infection at age 2-4 years (n = 85). RESULTS: Most infants were exclusively or predominantly breastfed until 16 weeks. At all time points infants of HIV-infected mothers tended to have lower weight and length standard deviation (Z) scores (significant for weight at 6 weeks; P = 0.04), even after adjustment for their lower gestational age at birth, compared with infants of uninfected mothers. In multivariate analyses the major factors affecting weight or length at 6 or 16 weeks of age were birth weight or length, and maternal subclinical mastitis, primiparity and weight during pregnancy. CONCLUSIONS: Early growth of infants of HIV-infected mothers is less than that of uninfected mothers, in part associated with subclinical mastitis, and this effect cannot be overcome with intensive support of mothers to follow international recommendations regarding exclusive breastfeeding.     

Laboratory indicators of mastitis are not associated with elevated HIV-1 DNA loads or predictive of HIV-1 RNA loads in breast milk

BACKGROUND: Mother-to-child transmission (MTCT) of HIV-1 has been associated with symptomatic and asymptomatic mastitis and with the quantity of HIV-1 RNA and DNA in maternal milk. An improved understanding of the relationship between indicators of inflammation and HIV-1 loads in breast milk could improve MTCT prevention strategies. METHODS: In a cross-sectional study, laboratory indicators of mastitis (breast milk sodium [Na(+)] concentration, sodium : potassium ratio [Na(+) : K(+)], and leukocyte count) were related to breast milk HIV-1 RNA and DNA loads and were evaluated for predicting viral loads in milk. RESULTS: Mastitis was present in 63 (15%) of 407, 60 (15%) of 407, and 76 (18%) of 412 milk specimens, as defined by Na(+) concentration >12 mmol/L, Na(+) : K(+) >1, and total leukocyte counts > or =10(6) cells/mL, respectively. Each indicator was associated with an increased milk HIV-1 RNA load (P<.05) but not with HIV-1 DNA load. Neutrophils correlated better with milk HIV-1 RNA load than total leukocytes. However, neither neutrophil count, Na(+) concentration, nor Na(+) : K(+) displayed a threshold that was both sensitive and specific for the detection of HIV-1 RNA in milk at thresholds of > or =50 or > or =10(4) copies/mL. CONCLUSIONS: HIV-1 DNA loads in breast milk were not increased during mastitis. Neither milk cell counts nor electrolyte concentrations were useful predictors of milk HIV-1 RNA or DNA loads for individual women.     

Impact of chloroquine on viral load in breast milk

The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P = 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding.     

Reduced mother-to-child transmission of HIV associated with infant but not maternal GB virus C infection

BACKGROUND: Prolonged coinfection with GB virus C (GBV-C) has been associated with improved survival in human immunodeficiency virus (HIV)-infected adults. We investigated whether maternal or infant GBV-C infection was associated with mother-to-child transmission (MTCT) of HIV-1 infection. METHODS: The study population included 1364 HIV-infected pregnant women enrolled in 3 studies of MTCT of HIV in Bangkok, Thailand (the studies were conducted from 1992-1994, 1996-1997, and 1999-2004, respectively). We tested plasma collected from pregnant women at delivery for GBV-C RNA, GBV-C antibody, and GBV-C viral genotype. If GBV-C RNA was detected in the maternal samples, the 4- or 6-month infant sample was tested for GBV-C RNA. The rates of MTCT of HIV among GBV-C-infected women and infants were compared with the rates among women and infants without GBV-C infection. RESULTS: The prevalence of GBV-C RNA in maternal samples was 19%. Of 245 women who were GBV-C RNA positive, 101 (41%) transmitted GBV-C to their infants. Of 101 infants who were GBV-C RNA positive, 2 (2%) were infected with HIV, compared with 162 (13%) of 1232 infants who were GBV-C RNA negative (odds ratio [OR] adjusted for study, 0.13 [95% confidence interval {CI}, 0.03-0.54]). This association remained after adjustment for maternal HIV viral load, receipt of antiretroviral prophylaxis, CD4(+) count, and other covariates. MTCT of HIV was not associated with the presence of GBV-C RNA (adjusted OR [aOR], 0.94 [95% CI, 0.62-1.42]) or GBV-C antibody (aOR, 0.90 [95% CI, 0.54-1.50]) in maternal samples. CONCLUSIONS: Reduced MTCT of HIV was significantly associated with infant acquisition of GBV-C but not with maternal GBV-C infection. The mechanism for this association remains unknown.     

British HIV Association and Children's HIV Association position statement on infant feeding in the UK 2011

To prevent the transmission of HIV infection during the postpartum period, the British HIV Association and Children's HIV Association (BHIVA/CHIVA) continue to recommend the complete avoidance of breast feeding for infants born to HIV-infected mothers, regardless of maternal disease status, viral load or treatment.     

Correlates of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission: association with maternal plasma HIV-1 RNA load, genital HIV-1 DNA shedding, and breast infections

To determine the effects of plasma, genital, and breast milk human immunodeficiency virus type 1 (HIV-1) and breast infections on perinatal HIV-1 transmission, a nested case-control study was conducted within a randomized clinical trial of breast-feeding and formula feeding among HIV-1-seropositive mothers in Nairobi, Kenya. In analyses comparing 92 infected infants with 187 infants who were uninfected at 2 years, maternal viral RNA levels >43,000 copies/mL (cohort median) were associated with a 4-fold increase in risk of transmission (95% confidence interval [CI], 2.2-7.2). Maternal cervical HIV-1 DNA (odds ratio [OR], 2.4; 95% CI, 1.3-4.4), vaginal HIV-1 DNA (OR, 2.3; 95% CI, 1.1-4.7), and cervical or vaginal ulcers (OR, 2.7; 95% CI, 1.2-5.8) were significantly associated with infant infection, independent of plasma virus load. Breast-feeding (OR, 1.7; 95% CI, 1.0-2.9) and mastitis (relative risk [RR], 3.9; 95% CI, 1.2-12.7) were associated with increased transmission overall, and mastitis (RR, 21.8; 95% CI, 2.3-211.0) and breast abscess (RR, 51.6; 95% CI, 4.7-571.0) were associated with late transmission (occurring >2 months postpartum). Use of methods that decrease infant exposure to HIV-1 in maternal genital secretions or breast milk may enhance currently recommended perinatal HIV-1 interventions.     

Virologic response to potent antiretroviral therapy and modeling of HIV dynamics in early pediatric infection

BACKGROUND: Human immunodeficiency virus (HIV) infection in infancy features a persistently high viral load and elevated antiretroviral drug clearance rates, which pose significant therapeutic challenges to the clinician. Viral and cellular kinetic analyses performed in HIV-infected adults have yielded significant insights into the dynamic setting of this viral infection. Similar studies are needed in pediatric populations, in whom differing dynamics might translate into age-specific treatment approaches. METHODS: Viral and cellular kinetic analyses were performed using a nonlinear mixed-effects model in a cohort of 48 infants 1-24 months of age enrolled in a trial of ritonavir-based highly active antiretroviral therapy (HAART). RESULTS: Infected cell compartment kinetics were comparable with reported adult values, with no age-specific differences demonstrated--suggesting the ability to suppress viral replication in infants receiving HAART. Comparisons between 2 ritonavir dosing schedules revealed significant improvement in phase 1/2 decay constants in favor of the higher dose. A negative correlation was established between plasma RNA levels and phase 1 decay rates, which has worrisome implications for infant therapeutics given high infant pretreatment plasma virus levels. CONCLUSIONS: Ritonavir-based HAART regimens in infancy result in HIV decay constants comparable to those reported in adults, without age-specific variability. Despite higher plasma HIV levels and CD4 lymphocyte counts in infancy, HAART can result in timely, effective control of viral replication.     

Exposure to HIV-1 during delivery and mother-to-child transmission

BACKGROUND: The correlation between the presence of HIV-1 in maternal cervicovaginal secretions and in the infant's oro-pharyngal secretions at birth, and mother-to-child HIV transmission (MTCT) were examined to obtain a better understanding of its mechanism. METHODS: Women without medical and obstetrical complications, living within a reasonable distance of the government hospital in Mombasa, Kenya, were recruited after informed consent. Maternal and infant characteristics were collected. Polymerase chain reaction was used to detect HIV-1 in cervico-vaginal and oro-pharyngal secretions. Infants were tested for HIV-1 by polymerase chain reaction within 48 h and at 6 weeks after delivery. RESULTS: Between April 1998 and April 1999, 228 woman-infant pairs were included in the study. HIV-1 DNA in cervico-vaginal secretions was independently associated with HIV-1 maternal viral load and with infant birth-weight, whereas HIV-1 RNA was associated with maternal viral load and maternal age. HIV-1 DNA in the oropharyngal secretions was also independently associated with maternal viral load. MTCT rate at the age of 6 weeks was 23.6%. Intrapartum and early postpartum HIV transmission was independently associated with maternal viral load [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI),1.0-2.7], detection of HIV-1 RNA in cervico-vaginal secretions (adjusted OR, 3.2; 95% CI, 1.5-7.3) and of HIV-1 DNA in oro-pharyngeal secretions (adjusted OR, 3.2; 95% CI, 1.1-9.0). DISCUSSION: As far as is known, this is the first study showing that infant exposure to HIV-1 in the birth canal and the presence of HIV-infected cells in the infant's oropharyngeal cavity are independently associated with intrapartum and early postpartum MTCT. It supports the hypothesis that MTCT could occur through the oral route.     

Influence of body mass index on pregnancy outcomes among HIV-infected and HIV-uninfected Zambian women

OBJECTIVES: To determine the influence of body mass index (BMI) on pregnancy outcomes of HIV-infected and HIV-uninfected Zambian women and to assess the possible role of BMI on mother-to-child transmission rate of HIV. METHODS: We analysed data from a clinical trial on nevirapine administration for the prevention of mother-to-child transmission of HIV in Lusaka, Zambia. Demographic characteristics, medical information and pregnancy outcomes were used in this secondary analysis. RESULTS: A total of 1211 women were included in this analysis and 36% were HIV-infected. Among HIV-infected women, maternal parity and prior stillbirths increased with increasing BMI in univariate analysis. Mean birth weight rose as well at 28.3 g [95% confidence interval (CI)=14.0-42.6] of infant weight per BMI unit. Transmission of HIV from mother to child appeared inversely related to BMI when compared according to BMI quartile (P for trend=0.07). In the HIV-uninfected group, infant birth weight increased with increasing BMI, at 32.7 g (95% CI=23.5-41.9) of infant weight per BMI unit. CONCLUSION: Birth weight increased alongside BMI in both HIV-infected and HIV-uninfected women. There is a suggestion that women with lower BMI have a greater risk of perinatal HIV transmission, even after adjustments for HIV viral load and CD4 count.     

Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi

OBJECTIVE: To determine the association between maternal syphilis and HIV mother-to-child transmission (MTCT). DESIGN: Prospective cohort study. METHODS: Pregnant women admitted at Queen Elizabeth Central Hospital (Malawi) in late third trimester were screened for HIV (by HIV rapid tests) and syphilis (by rapid plasma regain test and Treponema pallidum hemagglutination assay). HIV-infected women and their infants received nevirapine, according to the HIVNET 012 protocol. They were followed up at 6 and 12 weeks postpartum. Infant HIV infection was diagnosed by DNA PCR. FINDINGS: Of the 1155 HIV-infected women enrolled, 1147 had syphilis test results, of whom 92 (8.0%) were infected. Only 751 HIV-positive women delivered live singleton infants who were tested for HIV at birth. Of these, 65 (8.7%) were HIV-infected, suggesting in utero (IU) HIV MTCT. Of the 686 infants who were HIV-negative at birth, 507 were successfully followed up. Of these, 89 (17.6%) became HIV-infected, suggesting intrapartum/postpartum (IP/PP) HIV MTCT. Maternal syphilis was associated with IU HIV MTCT, after adjusting for maternal log10 HIV-1 viral load and low birth weight (LBW) [adjusted relative risk (ARR), 2.77; 95% CI, 1.40-5.46]. Furthermore, maternal syphilis was associated with IP/PP HIV MTCT (ARR, 2.74; 95% CI, 1.58-4.74), after adjusting for recent fever, breast infection, LBW and maternal log10 HIV-1 viral load. CONCLUSION: Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections.     

Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease

Transmission of human immunodeficiency virus type 1 (HIV-1) via breast-feeding can occur throughout lactation. Defining both fluctuation in breast-milk virus level over time and how breast-milk virus correlates with mother-to-child transmission is important for establishing effective interventions. We quantified breast-milk HIV-1 RNA levels in serial samples collected from 275 women for up to 2 years after delivery. Higher maternal plasma virus load, lower maternal CD4 T cell count, and detection of HIV-1 DNA in maternal genital secretions were significantly associated with elevated breast-milk HIV-1 RNA. Within women who breast-fed, median virus load in colostrum/early milk was significantly higher than that in mature breast milk collected 14 days after delivery (P< or =.004). Breast-feeding mothers who transmitted HIV-1 to their infants had both significantly higher breast-milk viral RNA throughout lactation and more-consistent viral shedding, compared with mothers who did not transmit HIV-1. In breast-feeding women, a 2-fold-increased risk of transmission was associated with every 10-fold increase in breast-milk virus load (95% confidence interval, 1.3-3.0; P<.001). These results indicate that the risk of infant infection from breast-feeding is influenced by breast-milk virus load, which is highest early after delivery.     

Gag-p6 Tsg101 binding site duplications in maternal-infant HIV infection

Prevalence and patterns of HIV p6 duplications in HIV-1 mother-to-baby transmission are examined. Resistance genotyping was performed in a multisite U.S. study of antiretroviral resistance in vertical transmission. Sequence data were used in secondary analyses of HIV genetic variation. Two hundred sixty HIV viral RNA samples from HIV-infected pregnant women and their infants were analyzed with a commercial resistance genotyping kit. Chromatograms were examined for variability in the 3' region of gag. From 103 mother-baby sets, 190 samples gave readable p6 sequence. Of 103 mother-baby sets, 20 (19%) showed duplication of between 3 and 12 codons ending at the PTAPP motif of p6. When maternal p6 duplication was present and the p6 sequence was available from both maternal and infant isolates, all (seven of seven) infants had p6 duplications, but two cases showed discordancies between maternal and infant sequences. The prevalence of p6 duplication varied among geographical sites, ranging from 4 of 43 families (9%, Puerto Rico and New York sites) to 16 of 60 families (27%, Massachusetts, Texas, and Illinois). The presence of p6 duplication was not associated with differences in transmission, viral load, or disease progression in the infants, but showed a trend toward association with lower maternal CD4 count. Substantial p6 variation data are generated by resistance genotyping. PTAP duplication is prevalent in this group of HIV-infected women and infants. The duplication is efficiently transmitted from mother to infant, is present at variable prevalence at different geographic sites, and shows no clear association with vertical transmission risks.     

Prevention of mother-to-child transmission of HIV infection

PURPOSE OF REVIEW: Mother-to-child transmission of HIV infection is the primary cause of paediatric HIV infections worldwide. Although clinical trials show that antiretroviral therapy, elective caesarean section and formula feeding can significantly reduce the peripartum or postpartum risk of transmission, their application on a population basis is challenging. There is a need for alternative, easier and more effective interventions for population-based programmes. RECENT FINDINGS: This review addresses recent advances in our understanding of mother-to-child transmission risk factors, including maternal viral load (in plasma, genital tract and breast milk) and gender, and determinants and rates of postnatal transmission. New information on prophylactic antiretroviral therapy includes results from randomized trials in Africa and Thailand, in addition to new information on implementation of prevention of mother-to-child transmission programmes in nontrial settings, in both developed and developing countries. Two important issues relating to use of antiretroviral prophylaxis are discussed: safety and toxicity, including new findings on haemopoiesis, prematurity and mitochondrial abnormalities in antiretroviral therapy-exposed infants and children, and resistance. Recent trends and controversies relating to mode of delivery in HIV-infected pregnant women are outlined. Regarding infant feeding, preliminary results on use of mono-antiretroviral therapy to prevent postnatal transmission in breastfeeding HIV-exposed infants are discussed. SUMMARY: In resource-rich settings, virtual elimination of mother-to-child transmission is theoretically possible. Even in these settings, however, a substantial number of infected women are not being identified early enough for optimum application of prevention of mother-to-child transmission interventions. In developing country settings, focus is being directed towards scaling-up prevention programmes now that trials have established a variety of effective antiretroviral prophylactic approaches.     

Breast health problems are rare in both HIV-infected and HIV-uninfected women who receive counseling and support for breast-feeding in South Africa.

BACKGROUND: Breast problems, including mastitis, can interfere with the duration and exclusivity of breast-feeding. However, there are no large prospective studies documenting the prevalence, duration, and timing of such problems in breast-feeding women, particularly those who are infected with human immunodeficiency virus (HIV). METHODS: Women enrolled prenatally underwent a breast-feeding counseling intervention until 6 months after delivery. Breast health problems were documented per breast for 180 days after delivery, with 14-day recall histories. RESULTS: Breast health problems were rare, and there were no significant differences between HIV-infected and HIV-uninfected women for any of the following conditions: engorgement, 39 HIV-infected women (3.5%) versus 33 HIV-uninfected women (2.7%; P=.30); breast thrush, 17 (1.5%) versus 12 (1.0%; P=.25); bleeding nipple, 6 (0.5%) versus 4 (0.3%; P=.45); and mastitis/abscess, 11 (1.0%) versus 6 (0.5%; P=.17). Most problems occurred during the first month after birth, with few additional mothers experiencing problems after this point: at 1 and 6 months, 13% and 17% of all mothers, respectively, had experienced a minor or major breast health problem, including sore nipples. Women who had not exclusively breast-fed their infants were more likely to experience any of the breast health problems than were women who had exclusively breast-fed their infants (time-dependent variable; adjusted odds ratio, 1.46; 95% confidence interval, 1.13-1.87; P=.003). HIV-infected women who experienced any serious breast health problem (i.e., bleeding nipple, pus oozing from a nipple or breast, or mastitis/abscess) were 3.55 times (95% confidence interval, 0.86-14.78 times; P=.08) more likely to transmit HIV postnatally to their infant. CONCLUSIONS: With encouragement to exclusively breast-feed, women experienced few breast health problems. When those problems did occur, HIV-infected women with bleeding nipple, pus oozing from a nipple or breast, or mastitis/abscess were more likely to transmit HIV to their infants.     

Predictive factors for immunological and virological endpoints in Thai patients receiving combination antiretroviral treatment

BACKGROUND: Routine CD4 count and HIV viral load monitoring is a financial barrier in developing countries. METHODS: We assessed factors associated with CD4 counts < or =200 cells/microL and detectable viral load in Thai HIV-infected patients receiving antiretroviral therapy (ART) at the HIV Netherlands Australia Thailand Research Collaboration and the Thai Red Cross AIDS Research Centre (HIV-NAT). Univariate and multivariate Cox proportional hazards models for multiple treatment failures were used to determine factors related to CD4 counts < or =200 cells/microL and detectable viral load. Multivariate Cox proportional hazards models for CD4 counts < or =200 cells/microL were developed with and without viral load in order to build models applicable to contexts in which viral load is not available. RESULTS: Four hundred and seventeen patients were included in the study. Fifty-four per cent were male, and the median CD4 count and log(10) viral load at baseline were 283 cells/microL and 4.3 log(10) HIV-1 RNA copies/mL, respectively. Independent factors related to CD4 count < or =200 cells/microL were CD4 count at baseline [hazards ratio (HR) 0.20/100 cells/microL; 95% confidence interval (CI) 0.17-0.23] and changes in CD4 count (HR 0.22/100 cells/microL; 95% CI 0.17-0.28). Factors in multivariate models (in which viral load was considered for inclusion) were CD4 count at baseline (HR 0.21/100 cells/microL; 95% CI 0.18-0.24), changes in CD4 count (HR 0.25/100 cells/microL; 95% CI 0.19-0.32) and detectable viral load (HR 1.94; 95% CI 1.20-3.13). Predictive factors (independent of viral load) were triple ART or highly active antiretroviral therapy (HAART) (HR 0.28; 95% CI 0.22-0.36) and detectable viral load at baseline (HR 2.96; 95% CI 2.24-3.91). Conclusions CD4 count at baseline and changes in CD4 count were important in predicting CD4 counts < or =200 cells/microL. Triple ART and detectable viral load at baseline were important in predicting detectable viral load.