Introduction

Early infant diagnosis (EID) of HIV infection is an important service to reduce paediatric morbidity and mortality related to HIV/AIDS. Although South Africa has a national EID programme based on PCR testing, there are no population-wide data on the linkage of infants testing HIV PCR-positive to HIV care and treatment services.

Methods

We conducted a retrospective analysis of all public sector laboratory data from across the Western Cape province between 2005 and 2011. We linked positive HIV PCR results to subsequent HIV viral load testing to determine the proportion of infants who were successfully linked to HIV care.

Results

A total of 83 698 unique infant HIV PCR tests were documented, of which 6322 (8%) were PCR positive. The proportion of PCR-positive children declined from 12% in 2005 to 3% in 2011. Of the children testing PCR-positive, 4105 (65%) had subsequent viral load testing indicating successful linkage to care. The proportion of successfully linked infants increased from 54% in 2005 to 71% in 2010, while the median delay in days to successful linkage decreased from 146 days in 2005 to 33 days in 2010.

Discussion

From 2005 to 2011 there has been a reduction in the proportion of children testing HIV PCR-positive, and an increase in the proportion of infected infants successfully linked to HIV care and treatment, in this setting. However a large proportion of infected infants remain unlinked to antiretroviral therapy services and there is a clear need for interventions to further strengthen EID programmes.

Background. The effect of herpes simplex virus type 2 (HSV-2) suppression on human immunodeficiency virus type 1 (HIV-1) RNA in the context of prevention of mother-to-child transmission (PMTCT) interventions is unknown.

Methods. Between April 2008 and August 2010, we conducted a randomized, double-blind trial of twice daily 500 mg valacyclovir or placebo beginning at 34 weeks gestation in 148 HIV-1/HSV-2 coinfected pregnant Kenyan women ineligible for highly active antiretroviral therapy (CD4 > 250 cells/mm3). Women received zidovudine and single dose nevirapine for PMTCT and were followed until 12 months postpartum.

Results. Mean baseline plasma HIV-1 RNA was 3.88 log10 copies/mL. Mean plasma HIV-1 was lower during pregnancy (−.56 log10 copies/mL; 95% confidence interval [CI], −.77 to −.34) and after 6 weeks postpartum (−.51 log10 copies/mL; 95% CI, −.73 to −.30) in the valacyclovir arm than the placebo arm. Valacyclovir reduced breast milk HIV-1 RNA detection at 6 and 14 weeks postpartum compared with placebo (30% lower, P = .04; 46% lower, P = .01, respectively), but not after 14 weeks. Cervical HIV-1 RNA detection was similar between arms (P = .91).

Conclusions. Valacyclovir significantly decreased early breast milk and plasma HIV-1 RNA among women receiving PMTCT.

Clinical Trials Registration. NCT00530777.

Introduction

Humoral immune responses play a pivotal role in naturally acquired immunity to malaria. Understanding which humoral responses are impaired among individuals at higher risk for malaria may improve our understanding of malaria immune control and contribute to vaccine development.

Methods

We compared humoral responses with 483 Plasmodium falciparum antigens between adults in, Kisumu (high, year-long malaria transmission leading to partial immunity), and adults in Kisii (low, seasonal malaria transmission). Then within each site, we compared malaria-specific humoral responses between those at higher risk for malaria (CD4+ ≤ 500) and those at lower risk for malaria (CD4+>500). A protein microarray chip containing 483 P. falciparum antigens and 71 HIV antigens was used. Benjamini–Hochberg adjustments were made to control for multiple comparisons.

Results

Fifty-seven antigens including CSP, MSP1, LSA1 and AMA1 were identified as significantly more reactive in Kisumu than in Kisii. Ten of these antigens had been identified as protective in an earlier study. CD4+ T-cell count did not significantly impact humoral responses.

Conclusion

Protein microarrays are a useful method to screen multiple humoral responses simultaneously. This study provides useful clues for potential vaccine candidates. Modest decreases in CD4 counts may not significantly impact malaria-specific humoral immunity.

Background. Although evidence supports a relationship between human immunodeficiency virus (HIV)–1 exposure and HIV-1−specific CD8+ T cell responses, studies have not demonstrated a direct association between the quantity of HIV-1 to which a person is exposed and the presence or absence of a response.

Methods. From 1999 to 2005, maternal HIV-1 RNA levels were measured in blood, cervical secretions, and breast milk at delivery and 1 month after delivery. HIV-1−specific interferon (IFN)–γ Elispot assays were conducted to determine infant CD8+ T-cell responses at 3 months of age.

Results. Among 161 infants tested with Elispot assays, 23 (14%) had positive results. Mothers whose infants had a positive assay had higher breast milk HIV-1 RNA levels at month 1 compared with mothers whose infants had negative Elispot assays (3.1 vs 2.5 log10 copies/mL; P = .017). Female infants were also more likely to have positive Elispot assays than male infants (P = .046), and in multivariate analyses, both female sex and high breast milk HIV-1 levels remained important predictors of a positive response (P = .022 and P = .015, respectively).

Conclusions. Exposure to breast milk HIV-1 and sex were associated with development of HIV-1−specific CD8+ T-cell responses in infants. These data support a role for mucosal exposure via the oral route in induction of systemic HIV-1−specific cellular immunity.

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV co-infected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly-active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg(+) and anti-HBs negative: 24 were HBeAg-negative, 18 had HBV DNA ≤10,000 IU/ml. Sustained HBV suppression to <100 IU/ml occurred in 89% of 19 evaluable patients. Resistance occurred in only 2 subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV co-infected patients with low baseline HBV DNA levels.

We examined associations between maternal HLA and vertical HIV-1 transmission in a perinatal cohort of 277 HIV-infected women in Nairobi. HLA class I genes were amplified using sequence-specific oligonucleotide probes and analyses were performed using logistic regression. Maternal A*2301 was associated with increased transmission risk before and after adjusting for maternal viral load (odds ratio [OR]=3.21; 95% CI: 1.42, 7.27, p=0.005, pcorr=0.04; adjusted OR=3.07; 95% CI: 1.26, 7.51, p=0.01, pcorr=NS). That maternal HLA-A*2301 was associated with transmission independent of plasma HIV-1 RNA levels, suggests that HLA may alter infectivity through mechanisms other than influencing HIV-1 viral load.

The relation between awareness of sexual partner’s HIV serostatus and unprotected sex was examined in HIV clinic enrollees. Increased condom use was associated with knowing that a partner was HIV-negative (adjusted odds ratio = 5.99; P < 0.001) versus not knowing partner’s status. Partner testing may increase condom use in discordant couples.

Background

There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression.

Methods

HIV-1–seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers.

Results

Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1–related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/µL/month (P< .001), HIV-1 RNA levels increased 0.005 log10 copies/mL/month (P = .03), and body mass index (BMI) decreased 0.03 kg/m2/month (P< .001). The rate of CD4 cell count decline was higher in breast-feeding mothers (7.2 cells/µL/month) than in mothers who never breast-fed (4.0 cells/µL/month) (P = .01). BMI decreased more rapidly in breast-feeding women (P = .04), whereas HIV-1 RNA levels and mortality did not differ significantly between breast-feeding and formula-feeding women.

Conclusions

Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.

Objective

To compare compliance and infant HIV-1 infection risk at 6 weeks with the Thai-CDC and HIVNET-012 antiretroviral regimens in a field setting.

Design

Randomized clinical trial.

Setting

Tertiary hospital antenatal clinic in Nairobi, Kenya.

Participants

HIV-1 infected women referred from primary care clinics.

Interventions

Thai-CDC zidovudine regimen or HIVNET-012 nevirapine regimen.

Main outcome measures

Women were considered compliant if they used ≥ 80% of the doses. Infants were tested for HIV-1 at 6 weeks.

Results

Seventy women were randomized to Thai-CDC and 69 to HIVNET-012 regimens. More women were compliant with the antenatal (86%) than the intrapartum (44%) Thai-CDC regimen doses (P = 0.001). Ninety-seven per cent took the maternal and 91% gave the infant dose of the HIVNET-012 regimen (P = 0.2). Overall, 41% were compliant with the Thai-CDC regimen and 87% with the HIVNET-012 regimen (P < 0.001). Compliance with the Thai-CDC regimen was associated with partner support of antiretroviral use [odds ratio (OR), 3.0;, 95% confidence interval (CI), 1.0–9.1] and knowledge at recruitment that antiretroviral drugs could prevent infant HIV-1 (OR, 2.9; 95% CI, 1.0–8.1). Compliance with the HIVNET-012 regimen was associated with partner notification (OR, 8.0; 95% CI, 1.5–50) and partner willingness to have HIV-1 testing (OR, 7.5; 95% CI, 1.4–40). There was a trend for a higher risk of transmission with the HIVNET-012 regimen than with the Thai-CDC regimen (22% versus 9%; P = 0.07).

Conclusion

Compliance with the Thai-CDC and HIVNET-012 regimens was comparable to that in efficacy trials. Partner involvement, support and education on perinatal HIV-1 prevention may improve compliance and increase the number of infants protected from HIV-1 infection.

Objectives

The objectives of this study were to determine patterns of contraceptive utilization among sexually active HIV-1-seropositive women postpartum and to identify correlates of hormonal contraception uptake.

Goal

The goal of this study was to improve delivery of family planning services to HIV-1-infected women in resource-limited settings.

Study Design

HIV-1-infected pregnant women were followed prospectively in a perinatal HIV-1 transmission study. Participants were referred to local clinics for contraceptive counseling and management.

Results

Among 319 HIV-1-infected women, median time to sexual activity postpartum was 2 months and 231 (72%) women used hormonal contraception for at least 2 months during follow-up, initiating use at approximately 3 months postpartum (range, 1–11 months). Overall, 101 (44%) used DMPA, 71 (31%) oral contraception, and 59 (25%) switched methods during follow-up. Partner notification, infant mortality, and condom use were similar between those using and not using contraception.

Conclusions

Using existing the healthcare infrastructure, it is possible to achieve high levels of postpartum hormonal contraceptive utilization among HIV-1-seropositive women.

The prevalence of human immunodeficiency virus (HIV)–1–infected cells and HIV-1 RNA levels in genital secretions and breast milk and the risk of mother-to-child transmission of HIV-1 were compared among subtypes A, C, and D in a Kenyan cohort. Pregnant women infected with subtype C were significantly more likely to shed HIV-1-infected vaginal cells than were those infected with subtype A or D (odds ratio [OR], 3.6 [95% confidence interval {CI}, 1.4–8.8]; P = .006). This relationship held after adjusting for age, CD4 cell count, and plasma HIV-1 RNA load (OR, 3.1 [95% CI, 1.1–8.6]; P = .03). These observations suggest that HIV-1 subtype influences mucosal shedding of HIV-1.

SUMMARY

In sub-Saharan Africa, over 22 million people are estimated to be co-infected with both helminths and HIV-1. Several studies have suggested that de-worming individuals with HIV-1 may delay HIV-1 disease progression, and that the benefit of de-worming may vary by individual helminth species. We conducted a systematic review and meta-analysis of the published literature to determine the effect of treatment of individual helminth infections on markers of HIV-1 progression (CD4 count and HIV viral load). There was a trend towards an association between treatment for Schistosoma mansoni and a decrease in HIV viral load (Weighted mean difference (WMD)=−0·10; 95% Confidence interval (CI): −0·24, 0·03), although this association was not seen for Ascaris lumbricoides, hookworm or Trichuris trichiura. Treatment of A. lumbricoides, S. mansoni, hookworm or T. trichiura was not associated with a change in CD4 count. While pooled data from randomized trials suggested clinical benefit of de-worming for individual helminth species, these effects decreased when observational data were included in the pooled analysis. While further trials are needed to confirm the role of anthelmintic treatment in HIV-1 co-infected individuals, providing anthelmintics to individuals with HIV-1 may be a safe, inexpensive and practical intervention to slow progression of HIV-1.

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 ≤ .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.

Summary

To determine effect of partner involvement and couple counseling on uptake of interventions to prevent HIV-1 transmission, women attending a Nairobi antenatal clinic were encouraged to return with partners for voluntary HIV-1 counseling and testing (VCT) and offered individual or couple posttest counseling. Nevirapine was provided to HIV-1-seropositive women and condoms distributed to all participants. Among 2104 women accepting testing, 308 (15%) had partners participate in VCT, of whom 116 (38%) were couple counseled. Thirty-two (10%) of 314 HIV-1-seropositive women came with partners for VCT; these women were 3-fold more likely to return for nevirapine (P = 0.02) and to report administering nevirapine at delivery (P = 0.009). Nevirapine use was reported by 88% of HIV-infected women who were couple counseled, 67% whose partners came but were not couple counseled, and 45% whose partners did not present for VCT (P for trend = 0.006). HIV-1-seropositive women receiving couple counseling were 5-fold more likely to avoid breast-feeding (P = 0.03) compared with those counseled individually. Partner notification of HIV-1-positive results was reported by 138 women (64%) and was associated with 4-fold greater likelihood of condom use (P = 0.004). Partner participation in VCT and couple counseling increased uptake of nevirapine and formula feeding. Antenatal couple counseling may be a useful strategy to promote HIV-1 prevention interventions.

Understanding how the level of human immunodeficiency virus type 1 (HIV-1)–infected breast milk cells (BMCs) affects HIV transmission via breast-feeding can shed light on the mechanism of infection and aid in establishing effective interventions. The proportion of infected cells to total cells was measured in serial breast milk samples collected from 291 HIV-1–infected women in Nairobi, Kenya, by use of real-time DNA polymerase chain reaction amplification of BMCs. The number of infected BMCs per million cells was associated with levels of cell-free viral RNA in breast milk (R = .144; P = .032), levels of cell-free virus in blood plasma (R = .365; P < .001), and the detection of proviral DNA in cervical and vaginal secretions (P < .001 and P = .030, respectively). The number of infected BMCs per million cells was lower in colostrum or early milk than in mature milk (P < .001). Previous studies demonstrated that the concentration of BMCs varies throughout lactation, and we used these data to transform infected BMCs per million cells to infected BMCs per milliliter. The estimated concentration of infected BMCs per milliliter was higher in colostrum or early milk than in mature milk (P < .001). Each log10 increase in infected BMCs per milliliter was associated with a 3.19-fold–increased risk of transmission (P = 002), after adjustment for cell-free virus in plasma (hazard ratio [HR], 2.09; P = 03) and breast milk (HR, 1.01; P = 1.00). This suggests that infected BMCs may play a more important role in transmission of HIV via breast-feeding than does cell-free virus.

Objectives

To determine the prevalence of life-time domestic violence by the current partner before HIV-1 testing, its impact on the uptake of prevention of mother-to-child transmission (PMTCT) interventions and frequency after testing.

Design

A prospective cohort.

Methods

Antenatally, women and their partners were interviewed regarding physical, financial, and psychological abuse by the male partner before HIV-1 testing and 2 weeks after receiving results.

Results

Before testing, 804 of 2836 women (28%) reported previous domestic violence, which tended to be associated with increased odds of HIV-1 infection [univariate odds ratio (OR) 1.7, 95% confidence interval (CI) 1.3–2.2; P < 0.0001, adjusted OR 1.2, 95% CI 0.9–1.6; P = 0.1], decreased odds of coming with partners for counseling (adjusted OR 0.7, 95% CI 0.5–1.0; P = 0.04), and decreased odds of partner notification (adjusted OR 0.7, 95% CI 0.5–1.1; P = 0.09). Previous domestic violence was not associated with a reduced uptake of HIV-1 counseling, HIV-1 testing, or nevirapine. After receiving results, 15 out of 1638 women (0.9%) reported domestic violence. After notifying partners of results, the odds of HIV-1-seropositive women reporting domestic violence were 4.8 times those of HIV-1-seronegative women (95% CI 1.4–16; P = 0.01). Compared with women, men reported similar or more male-perpetrated domestic violence, suggesting a cultural acceptability of violence.

Conclusion

Domestic violence before testing may limit partner involvement in PMTCT. Although infrequent, immediate post-test domestic violence is more common among HIV-1-infected than uninfected women. Domestic violence prevention programmes need to be integrated into PMTCT, particularly for HIV-1-seropositive women.

Objective

To determine whether implementation of free cotrimoxazole (CTX) provision was associated with improved retention among clients ineligible for antiretroviral therapy (ART) enrolled in an HIV treatment program in Kenya.

Design

Data were obtained from a clinical cohort for program evaluation purposes. Twelve-month clinic retention was compared among ART-ineligible clients enrolled in the time period before free CTX versus the time period after.

Methods

Statistical comparisons were made using Kaplan–Meier survival curves, log-rank tests, and multivariate Cox proportional hazards models. To exclude potential temporal program changes that may have influenced retention, ART clients before and after the same cut-off date were compared.

Findings

Among adult clients enrolled between 2005 and 2007, 3234 began ART within 1 year of enrollment, and 1024 of those who did not start treatment were defined as ART-ineligible. ART-ineligible clients enrolled in the period following free CTX provision had higher 12-month retention (84%) than those who enrolled prior to free CTX (63%; P < 0.001). Retention did not change significantly during these periods among ART clients (P = 0.55). In multivariate analysis, ART-ineligible clients enrolled prior to free CTX were more than twice as likely to be lost to follow-up compared to those following free CTX [adjusted hazard ratio (aHR) = 2.64, 95% confidence interval 1.95–3.57, P < 0.001].

Conclusion

Provision of free CTX was associated with significantly improved retention among ART-ineligible clients. Retention and CD4-monitoring of ART-ineligible clients are essential to promptly identify ART eligibility and provide treatment. Implementation of free CTX may improve retention in sub-Saharan Africa and, via increasing timely ART initiation, provide survival benefit.

Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and altered risk of mother-to-child HIV-1 transmission. To characterize CC and CXC chemokines in breastmilk postpartum, we collected breastmilk specimens at regular intervals for 6 months after delivery from women with and without HIV-1 infection and used commercial ELISA kits to measure breastmilk concentrations of MIP-1α, MIP-1β, RANTES, and SDF-1α. Among 54 HIV-1-infected and 26 uninfected women, mean chemokine levels were compared cross-sectionally and longitudinally at days 5 and 10, and months 1 and 3 postpartum. For both HIV-1-infected and uninfected women, breastmilk chemokine levels were highest at day 5 for MIP-1α, MIP-1β, and SDF-1α, and subsequently decreased. RANTES levels remained constant over the follow-up period among HIV-1-uninfected women, and increased moderately among HIV-1-infected women. For MIP-1β and RANTES, breastmilk levels were significantly higher among HIV-1-infected women compared to uninfected women early postpartum. In addition, HIV-1-infected women transmitting HIV-1 to their infant had consistently higher breastmilk RANTES levels than those who did not transmit, with the greatest difference observed at 1 month (2.68 vs. 2.21 log10 pg/mL, respectively; p = 0.007). In summary, all four chemokines were most elevated within the first month postpartum, a period of high transmission risk via breastmilk. MIP-1β and RANTES levels in breastmilk were higher among HIV-1-infected women than among uninfected women, and breastmilk RANTES was positively associated with vertical transmission in this study, consistent with results from our earlier cohort.

Secretory leukocyte protease inhibitor (SLPI), a protein found in saliva, breast milk, and genital secretions, is capable of inhibiting human immunodeficiency virus (HIV) type 1 in vitro. The aim of this study was to determine whether SLPI in infant saliva provides protection against mother-to-child HIV-1 transmission. In total, 602 saliva specimens were collected from 188 infants at birth and at ages 1, 3, and 6 months. Infants’ median salivary SLPI concentrations were higher at birth than at 6 months (341 vs. 219 ng/mL; P = .001). There was no association between SLPI concentration and HIV-1 transmission overall. However, among 122 breast-fed infants who were HIV-1 uninfected at 1 month, higher salivary SLPI levels were associated with a decreased risk of HIV-1 transmission through breast milk (hazard ratio, 0.5; 95% confidence interval, 0.3–0.9; P = .03). These results suggest that SLPI plays an important role in reducing HIV-1 transmission through breast milk.

Background

Studies among HIV-1–infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population.

Methods

To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1–infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1–specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer.

Results

Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks’ gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1–specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001).

Conclusions

This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1–exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1–exposed infants.

Vaccination of infants against human immunodeficiency virus type 1 (HIV-1) may prevent mother-to-child HIV-1 transmission. Successful trials and immunization efforts will depend on the willingness of individuals to participate in pediatric vaccine research and acceptance of infant HIV-1 vaccines. In a cross-sectional study, pregnant women presenting to a Nairobi antenatal clinic for routine care were interviewed regarding their attitudes toward participation in research studies and HIV-1 vaccine acceptability for their infants. Among 805 women, 782 (97%) reported they would vaccinate their infant against HIV-1 and 729 (91%) reported willingness to enroll their infant in a research study. However, only 644 (80%) would enroll their infants if HIV-1 testing was required every 3 months and 513 (64%) would agree to HIV-1 vaccine trial participation. Reasons for not wanting to enroll in a pediatric HIV-1 vaccine trial included concerns about side effects (75%), partner objection (34%), and fear of discrimination (10%), HIV-1 acquisition (8%), or false-positive HIV-1 results (5%). The strongest correlate of pediatric vaccine trial participation was maternal willingness to be a vaccine trial participant herself; in univariate and multivariate models this was associated with a 17-fold increased likelihood of participation (HR 17.1; 95% CI 11.7–25; p < 0.001). We conclude from these results that immunizing infants against HIV-1 and participation in pediatric vaccine trials are generally acceptable to women at high risk for HIV-1 infection. It will be important to address barriers identified in this study and to include male partners when mobilizing communities for pediatric HIV-1 vaccine trials and immunization programs.

Recombinant modified vaccinia virus Ankara expressing HIV-1 antigens (MVA.HIVA) was used in ELISpot assays to monitor HIV-1-specific T cell responses in infants. Responses to MVA.HIVA and HIV-1 peptides were examined in 13 infected and 81 exposed uninfected infants in Nairobi, Kenya. Responses to MVA.HIVA (38%) and peptide stimulation (38%) were similar in frequency (p = 1.0) and magnitude (mean 176 versus 385 HIVSFU/106, p = 0.96) in HIV-1 infected infants. In exposed uninfected infants, MVA.HIVA detected more positive responses and higher magnitude responses as compared to peptide. MVA.HIVA ELISpot is a sensitive method for quantification of HIV-1-specific CD8+ T cell responses in HIV-1 exposed infants. These results demonstrate the relevance of HIV-1 clade A consensus-derived immunogen HIVA for the viruses currently circulating in Nairobi.

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.

Human immunodeficiency virus type 1 (HIV-1) is transmitted through blood, genital secretions, and breast milk. The probability of heterosexual transmission of HIV-1 per sex act is .0003–0015, but little is known regarding the risk of transmission per breast-milk exposure. We evaluated the probability of breast-milk transmission of HIV-1 per liter of breast milk ingested and per day of breast-feeding in a study of children born to HIV-1–infected mothers. The probability of breast-milk transmission of HIV-1 was .00064 per liter ingested and .00028 per day of breast-feeding. Breast-milk infectivity was significantly higher for mothers with more-advanced disease, as measured by prenatal HIV-1 RNA plasma levels and CD4 cell counts. The probability of HIV-1 infection per liter of breast milk ingested by an infant is similar in magnitude to the probability of heterosexual transmission of HIV-1 per unprotected sex act in adults.

α-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 α-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 α-defensins, HIV-1 RNA, subclinical mastitis, and CC and CXC chemokines. We detected α-defensins in breast milk specimens from 108 (42%) of 260 HIV-1-infected women. Women with detectable α-defensins (≥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 α-defensins (2.9 log10 copies/ml versus 2.5 log10 copies/ml, p = 0.003). Increased α-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 α-defensins and risk of HIV-1 transmission. In conclusion, α-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 α-defensins and mother-to-child transmission, suggesting a complex interplay between breast milk HIV-1, inflammation, and antiinfective factors.