P02-07. High Concentrations of Interleukin-15 and Low Concentrations of CCL5 in Breast Milk are Associated with Protection against Postnatal HIV Transmission

Background: Natural variations in IL-15 concentration have not been investigated for an association with an immune-protection against HIV. Given IL-15's central role in anti-HIV immunity, we hypothesized that higher concentrations of IL-15 in breast milk may protect against postnatal mother-to-child HIV transmission. Methods: In a case-control study nested within a clinical trial in Zambia, we compared IL-15 concentrations in breast milk of 22 HIV-infected women who transmitted HIV to their infants through breastfeeding with those of 72 who did not, as well as 18 HIV-uninfected women. Breast milk HIV RNA quantity, sodium, CXCL12, CCL5, and IL-8 concentrations were measured as well as maternal plasma HIV RNA concentrations and CD4 cell count. We used logistic regression modeling to adjust for potential confounders. Results: Higher concentrations of IL-15 in breast milk (adjusted odds ratio [AOR]: 0.01 per log10 pg/ml increase, 95% confidence interval [CI]: <0.001 to 0.3) were associated with protection against postnatal HIV transmission in univariate analysis and after adjusting for maternal CD4 cell counts, breast milk HIV RNA, CCL5, CXCL12, and IL-8 concentrations. Breast milk IL-15 concentration correlated with breast milk sodium, the other cytokines and HIV RNA concentration. It was inversely correlated with infant birth weight and tended to be higher in 1 week than in 1 month post-partum samples. Breast milk CCL5 concentrations were associated with increased risk of HIV transmission (AOR: 12.7 95% CI: 1.6 to 102.0) in adjusted analysis. Breast milk CXCL12 and IL-8 concentrations were not independently associated with transmission. Conclusion: High concentration of IL-15 were associated with a protection against breastfeeding HIV transmission after adjusting for other pro-inflammatory cytokines, HIV RNA in breast milk, and maternal CD4 cell count. These results corroborate a protective role of IL-15-mediated cellular immunity against HIV transmission during breastfeeding. They are informative for vaccination studies using IL-15 as an adjuvant

Prevalence of clinical, immunological and irological failure among children on Haart at the university teaching hospital, Lusaka, Zambia

Background: There is increasing evidence that the current clinical and immunological monitoring tools are not sufficient to identify early enough patients who are failing on treatment. Development of resistance to the limited treatment options for children and premature switching are the dangers. The objective of this study was to review patient records to see how well WHO staging, CD4 profiles and viral load estimations relate in children on treatment at the University Teaching Hospital (UTH).Methods: A retrospective chart review of all children aged between 0-19 years that started treatment between January 2004 and Dec 2010 was carried out at the UTH. Systematic sampling was done of every second child who received HAART for more than 24 weeks, with at least one viral load (VL) reading beyond 24 weeks of treatment. Six-monthly clinical (WHO staging) immunological (age- related CD4 count/%) and virological data were collected until last follow-up review or five years on treatment. The 2010 Zambian Pediatric Guidelines were used to gauge age-related clinical, immunological and virological failure (VL&gt; 1,000).Results: A total of 517 patient records were reviewed (table 1). Mean age at ART initiation was 7 years ((SD 4.7yrs). Mean time after ART initiation when first viral load test was done was 2.7 years (SD 1.5yrs). Of all the viral loads done, 64% (328) had a routine indication for patients on treatment nearing the 3 year mark (mean 2.7 years). In 40% of children the first viral load test result was above 1,000 after 24 weeks or more of treatment. A total of 482 patients had WHO staging done at the time first VL test was done. Of the 359 patients (table 2) with a clinical stage I/II (not severely immunosuppressed), 41% were failing virologically. On the other hand, 63% of the patients with clinical stage III/IV had a VL below 1,000. Table 3 shows that there were 509 patients who had an immunological staging done at the time first VL was done. Of the 106 patients who were failing immunologically, 28% were virologically well suppressed. On the other hand of the 403 who were immunologically doing fine, 32% were failing virologically.Conclusions: Clinical staging and Immunological monitoring in children on ART does not accurately identify those that are failing. A push for routine, affordable virological testing is needed to identify treatment failures early to prevent development of ART resistance and to avoid premature switches to second line in those who are actually well suppressed

Functional Properties of the HIV-1 Subtype C Envelope Glycoprotein Associated with Mother-to-Child Transmission

Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the newly transmitted variants were sensitive to neutralization by pooled heterologous plasma but in general were resistant to IgG1 b12. Neither Env processing nor incorporation efficiency was predictive of viral transmissibility. These findings provide further insight into the characteristics of perinatally transmissible HIV-1 and may have implications for intervention approaches

Healthy pregnancies and essential fats: focus group discussions with Zambian women on dietary need and acceptability of a novel RUSF containing fish oil DHA

Background: Nut butter-based Ready to Use Supplemental Foods (RUSF) are an effective way to add nutrients and calories to diets of malnourished and food insecure populations. The RUSF formulations have been further modified to add micronutrients including iron and folic acid needed during pregnancy and lactation. Because docosahexaenoic acid (DHA, C22:6 n-3) enhances fetal development and birth outcomes, it has been suggested that perhaps RUSF formulations for pregnancy should also include this Omega 3 fatty acid. The goal of the present study was to gain an understanding of Zambian women’s knowledge of nutritional needs in pregnancy through structured focus group discussions, and to formulate and determine the acceptability of a RUSF with DHA. Methods: Structured focus group sessions were conducted among women attending an antenatal clinic at the University Teaching Hospitals in Lusaka, Zambia. Dietary and nutrition knowledge was surveyed through structured dialogue that was recorded by audio and transcribed verbatim. An RUSF containing 400 mg DHA from fish oil in 50 g RUSF was designed and assessed for fatty acid content and product stability. Participants then sampled the RUSF- DHA, provided feedback on taste, and were surveyed about willingness to consume the novel formula using a standardized hedonic instrument. Results: The participants’ knowledge of foods recommended for use in pregnancy included fruits, vegetables, meat, and fish. Most women reported eating fish at least once per week, although the specific type of fish varied. Most did not have prior knowledge of the importance of consuming fish during pregnancy or that some fish types were more nutritional than others as they included omega 3 fatty acids. The participants were uniformly accepting of the RUSF-DHA for the purpose of enhancing birth and developmental outcomes, but were critical of the aroma in hedonic testing. Conclusions: Women were committed to consuming a healthy diet that would impact the outcome of pregnancy, and were receptive to advice on the importance of consuming foods such as fish as a source of DHA. The RUSF- DHA formulation was acceptable due to the potential benefits for the developing infant, however, the fishy odor may be limiting for long-term daily us

HIV Testing for Children in Resource-Limited Settings: What Are We Waiting For?

Scott Kellerman and Shaffiq Essajee argue that the time has come to increase access to HIV testing for children, especially in sub-Saharan Africa

Case Report Catheter-Related Acremonium kiliense Fungemia in a Patient with Ulcerative Colitis under Treatment with Infliximab

is properly cited. Acremonium spp. are filamentous, cosmopolitan fungi commonly isolated from plant debris and soil. They are infrequent pathogens in humans. Acremonium fungemia has been reported in neutropenic patients associated with central venous catheters and in nonneutropenic patients receiving long-term total parenteral nutrition. TNF-α blockade is associated with fungal infections, but no Acremonium spp. infection had been reported up to the present. In this paper, we present a patient with ulcerative colitis who developed Acremonium kiliense fungemia associated with infliximab therapy while receiving total parenteral nutrition. The patient was successfully treated with voriconazole. Acremonium sp. infection must be suspected as another cause of fungal infection in patients under treatment with infliximab

Institutionalizing Provider-Initiated HIV Testing and Counselling for Children: An Observational Case Study from Zambia

Background: Provider-initiated testing and counselling (PITC) is a priority strategy for increasing access for HIV-exposed children to prevention measures, and infected children to treatment and care interventions. This article examines efforts to scale-up paediatric PITC at a second-level hospital located in Zambia’s Southern Province, and serving a catchment area of 1.2 million people. Methods and Principal Findings: Our retrospective case study examined best practices and enabling factors for rapid institutionalization of PITC in Livingstone General Hospital. Methods included clinical observations, key informant interviews with programme management, and a desk review of hospital management information systems (HMIS) uptake data following the introduction of PITC. After PITC roll-out, the hospital experienced considerably higher testing uptake. In a 36-month period following PITC institutionalization, of total inpatient children eligible for PITC (n = 5074), 98.5 % of children were counselled, and 98.2 % were tested. Of children tested (n = 4983), 15.5 % were determined HIVinfected; 77.6 % of these results were determined by DNA polymerase chain reaction (PCR) testing in children under the age of 18 months. Of children identified as HIV-infected in the hospital’s inpatient and outpatient departments (n = 1342), 99.3 % were enrolled in HIV care, including initiation on co-trimoxazole prophylaxis. A number of good operational practices and enabling factors in the Livingstone General Hospital experience can inform rapid PIT

Restricted Genetic Diversity of HIV-1 Subtype C Envelope Glycoprotein from Perinatally Infected Zambian Infants

Background: Mother-to-child transmission of HIV-1 remains a significant problem in the resource-constrained settings where anti-retroviral therapy is still not widely available. Understanding the earliest events during HIV-1 transmission and characterizing the newly transmitted or founder virus is central to intervention efforts. In this study, we analyzed the viral env quasispecies of six mother-infant transmission pairs (MIPs) and characterized the genetic features of envelope glycoprotein that could influence HIV-1 subtype C perinatal transmission. Methodology and Findings: The V1-V5 region of env was amplified from 6 MIPs baseline samples and 334 DNA sequences in total were analyzed. A comparison of the viral population derived from the mother and infant revealed a severe genetic bottleneck occurring during perinatal transmission, which was characterized by low sequence diversity in the infant. Phylogenetic analysis indicates that most likely in all our infant subjects a single founder virus was responsible for establishing infection. Furthermore, the newly transmitted viruses from the infant had significantly fewer potential N-linked glycosylation sites in Env V1-V5 region and showed a propensity to encode shorter variable loops compared to the nontransmitted viruses. In addition, a similar intensity of selection was seen between mothers and infants with a higher rate of synonymous (dS) compared to nonsynonymous (dN) substitutions evident (dN/dS\u3c1). Conclusions: Our results indicate that a strong genetic bottleneck occurs during perinatal transmission of HIV-1 subtype C. This is evident through population diversity and phylogenetic patterns where a single viral variant appears to be responsible for infection in the infants. As a result the newly transmitted viruses are less diverse and harbored significantly less glycosylated envelope. This suggests that viruses with the restricted glycosylation in envelope glycoprotein appeared to be preferentially transmitted during HIV-1 subtype C perinatal transmission. In addition, our findings also indicated that purifying selection appears to predominate in shaping the early intrahost evolution of HIV-1 subtype C envelope sequences

Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania

<p>Abstract</p> <p>Background</p> <p>In Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation.</p> <p>Methods</p> <p>In September 2006, a molecular biology laboratory at Bugando Medical Center was established in order to perform HIV DNA PCR testing using Dried Blood Spots (DBS). Ninety- six health workers from 4 health facilities were trained in the identification and care of HIV-exposed infants, HIV testing algorithms and collection of DBS samples. Paper-based tracking systems for monitoring the program that fed into a simple electronic database were introduced at the sites and in the laboratory. Time from birth to first HIV DNA PCR testing and to receipt of test results were assessed using Kaplan-Meier curves.</p> <p>Results</p> <p>From October 2006 to March 2007, 510 HIV-exposed infants were identified from the 4 health facilities. Of these, 441(87%) infants had an HIV DNA PCR test at a median age of 4 months (IQR 1 to 8 months) and 75(17%) were PCR positive. Parents/guardians for a total of 242(55%) HIV-exposed infants returned to receive PCR test results, including 51/75 (68%) of those PCR positive, 187/361 (52%) of the PCR negative, and 4/5 (80%) of those with indeterminate PCR results. The median time between blood draw for PCR testing and receipt of test results by the parent or guardian was 5 weeks (range <1 week to 14 weeks) among children who tested PCR positive and 10 weeks (range <1 week to 21 weeks) for those that tested PCR negative.</p> <p>Conclusions</p> <p>The EID pilot program successfully introduced systems for identification of HIV-exposed infants. There was a high response as hundreds of HIV-exposed infants were registered and tested in a 6 month period. Challenges included the large proportion of parents not returning for PCR test results. Experience from the pilot phase has informed the national roll-out of the EID program currently underway in Tanzania.</p