Impact of elevated maternal HIV viral load at delivery on T-cell populations in HIV exposed uninfected infants in Mozambique

Background: HIV-uninfected infants born to HIV-infected mothers (HIV-exposed uninfected, HEU) have been described to have immune alterations as compared to unexposed infants. This study sought to characterize T-cell populations after birth in HEU infants and unexposed infants living in a semirural area in southern Mozambique. Methods: Between August 2008 and June 2009 mother-infant pairs were enrolled at the Manhiça District Hospital at delivery into a prospective observational analysis of immunological and health outcomes in HEU infants. Infants were invited to return at one month of age for a clinical examination, HIV DNA-PCR, and immunophenotypic analyses. The primary analysis sought to assess immunological differences between HEU and unexposed groups, whereas the secondary analysis assessed the impact of maternal HIV RNA viral load in the HEU group. Infants who had a positive HIV DNA-PCR test were not included in the analysis. Results: At one month of age, the 74 HEU and the 56 unexposed infants had similar median levels of naïve, memory and activated CD8 and CD4 T-cells. Infant naïve and activated CD8 T-cells were found to be associated with maternal HIV-RNA load at delivery. HEU infants born to women with HIV-RNA loads above 5 log10 copies/mL had lower median levels of naïve CD8 T-cells (p = 0.04), and higher median levels of memory CD8 T-cells, (p = 0.014). Conclusions: This study suggests that exposure to elevated maternal HIV-RNA puts the infant at higher risk of having early T-cell abnormalities. Improving prophylaxis of mother to child HIV programs such that more women have undetectable viral load is crucial to decrease vertical transmission of HIV, but may also be important to reduce the consequences of HIV virus exposure in HEU infants

Recent HIV-1 Infection: Identification of Individuals with High Viral Load Setpoint in a Voluntary Counselling and Testing Centre in Rural Mozambique

Background: Identification of recent HIV-infections is important for describing the HIV epidemic and compiling HIV-RNA-setpoint data for future HIV intervention trials. We conducted a study to characterize recent infections, and HIV-RNA-setpoint within the adult population presenting at a voluntary counselling and testing centre (VCT) in southern Mozambique. Methods: All adults attending the Manhiça District-Hospital VCT between April and October 2009 were recruited if they had at least one positive rapid HIV-serology test. Patients were screened for recent HIV-1 infection by BED-CEIA HIV-incidence test. Clinical examination, assessment of HIV-RNA and CD4 cell counts were performed at enrollment, 4 and 10 months. Results: Of the 492 participants included in this study, the prevalence of recent infections as defined by BED-CEIA test, CD4 counts >200 cells/µl and HIV-RNA >400 copies/mL, was 11.58% (57/492; 95% CI 8.89-14.74). Due to heterogeneity in HIV-RNA levels in recently infected patients, individuals were categorized as having "high" HIV-RNA load if their HIV-RNA level was above the median (4.98 log10 copies/mL) at diagnosis. The "high" HIV-RNA group sustained a significantly higher HIV-viral load at all visits with a median HIV-RNA setpoint of 5.22 log10 copies/mL (IQR 5.18-5.47) as compared to the median of 4.15 log10 copies/ml (IQR 3.37-4.43) for the other patients (p = 0.0001). Conclusion: The low proportion of recent HIV-infections among HIV-seropositive VCT clients suggests that most of this population attends the VCT at later stages of HIV/AIDS. Characterization of HIV-RNA-setpoint may serve to identify recently infected individuals maintaining HIV viral load>5 log10 copies/mL as candidates for antiretroviral treatment as prevention interventions

Impact of elevated maternal HIV viral load at delivery on T-cell populations in HIV exposed uninfected infants in Mozambique

Background: HIV-uninfected infants born to HIV-infected mothers (HIV-exposed uninfected, HEU) have been described to have immune alterations as compared to unexposed infants. This study sought to characterize T-cell populations after birth in HEU infants and unexposed infants living in a semirural area in southern Mozambique. Methods: Between August 2008 and June 2009 mother-infant pairs were enrolled at the Manhiça District Hospital at delivery into a prospective observational analysis of immunological and health outcomes in HEU infants. Infants were invited to return at one month of age for a clinical examination, HIV DNA-PCR, and immunophenotypic analyses. The primary analysis sought to assess immunological differences between HEU and unexposed groups, whereas the secondary analysis assessed the impact of maternal HIV RNA viral load in the HEU group. Infants who had a positive HIV DNA-PCR test were not included in the analysis. Results: At one month of age, the 74 HEU and the 56 unexposed infants had similar median levels of naïve, memory and activated CD8 and CD4 T-cells. Infant naïve and activated CD8 T-cells were found to be associated with maternal HIV-RNA load at delivery. HEU infants born to women with HIV-RNA loads above 5 log10 copies/mL had lower median levels of naïve CD8 T-cells (p = 0.04), and higher median levels of memory CD8 T-cells, (p = 0.014). Conclusions: This study suggests that exposure to elevated maternal HIV-RNA puts the infant at higher risk of having early T-cell abnormalities. Improving prophylaxis of mother to child HIV programs such that more women have undetectable viral load is crucial to decrease vertical transmission of HIV, but may also be important to reduce the consequences of HIV virus exposure in HEU infants

Recent HIV-1 Infection: Identification of Individuals with High Viral Load Setpoint in a Voluntary Counselling and Testing Centre in Rural Mozambique

Background: Identification of recent HIV-infections is important for describing the HIV epidemic and compiling HIV-RNAsetpoint data for future HIV intervention trials. We conducted a study to characterize recent infections, and HIV-RNAsetpoint within the adult population presenting at a voluntary counselling and testing centre (VCT) in southern Mozambique. Methods: All adults attending the Manhiça District-Hospital VCT between April and October 2009 were recruited if they had at least one positive rapid HIV-serology test. Patients were screened for recent HIV-1 infection by BED-CEIA HIV-incidence test. Clinical examination, assessment of HIV-RNA and CD4 cell counts were performed at enrollment, 4 and 10 months. Results: Of the 492 participants included in this study, the prevalence of recent infections as defined by BED-CEIA test, CD4 counts.200 cells/ml and HIV-RNA.400 copies/mL, was 11.58 % (57/492; 95 % CI 8.89–14.74). Due to heterogeneity in HIV-RNA levels in recently infected patients, individuals were categorized as having ‘‘high’ ’ HIV-RNA load if their HIV-RNA level was above the median (4.98 log10 copies/mL) at diagnosis. The ‘‘high’ ’ HIV-RNA group sustained a significantly higher HIVviral load at all visits with a median HIV-RNA setpoint of 5.22 log10 copies/mL (IQR 5.18–5.47) as compared to the median of 4.15 log 10 copies/ml (IQR 3.37–4.43) for the other patients (p = 0.0001). Conclusion: The low proportion of recent HIV-infections among HIV-seropositive VCT clients suggests that most of thi

Evolution of median HIV-RNA load and CD4∶CD8 ratios in recently infected patients.

<p>HIV-RNA load (A) and CD4∶CD8 ratios (B) in patients with high HIV-RNA as compared to the other patients. Median and interquartile range are shown. HIV-RNA viral load groups are defined as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031859#s2" target="_blank">methods</a>. P-values are from Wilcoxon rank sum test between groups as follows: *p = 0.0001, **p = 0.038, *** p = 0.002. P-values from Wilcoxon Signed Rank between visits did not show significant differences. Numbers denote the n for each group at each time point.</p

Baseline virological and immunological parameters among individuals diagnosed with recent HIV infections by the BED-CEIA assay.

<p>Results are presented according to CD4 counts.</p><p>*CD4 counts available for 52/57 patients.</p

HIV serological characteristics of the study population (N = 492).

<p>RT: rapid testing. BED-CEIA: BED capture enzyme immunoassay. VL: Viral Load.</p><p>HIV positive and indeterminate serology by RT and BED-CEIA recent infection as defined in methods.</p

Self-reported clinical symptoms according to status of HIV infection.

<p>*Recent HIV infection defined by BED-CEIA, CD4 counts >200 cell/µl and VL>400 copies/mL.</p