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

Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa.

CAPRISA, 2015.Abstract available in pdf

IP-10 Levels as an Accurate Screening Tool to Detect Acute HIV Infection in Resource-Limited Settings.

Acute HIV infection (AHI) is the period prior to seroconversion characterized by high viral replication, hyper-transmission potential and commonly, non-specific febrile illness. AHI detection requires HIV-RNA viral load (VL) determination, which has very limited access in low-income countries due to restrictive costs and implementation constraints. We sought to identify a biomarker that could enable AHI diagnosis in scarce-resource settings, and to evaluate the feasibility of its implementation. HIV-seronegative adults presenting at the Manhiça District Hospital, Mozambique, with reported-fever were tested for VL. Plasma levels of 49 inflammatory biomarkers from AHI (n = 61) and non-HIV infected outpatients (n = 65) were determined by Luminex and ELISA. IP-10 demonstrated the best predictive power for AHI detection (AUC = 0.88 [95%CI 0.80-0.96]). A cut-off value of IP-10 ≥ 161.6 pg/mL provided a sensitivity of 95.5% (95%CI 85.5-99.5) and a specificity of 76.5% (95%CI 62.5-87.2). The implementation of an IP-10 screening test could avert from 21 to 84 new infections and save from US$176,609 to US$533,467 to the health system per 1,000 tested patients. We conclude that IP-10 is an accurate biomarker to screen febrile HIV-seronegative individuals for subsequent AHI diagnosis with VL. Such an algorithm is a cost-effective strategy to prevent disease progression and a substantial number of further HIV infections

Challenges of diagnosing acute HIV-1 subtype C infection in African women: performance of a clinical algorithm and the need for point-of-care nucleic-acid based testing.

Background. Prompt diagnosis of acute HIV infection (AHI) benefits the individual and provides opportunities for public health intervention. The aim of this study was to describe most common signs and symptoms of AHI, correlate these with early disease progression and develop a clinical algorithm to identify acute HIV cases in resource limited setting. Methods. 245 South African women at high-risk of HIV-1 were assessed for AHI and received monthly HIV-1 antibody and RNA testing. Signs and symptoms at first HIV-positive visit were compared to HIV-negative visits. Logistic regression identified clinical predictors of AHI. A model-based score was assigned to each predictor to create a risk score for every woman. Results. Twenty-eight women seroconverted after a total of 390 person-years of follow-up with an HIV incidence of 7.2/100 person-years (95%CI 4.5–9.8). Fifty-seven percent reported ≥1 sign or symptom at the AHI visit. Factors predictive of AHI included age <25 years (OR = 3.2; 1.4–7.1), rash (OR = 6.1; 2.4–15.4), sore throat (OR = 2.7; 1.0–7.6), weight loss (OR = 4.4; 1.5–13.4), genital ulcers (OR = 8.0; 1.6–39.5) and vaginal discharge (OR = 5.4; 1.6–18.4). A risk score of 2 correctly predicted AHI in 50.0% of cases. The number of signs and symptoms correlated with higher HIV-1 RNA at diagnosis (r = 0.63; p<0.001). Conclusions. Accurate recognition of signs and symptoms of AHI is critical for early diagnosis of HIV infection. Our algorithm may assist in risk-stratifying individuals for AHI, especially in resource-limited settings where there is no routine testing for AHI. Independent validation of the algorithm on another cohort is needed to assess its utility further. Point-of-care antigen or viral load technology is required, however, to detect asymptomatic, antibody negative cases enabling early interventions and prevention of transmission

Epidemiología de las fases tempranas de la infección por el VIH en pacientes ambulatorios de una zona semi-rural del sur de Mozambique

Las etapas iniciales de la infección por VIH se caracterizan por elevados niveles de ARN viral, que pueden estar contribuyendo significativamente a la transmisión del virus y al mantenimiento de la epidemia. Existe poca información sobre estas etapas precoces de la infección en zonas de África donde predomina el subtipo C del VIH. Este trabajo ha caracterizado la epidemiología y los parámetros inmuno-virológicos de las fases iniciales de la infección por VIH en una zona del sur de Mozambique La primera parte de este trabajo se enfocó en la identificación de infecciones agudas (AHI) en pacientes ambulatorios de una zona semi-rural del sur de Mozambique. En esta zona endémica de malaria, la población está habituada a acudir al hospital tras sentir síntomas febriles característicos de la malaria, pero también del síndrome retroviral agudo del VIH. Esta situación, presente en muchos países del sur de África, presenta una oportunidad de dirigir una búsqueda de casos de AHI hacia pacientes con síndrome febril. Usando esta estrategia, se describió una elevada prevalencia de AHI (3.3%) en los pacientes ambulatorios con síndrome febril. Estos pacientes mostraron elevados niveles de carga viral (CV) y de activación de las células T-CD8. En la segunda parte de este trabajo, se caracterizó la infección reciente por VIH, definida como los primeros 12 meses desde la infección. Se encontró una baja prevalencia de infecciones recientes por VIH (11.58%) en personas que acuden voluntariamente al centro de asesoramiento para VIH del hospital. Un grupo de pacientes identificados con infección reciente por VIH mostraron, como en el caso de los AHI, elevados niveles de carga viral por encima de 105 copias/ml de plasma que fueron mantenidos durante los 10 meses de seguimiento. Estos pacientes con elevados niveles de CV representarían un mayor riesgo de transmisión del VIH, señalando la importancia en la identificación de infecciones agudas y recientes para las estrategias de prevención del VIH. Los resultados de esta tesis reúnen información sobre la epidemiología de las fases iniciales de la infección por VIH en una zona de elevada prevalencia donde no había datos previos. Estos resultados contribuyen a la caracterización de las fases tempranas de la infección por VIH con la perspectiva de llevar a cabo intervenciones en las fases iniciales para mejorar el pronóstico del paciente y disminuir el riesgo de transmisión. Además apoyan la necesidad de más desarrollo de pruebas de diagnóstico rápido para la detección de las fases tempranas en condiciones locales

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