Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Médecins Sans Frontières Experience in Guinea-Bissau and South Sudan.

Background: More than half of childhood tuberculosis cases remain undiagnosed yearly. The World Health Organization recommends the Xpert-Ultra assay as a first pediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra with stool and urine samples in presumptive pediatric tuberculosis cases in 2 high-tuberculosis-burden settings. Methods: This Médecins Sans Frontières cross-sectional multicentric study took place at Simão Mendes Hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal Hospital, South Sudan (April 2021 to June 2023). Children aged 6 months to 15 years with presumptive tuberculosis underwent clinical and laboratory assessment, with 1 respiratory and/or extrapulmonary sample (reference standard [RS]), 1 stool, and 1 urine specimen analyzed with Xpert-Ultra. Results: A total of 563 children were enrolled in the study, 133 from Bissau and 400 from Malakal; 30 were excluded. Confirmation of tuberculosis was achieved in 75 (14.1%), while 248 (46.5%) had unconfirmed tuberculosis. Of 553 with an RS specimen, the overall diagnostic yield was 12.4% (66 of 533). A total of 493 stool and 524 urine samples were used to evaluate the performance of Xpert-Ultra with these samples. Compared with the RS, the sensitivity and specificity of Xpert-Ultra were 62.5% (95% confidence interval, 49.4%-74%) and 98.3% (96.7%-99.2%), respectively, with stool samples, and 13.9% (7.5%-24.3%) and 99.4% (98.1%-99.8%) with urine samples. Nine patients were positive with stool and/or urine samples but negative with the RS. Conclusions: Xpert-Ultra in stool samples showed moderate to high sensitivity and high specificity compared with the RS and an added diagnostic yield when RS results were negative. Xpert-Ultra in stool samples was useful in extrapulmonary cases. Xpert-Ultra in urine samples showed low test performance. Clinical Trials Registration: NCT06239337.

Monocyte phenotype and extracellular vesicles in HIV-1, HIV-2, and HIV-1/2 dual infection.

OBJECTIVE: AIDS-defining illness develops at higher CD4 + T-cell counts in individuals infected with HIV-2 compared with HIV-1-infected, which suggests that the two types of HIV may have different effects on other compartments of the immune system. We here investigate monocyte phenotype, activation and macrophage-derived extracellular vesicles in individuals with different HIV types. DESIGN: Cross-sectional. METHODS: ART-naive HIV-1 ( n  = 83), HIV-2 ( n  = 63), and HIV-1/2 dually positive ( n  = 27) participants were recruited in Bissau, Guinea-Bissau, together with HIV-negative controls ( n  = 26). Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed by flow cytometry for monocyte phenotype and activation, and plasma was analyzed for extracellular vesicle forms of CD163 and CD206. RESULTS: Compared with HIV-negative controls, all groups of HIV-positive participants had a skewed monocyte phenotype with a higher proportion of intermediate monocytes, increased CD163 expression and elevated serum levels of the inflammatory biomarkers soluble (s)CD163 and sCD206. HIV-2-positive participants had lower CD163 monocyte expression than HIV-1-positive participants, regardless of HIV RNA or CD4 + cell count. Levels of sCD206 extracellular vesicles were increased in all HIV groups, and higher in HIV-1 compared with HIV-2-positive participants. CONCLUSION: The monocyte phenotype of HIV-2-positive participants deviated less from healthy controls than did HIV-1 participants. HIV-2-positive participants also had a lower concentration of extracellular CD206 vesicles compared with HIV-1-positive participants. This does not explain the difference in AIDS development.

Point-of-care ultrasound for tuberculosis diagnosis in children: a Médecins Sans Frontières cross-sectional study in Guinea-Bissau.

OBJECTIVE: Description of tuberculosis (TB)-focused point-of-care ultrasound (POCUS) findings for children with presumptive TB. DESIGN: Cross-sectional study (July 2019 to April 2020). SETTING: Simão Mendes hospital in Bissau, a setting with high TB, HIV, and malnutrition burdens. PARTICIPANTS: Patients aged between 6 months and 15 years with presumptive TB. INTERVENTIONS: Participants underwent clinical, laboratory and unblinded clinician-performed POCUS assessments, to assess subpleural nodules (SUNs), lung consolidation, pleural and pericardial effusion, abdominal lymphadenopathy, focal splenic and hepatic lesions and ascites. Presence of any sign prompted a POCUS positive result. Ultrasound images and clips were evaluated by expert reviewers and, in case of discordance, by a second reviewer. Children were categorised as confirmed TB (microbiological diagnosis), unconfirmed TB (clinical diagnosis) or unlikely TB. Ultrasound findings were analysed per TB category and risk factor: HIV co-infection, malnutrition and age. RESULTS: A total of 139 children were enrolled, with 62 (45%) women and 55 (40%) aged <5 years; 83 (60%) and 59 (42%) were severely malnourished (SAM) and HIV-infected, respectively. TB confirmation occurred in 27 (19%); 62 (45%) had unconfirmed TB and 50 (36%) had unlikely TB. Children with TB were more likely to have POCUS-positive results (93%) compared with children with unlikely TB (34%). Common POCUS signs in patients with TB were: lung consolidation (57%), SUNs (55%) and pleural effusion (30%), and focal splenic lesions (28%). In children with confirmed TB, POCUS sensitivity was 85% (95% CI) (67.5% to 94.1%). In those with unlikely TB, specificity was 66% (95% CI 52.2% to 77.6%). Unlike HIV infection and age, SAM was associated with a higher POCUS-positivity. Cohen's kappa coefficient for concordance between field and expert reviewers ranged from 0.6 to 0.9. CONCLUSIONS: We found a high prevalence of POCUS signs in children with TB compared with children with unlikely TB. POCUS-positivity was dependent on nutritional status but not on HIV status or age. TB-focused POCUS could potentially play a supportive role in the diagnosis of TB in children. TRIAL REGISTRATION NUMBER: NCT05364593.

The HIV care continuum of Guinea-Bissau; Progress towards the UNAIDS 90-90-90 targets for HIV-1 and HIV-2.

OBJECTIVE: In the 2020 UNAIDS HIV treatment goals, 90% of people living with HIV (PLHIV) should be diagnosed, 90% of these should receive antiretroviral treatment (ART) and 90% of these should be virally suppressed. We aimed to evaluate whether Guinea-Bissau fulfills the 2020 treatment goals for both for HIV-1 and HIV-2. DESIGN: By combining data from a general population survey, treatment records from HIV clinics across Guinea-Bissau and a biobank from patients attending the largest HIV clinics in Bissau, we estimated each column of the 90-90-90 cascade. METHOD: 2601 participated in the survey and were used to estimate the proportion of PLHIV who knew their HIV status and the proportion of PLHIV on ART. Answers given in the survey was verified with treatment records from HIV clinics. We measured viral load from biobank materials from HIV patients and estimated the proportion of virally suppressed PLHIV. RESULT: 19.1% of PLHIV indicated to be aware of their HIV status. Of these, 48.5% received ART, and 76.4% of these were virally suppressed. For HIV-1 and HIV-1/2 the results were 21.2%, 40.9% and 75.1%. For HIV-2 the results were 15.9%, 63.6% and 80.7%. 26.9% of all HIV-1 infected in the survey were virologically suppressed, indicating that a much higher number of HIV-1 infected were aware of their status and on treatment. CONCLUSION: Guinea-Bissau lags severely behind both the global and regional progress. Improvement in both testing and treating HIV is necessary to improve the quality of care.

Xpert MTB/RIF on urine samples to increase diagnosis of TB in people living with HIV in Guinea-Bissau.

OBJECTIVES: We investigated if Xpert MTB/RIF (Xpert) testing on urine samples among newly diagnosed HIV-patients as an adjunctive test to Xpert testing on sputum increases diagnosis. We sought to define subgroups of patients, for whom testing with either test is especially advantageous. METHODS: We included patients >15 years, newly diagnosed with HIV, that delivered a urine sample on the day of HIV-diagnosis at the biggest HIV-clinic in Guinea-Bissau between September 5, 2016 and October 13, 2017 into a cross-sectional study. Patients were asked for a sputum sample, which was Xpert tested if returned within 30 days. A questionnaire and physical examination were completed on day of inclusion. RESULTS: We included 390 patients. TB prevalence was 12.6%. Adding Xpert urine test to all newly diagnosed HIV-patients increased diagnostic yield of TB by 58% compared with testing on sputum alone. Patients who tested positive by Xpert on urine samples were clinically similar to those tested with sputum, except that the sputum positives reported more cough (p=0.03). CONCLUSIONS: Indiscriminate Xpert urine testing in newly diagnosed HIV-patients with advanced disease increased diagnostic yield. Xpert testing for TB on urine and sputum should be offered as screening in Guinea-Bissau and possibly in similar settings.

Life expectancy of HIV-infected patients followed at the largest hospital in Guinea-Bissau is one-fourth of life expectancy of the background population.

PURPOSE: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population. METHODS: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population. RESULTS: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed. CONCLUSIONS: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

A clinical score has utility in tuberculosis case-finding among patients with HIV: A feasibility study from Bissau.

BACKGROUND: Clinical scores are promising case-finding tools for tuberculosis (TB) among HIV-infected patients. The Bandim TBscore has been shown to increase the diagnostic yield among patients with presumed TB in general, but has not previously been tested among newly diagnosed HIV patients at high risk of TB. METHODS: HIV-infected patients were included in this cross-sectional study. A pre-post-intervention study design was used to assess the outcome of a change in practice, i.e. the application of a clinical score (TBscore) consisting of 13 signs and symptoms to assess the need for further TB diagnostics. Patients with a TBscore ≥2 were evaluated using smear microscopy and Xpert MTB/RIF. A TB diagnosis was made based on microbiology or clinical evaluation. The sensitivity and specificity of the TBscore were compared with those of World Health Organization symptoms. RESULTS: The TB prevalence among newly enrolled HIV-infected patients during the study period was 13.4% (22/164). Using the TBscore and a diagnostic algorithm, it was possible to increase the proportion of patients started on TB treatment from 2.7% (10/367) the year before the study to 10.4% (17/164) during the study period. Five patients diagnosed with TB were not started on TB treatment as they were lost to follow-up or died. With a cut-off value of 2, the TBscore had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.5% (21/22), 36.9% (41/111), 23.1% (22/118), and 97.6% (41/42), respectively. CONCLUSION: The TBscore is useful for standardized TB screening among HIV-infected individuals and may be a valuable tool to prioritize patients at high risk of TB.

Acceptance and Feasibility of Partner Notification to HIV Infected Individuals in Guinea-Bissau.

As partner notification (PN) has shown effective in increasing the number of partners of HIV infected patients being tested we aimed to evaluate the feasibility of implementing PN in the West-African country Guinea-Bissau. Patients enrolled were offered the choice of three different PN methods. Acceptance, successful referrals and HIV status of partners were evaluated. Of 697 patients offered PN, 495 (71.0%) accepted and listed 547 partners. At end of follow-up 118 (21.5%) partners had been tested of which 44 (37.3%) were HIV infected. HIV infected partners had a higher median CD4 count at diagnosis compared with index patients; 401 cells/mm3 versus 240 cells/mm3, p < 0.001. The results indicate that implementation of PN is feasible, effective in identifying HIV infected partners and enables initiation of earlier treatment, yet there are major barriers to bringing partners in for testing which should be addressed in order to exploit the full potential of PN.

HIV-2 as a model to identify a functional HIV cure.

Two HIV virus types exist: HIV-1 is pandemic and aggressive, whereas HIV-2 is confined mainly to West Africa and less pathogenic. Despite the fact that it has been almost 40 years since the discovery of AIDS, there is still no cure or vaccine against HIV. Consequently, the concepts of functional vaccines and cures that aim to limit HIV disease progression and spread by persistent control of viral replication without life-long treatment have been suggested as more feasible options to control the HIV pandemic. To identify virus-host mechanisms that could be targeted for functional cure development, researchers have focused on a small fraction of HIV-1 infected individuals that control their infection spontaneously, so-called elite controllers. However, these efforts have not been able to unravel the key mechanisms of the infection control. This is partly due to lack in statistical power since only 0.15% of HIV-1 infected individuals are natural elite controllers. The proportion of long-term viral control is larger in HIV-2 infection compared with HIV-1 infection. We therefore present the idea of using HIV-2 as a model for finding a functional cure against HIV. Understanding the key differences between HIV-1 and HIV-2 infections, and the cross-reactive effects in HIV-1/HIV-2 dual-infection could provide novel insights in developing functional HIV cures and vaccines.

Discriminatory rapid tests cause HIV-type misclassification-evaluation of three rapid tests using clinical samples from Guinea-Bissau.

BACKGROUND: Discrimination among HIV types is important because HIV-2 is naturally resistant to some of the first-line drugs used in the treatment of HIV-1. We evaluated three assays for HIV-type discriminatory capacity: SD Bioline HIV 1/2 3.0 (Bioline), First Response HIV 1-2-0 Card Test (First Response) and Genie III HIV-1/HIV-2 (Genie III). METHODS: Based on results from the Bioline assay, samples from 239 HIV-infected patients from the Bissau HIV cohort in Guinea-Bissau were retrospectively selected for evaluation. Genie III and First Response were scored by three independent readers and compared with a reference test (INNO-LIA HIV I/II Score) confirmed by HIV RNA as well as DNA detection. RESULTS: The best performing test was Genie III, with an average agreement with the reference test of 93.4%, followed by First Response (86.1%) and Bioline (72.4%). First Response and Bioline were scored with a false high number of HIV-1/2 dual infections. For both First Response and Genie III, there were discrepancies among independent readers, and some tests were scored as HIV non-reactive. CONCLUSIONS: Using these rapid tests with a suboptimal performance will presumably result in a high rate of false HIV-1/2 dual diagnoses, depriving patients of alternative treatment options in cases of treatment failure.

Performance of Bio-Rad HIV-1/2 Confirmatory Assay in HIV-1, HIV-2 and HIV-1/2 dually reactive patients - comparison with INNO-LIA and immunocomb discriminatory assays.

BACKGROUND: Being able to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection is imperative for the appropriate selection of antiretroviral therapy (ART) in regions with high HIV-2 endemicity. OBJECTIVES: To evaluate Bio-Rad Geenius HIV-1/2 Confirmatory Assay against INNO-LIA HIV 1/2 Score and ImmunoComb HIV 1/2 BiSpot with an emphasis towards ability to discriminate between HIV-1, HIV-2 and HIV-1/2 dual infection. MATERIAL AND METHODS: 131 samples from ART naïve HIV infected patients in Guinea-Bissau were selected retrospectively and tested with Geenius, INNO-LIA and Immunocomb. HIV-1/2 RNA were measured in all samples and HIV-1/2 DNA in 59 samples. RESULTS: The Geenius reader typed 62 samples as HIV-1 reactive, 37 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive. Geenius manual reading classified 10% more samples as HIV-1/2 dually reactive (n = 35). INNO-LIA typed 63 samples as HIV-1 reactive, 36 samples as HIV-2 reactive and 32 samples as HIV-1/2 dually reactive while Immunocomb classified a large proportion of samples as HIV-1/2 dually reactive (n = 45). The measurement of agreement of the Geenius reader compared with INNO-LIA and Immunocomb was 92.4% and 84.0% respectively while the measurement of agreement of Geenius manual reading compared with INNO-LIA and Immuncomb was 93.1% and 89.3% respectively. CONCLUSIONS: Geenius has similar performance characteristics as INNO-LIA, and performs considerably better than Immunocomb, for differentiating between HIV types. This is especially true when using the Geenius reader while manual reading of the Geenius assay seemed to overestimate the numbers of HIV-1/2 dually reactive samples.

T-cell and B-cell perturbations are similar in ART-naive HIV-1 and HIV-1/2 dually infected patients.

BACKGROUND: HIV-2 may slow progression of a subsequently acquired HIV-1 infection through cross-neutralizing antibodies and polyfunctional CD8 T cells. We hypothesized that HIV-1/2 dually infected patients compared with HIV-1-infected patients had more preserved immune maturation subsets and less immune activation of T and B cells. METHODS: ART-naive patients with HIV-1 (n = 83) or HIV-1/2 dual (n = 27) infections were included in this cross-sectional study at an HIV clinic in Guinea-Bissau. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry according to T-cell maturation and activation, regulatory T-cell fraction, and B-cell maturation and activation. RESULTS: HIV-1/2 dually infected patients had lower levels of HIV-1 RNA compared with patients with HIV-1 infection, but the levels of total HIV RNA (HIV-1 and HIV-2) were similar in the two patient groups. T-cell maturation, and proportions of regulatory T cells (FoxP3+) were also similar in the two groups. HIV-1/2 dually infected patients had higher proportions of CD4 and CD8 T cells positive for the activation marker CD38, but there was no difference in other T-cell activation markers (CD28, CTLA-4, PD-1). HIV-1/2 dually infected patients also had higher proportions of IgM-only B cells and plasmablasts. CONCLUSION: HIV-1/2 was not associated with less immune perturbations than for HIV-1 infection.

T-cell and B-cell perturbations identify distinct differences in HIV-2 compared with HIV-1-induced immunodeficiency.

BACKGROUND: For unknown reasons, HIV-2 is less pathogenic than HIV-1, and HIV-2-induced immunodeficiency may be different from that caused by HIV-1. Previous immunological studies have hinted at possible shifts in both T-cell and B-cell subsets, which we aimed to characterize further. METHODS: From an HIV clinic in Guinea-Bissau, 63 HIV-2, 83 HIV-1, and 26 HIV-negative participants were included. All HIV-infected participants were ART-naive. The following cell subsets were analysed by flow cytometry; T cells (maturation and activation), regulatory T cells, and B cells (maturation and activation). RESULTS: After standardizing for sex, age, and CD4 T-cell count HIV-2 had 0.938 log10 copies/ml lower HIV RNA levels than the HIV-1-infected patients. Whereas T-cell maturation and regulatory T-cell profiles were similar between patients, HIV-2-infected patients had higher proportions of CD8CD28 and lower proportions of CD8PD-1+ T cells than HIV-1-infected patients. This finding was independent of HIV RNA levels. HIV-2 was also associated with a more preserved proportion of naive B cells. CONCLUSION: HIV-2 is characterized by lower viral load, and lower T-cell activation, which may account for the slower disease progression.

HLA-DQB1*06:276, a novel HLA allele fund in a patient from Guinea-Bissau.

DQB1*06:276 differs from DQB1*06:03:01:01 by amino acid substitutions p.T71A, p.G74S, and p.L75V in exon 2.

Two novel HLA-B alleles, HLA-B*53:01:17 and -B*58:83, found in patients from Guinea-Bissau.

Novel HLA-B alleles HLA-B*53:01:17 and HLA-B*58:83 are described in two patients from Guinea-Bissau.

Excessive mortality and loss to follow-up among HIV-infected children in Guinea-Bissau, West Africa: a retrospective follow-up study.

OBJECTIVES: To estimate the magnitude of mortality and loss to follow-up and describe predictors of mortality among HIV-infected children in Guinea-Bissau. METHODS: Retrospective follow-up study among HIV-infected children under 15 years of age at the largest HIV-clinic in Guinea-Bissau from 2006-2016. A multivariate Cox proportional hazards model was used to identify predictors of mortality. RESULTS: Of 525 children were included in the analysis: 371 (70.7%) with HIV-1, 17 (3.2%) with HIV-2, 25 (4.8%) with HIV-1/2, and 112 (21.3%) with HIV of unknown type. At diagnosis, the median age was 3.5 years, 44.7% met the WHO criteria for severe immunodeficiency by age based on CD4 cell count, and 59.4% were underweight. The median follow-up time was 6 months. Despite the availability of antiretroviral treatment, the mortality rate was 10.4 deaths per 100 person-years of follow-up. Within the first year of follow-up, 11.0% died, 3.1% were transferred and 38.8% were lost to follow-up, leaving 47.1% in follow-up. Severe immunodeficiency (adjusted hazard ratio (aHR) = 2.52, 95% CI: 1.22-5.21) and underweight (aHR = 3.14, 95% CI: 1.40-7.02) were independent predictors of mortality. CONCLUSIONS: This study reveals a high rate of early mortality and loss to follow-up among HIV-infected children in Guinea-Bissau. Initiatives to improve patient retention are urgently needed.

Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial.

BACKGROUND: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are recommended as part of first-line treatment for HIV-1 in Africa. However, NNRTI-based regimens are more prone to resistance development than protease inhibitors (PIs) in a context in which drug interruptions are frequent. The aim of this study was to compare the efficacy and tolerability of NNRTIs with PIs in HIV-1-infected patients in Guinea-Bissau. METHODS: This open-label randomized, 2-arm superiority trial compared the use of 2 NRTIs plus either one NNRTI (efavirenz or nevirapine) or one PI (lopinavir/ritonavir) in treatment-naive HIV-1-infected adults in the Bissau HIV Cohort (ClinicalTrials.gov, NCT0019235). The primary endpoint was HIV-1 RNA <400 copies per milliliter after 12 months of treatment. RESULTS: Between May 5, 2011, and April 26, 2013, 400 patients were included in the study. In an intention-to-treat analysis, the proportions of patients with viral suppression were similar in the NNRTI [65/197 (33.0%)] and PI [68/203 (33.5%)] arms (P = 0.92). No PI resistance was detected, but high-level NNRTI resistance was seen in 17/30 (56.7%) of NNRTI vs. 3/26 (11.5%) of PI-treated patients, P < 0.01. After 1 year of follow-up, 65 patients died (16.3%) and 93 were lost to follow-up (23.3%). There was no difference in mortality (hazard ratio 0.84, 95% confidence interval: 0.51 to 1.36) or frequency of clinical adverse events between treatment arms [NNRTI: 73/197 (37.1%); and PI: 69/203 (34.0%); P = 0.52]. CONCLUSIONS: In patients at an HIV clinic in Guinea-Bissau, treatment with PIs led to less development of resistance compared with NNRTIs but was not superior in terms of viral suppression, CD4 cell increment, mortality, or severe adverse events.

Prevalence and clinical characteristics of CMV coinfection among HIV infected individuals in Guinea-Bissau: a cross-sectional study.

OBJECTIVES: To describe the prevalence of CMV in a cohort of HIV infected individuals in Guinea-Bissau, West Africa and to evaluate differences in patients' clinical characteristics associated with their CMV status. METHODS: Newly diagnosed HIV infected adults were invited to participate in this cross-sectional study, from May until December 2015. Enrolled patients were interviewed and underwent a full physical examination focusing on CMV disease manifestations. Blood samples were analysed for CMV serology, QuantiFERON-CMV response and CMV DNA. Mortality follow-up were registered for one year after inclusion. RESULTS: In total, 180 patients were enrolled. Anti-CMV IgG positivity was found in 100% (138/138) and 2.8% (4/138) were anti-CMV IgM positive. A positive QuantiFERON-CMV response was found in 85.7% (60/70) of the patients and 60.6% (83/137) had CMV viraemia. QuantiFERON-CMV response and detectable CMV DNA were associated with lower CD4 cell count, older age and upper gastrointestinal complaints. During one year of follow-up, the IRR for death among CMV DNA positive patients was 1.5 (P = 0.5). CONCLUSIONS: CMV coinfection was detected among all enrolled patients and CMV viraemia was highly prevalent. Only age and upper gastrointestinal complaints were associated with the patients' CMV status.

Soluble Macrophage Mannose Receptor (sCD206/sMR) as a Biomarker in Human Immunodeficiency Virus Infection.

Macrophages play important roles during human immunodeficiency virus (HIV) infection, reflected by changes in macrophage-activation biomarker soluble CD163 (sCD163). Here, we present data on the novel macrophage-activation biomarker soluble mannose receptor/CD206 (sCD206) in HIV infection. We investigated sCD206 blood levels at baseline and follow-up with/without antiretroviral therapy (ART), in 212 patients with HIV type 1 (HIV-1), HIV type 2 (HIV-2), or dual infection. At baseline, there was no difference in sCD206 level between HIV types, and sCD206 was unchanged at follow-up without ART. However, in contrast to sCD163, sCD206 levels decreased significantly for both HIV-1 and HIV-2, but not for HIV-1/2 patients, during ART. Further investigations are needed to establish sCD206 as a biomarker in HIV infection.