Virological monitoring of HIV-infected patients on antiretroviral treatment (ART) is rarely avail... more Virological monitoring of HIV-infected patients on antiretroviral treatment (ART) is rarely available in resource-limited settings and many patients experience unrecognized virological failure. We studied the long-term consequences of virological failure in rural Tanzania. Previously, virological efficacy was measured in a cohort treated with ART. In the present study, patients with virological failure (VF; HIV-RNA >400 copies/ml) were followed up and compared to those with virological response (VR; HIV-RNA <400 copies/ml) with regard to mortality, CD4 change and subsequent virological outcome. Fifty-six patients with VF had a median CD4 count of 358 cells/µl (interquartile range (IQR) 223-635) and a median HIV-RNA of 13,573 copies/ml (IQR 2326-129,736). Median CD4 count for those with VR was 499 cells/µl (IQR 290-636). During a median follow-up time of 39 months (IQR 18-42), 8 of 56 patients (14.3%) with VF died, compared to 1 of 63 patients (1.6%) with VR (p = 0.009). All re...
Tuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapi... more Tuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapid TB diagnosis and ensure treatment initiation and cure are needed, especially in regions with high prevalence of multi-drug resistant TB. Soluble interferon gamma inducible protein 10 (IP-10) analyzed from dry plasma spots (DPS) has potential as an immunodiagnostic marker in TB infection. We analyzed IP-10 levels in plasma directly and extracted from DPS in parallel by ELISA from 34 clinically well characterized patients with TB disease before and throughout 24 weeks of effective anti-TB chemotherapy. We detected a significant decline of IP-10 levels in both plasma and DPS already after two weeks of therapy with good correlation between the tests. This was observed both in pulmonary and extrapulmonary TB. In conclusion, plasma IP-10 may serve as an early biomarker for anti-TB chemotherapy responses and the IP-10 DPS method has potential to be developed into a point-of care test for use ...
BackgroundInterferon-¿ release assays (IGRA) serve as immunodiagnostics of tuberculosis (TB) infe... more BackgroundInterferon-¿ release assays (IGRA) serve as immunodiagnostics of tuberculosis (TB) infection to identify individuals with latent TB infection (LTBI) eligible for preventive anti-TB therapy. In this longitudinal study of HIV-infected LTBI patients we have observed for possible progression to active TB as well as evaluated repeated IGRA testing in a TB low-endemic setting.MethodsQuantiFERON TB-Gold In-tube® assay (QFT), TB-SPOT.TB® (TSPOT) and tuberculin skin test (TST) were performed on 298 HIV-patients recruited from seven out-patient clinics in Norway. Patients with active TB, LTBI and negative IGRA were followed with repeat QFTs and clinical evaluation over a period of 24 months.ResultsSeven HIV-patients (median CD4 count 270; IQR 50¿340) were diagnosed with active TB at inclusion, all IGRA positive. Sixty-four (21%) HIV-patients (median CD4 count 471; IQR 342¿638) were diagnosed with LTBI and of these 39 (61%) received TB preventive treatment. Neither treated nor untrea...
Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. I... more Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. In the present study we have phenotyped apoptotic T cells in tonsillar lymphoid tissue from 11 HIV-1-infected patients by flow cytometry light-scatter characteristics during 48 weeks of highly active antiretroviral therapy (HAART). We found that the decline in tonsillar viral load was associated with a
Tuberculosis (TB) presents globally a significant health problem and health care workers (HCW) ar... more Tuberculosis (TB) presents globally a significant health problem and health care workers (HCW) are at increased risk of contracting TB infection. There is no diagnostic gold standard for latent TB infection (LTBI), but both blood based interferon-gamma release assays (IGRA) and the tuberculin skin test (TST) are used. According to the national guidelines, HCW who have been exposed for TB should be screened and offered preventive anti-TB chemotherapy, but the role of IGRA in HCW screening is still unclear. A total of 387 HCW working in clinical and laboratory departments in three major hospitals in the Western region of Norway with possible exposure to TB were included in a cross-sectional study. The HCW were asked for risk factors for TB and tested with TST and the QuantiFERON®TB Gold In-Tube test (QFT). A logistic regression model analyzed the associations between risk factors for TB and positive QFT or TST. A total of 13 (3.4%) demonstrated a persistent positive QFT, whereas 214 (55.3%) had a positive TST (≥ 6 mm) and 53 (13.7%) a TST ≥ 15 mm. Only ten (4.7%) of the HCW with a positive TST were QFT positive. Origin from a TB-endemic country was the only risk factor associated with a positive QFT (OR 14.13, 95% CI 1.37 - 145.38, p=0.026), whereas there was no significant association between risk factors for TB and TST ≥ 15 mm. The five HCW with an initial positive QFT that retested negative all had low interferon-gamma (IFN-γ) responses below 0.70 IU/ml when first tested. We demonstrate a low prevalence of LTBI in HCW working in hospitals with TB patients in our region. The &amp;amp;amp;amp;quot;IGRA-only&amp;amp;amp;amp;quot; seems like a desirable screening strategy despite its limitations in serial testing, due to the high numbers of discordant TST positive/IGRA negative results in HCW, probably caused by BCG vaccination or boosting due to repetitive TST testing. Thus, guidelines for TB screening in HCW should be updated in order to secure accurate diagnosis of LTBI and offer proper treatment and follow-up.
HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the r... more HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the residual viral load, repetitive blood and tonsillar samples were collected from 11 HIV-1-positive individuals before and during 96 weeks of therapy with zidovudine, lamivudine, and indinavir. HIV-1 RNA in tonsils was quantified by RT-PCR and infectious HIV-1 provirus by the limiting dilution assay. Genotypic resistance analyses and biological characterization were performed on plasma virus, blood, and tonsillar isolates. Tonsillar infectious HIV-1 provirus and HIV-1 RNA declined by 2 and 3 log(10), respectively, but 10(3)-10(4) cells, less than 0.5% of the total body CD4(+) T cell population carrying infectious HIV-1 provirus, remained involved in active viral replication of drug-sensitive R5 viruses. Thus, the dominant HIV-1 residual infection consists of &amp;amp;amp;amp;lt; or = 10(6) latently infected CD4(+) cells. Plasma HIV-1 RNA decline of &amp;amp;amp;amp;gt; 1.5 log(10) during the first 2 weeks of therapy may indicate low levels of this latent reservoir. Whereas the reservoir of latently infected cells remains stable, actively replicating HIV-1 continuously declines during prolonged antiretroviral therapy. Thus, although viral eradication seems unlikely, antiretroviral therapy may induce an extended period of virologic latency in HIV-1-positive individuals.
Virological monitoring of HIV-infected patients on antiretroviral treatment (ART) is rarely avail... more Virological monitoring of HIV-infected patients on antiretroviral treatment (ART) is rarely available in resource-limited settings and many patients experience unrecognized virological failure. We studied the long-term consequences of virological failure in rural Tanzania. Previously, virological efficacy was measured in a cohort treated with ART. In the present study, patients with virological failure (VF; HIV-RNA >400 copies/ml) were followed up and compared to those with virological response (VR; HIV-RNA <400 copies/ml) with regard to mortality, CD4 change and subsequent virological outcome. Fifty-six patients with VF had a median CD4 count of 358 cells/µl (interquartile range (IQR) 223-635) and a median HIV-RNA of 13,573 copies/ml (IQR 2326-129,736). Median CD4 count for those with VR was 499 cells/µl (IQR 290-636). During a median follow-up time of 39 months (IQR 18-42), 8 of 56 patients (14.3%) with VF died, compared to 1 of 63 patients (1.6%) with VR (p = 0.009). All re...
Tuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapi... more Tuberculosis (TB) has huge impact on human morbidity and mortality and biomarkers to support rapid TB diagnosis and ensure treatment initiation and cure are needed, especially in regions with high prevalence of multi-drug resistant TB. Soluble interferon gamma inducible protein 10 (IP-10) analyzed from dry plasma spots (DPS) has potential as an immunodiagnostic marker in TB infection. We analyzed IP-10 levels in plasma directly and extracted from DPS in parallel by ELISA from 34 clinically well characterized patients with TB disease before and throughout 24 weeks of effective anti-TB chemotherapy. We detected a significant decline of IP-10 levels in both plasma and DPS already after two weeks of therapy with good correlation between the tests. This was observed both in pulmonary and extrapulmonary TB. In conclusion, plasma IP-10 may serve as an early biomarker for anti-TB chemotherapy responses and the IP-10 DPS method has potential to be developed into a point-of care test for use ...
BackgroundInterferon-¿ release assays (IGRA) serve as immunodiagnostics of tuberculosis (TB) infe... more BackgroundInterferon-¿ release assays (IGRA) serve as immunodiagnostics of tuberculosis (TB) infection to identify individuals with latent TB infection (LTBI) eligible for preventive anti-TB therapy. In this longitudinal study of HIV-infected LTBI patients we have observed for possible progression to active TB as well as evaluated repeated IGRA testing in a TB low-endemic setting.MethodsQuantiFERON TB-Gold In-tube® assay (QFT), TB-SPOT.TB® (TSPOT) and tuberculin skin test (TST) were performed on 298 HIV-patients recruited from seven out-patient clinics in Norway. Patients with active TB, LTBI and negative IGRA were followed with repeat QFTs and clinical evaluation over a period of 24 months.ResultsSeven HIV-patients (median CD4 count 270; IQR 50¿340) were diagnosed with active TB at inclusion, all IGRA positive. Sixty-four (21%) HIV-patients (median CD4 count 471; IQR 342¿638) were diagnosed with LTBI and of these 39 (61%) received TB preventive treatment. Neither treated nor untrea...
Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. I... more Apoptosis has been proposed as a mechanism responsible for T cell depletion in HIV-1 infection. In the present study we have phenotyped apoptotic T cells in tonsillar lymphoid tissue from 11 HIV-1-infected patients by flow cytometry light-scatter characteristics during 48 weeks of highly active antiretroviral therapy (HAART). We found that the decline in tonsillar viral load was associated with a
Tuberculosis (TB) presents globally a significant health problem and health care workers (HCW) ar... more Tuberculosis (TB) presents globally a significant health problem and health care workers (HCW) are at increased risk of contracting TB infection. There is no diagnostic gold standard for latent TB infection (LTBI), but both blood based interferon-gamma release assays (IGRA) and the tuberculin skin test (TST) are used. According to the national guidelines, HCW who have been exposed for TB should be screened and offered preventive anti-TB chemotherapy, but the role of IGRA in HCW screening is still unclear. A total of 387 HCW working in clinical and laboratory departments in three major hospitals in the Western region of Norway with possible exposure to TB were included in a cross-sectional study. The HCW were asked for risk factors for TB and tested with TST and the QuantiFERON®TB Gold In-Tube test (QFT). A logistic regression model analyzed the associations between risk factors for TB and positive QFT or TST. A total of 13 (3.4%) demonstrated a persistent positive QFT, whereas 214 (55.3%) had a positive TST (≥ 6 mm) and 53 (13.7%) a TST ≥ 15 mm. Only ten (4.7%) of the HCW with a positive TST were QFT positive. Origin from a TB-endemic country was the only risk factor associated with a positive QFT (OR 14.13, 95% CI 1.37 - 145.38, p=0.026), whereas there was no significant association between risk factors for TB and TST ≥ 15 mm. The five HCW with an initial positive QFT that retested negative all had low interferon-gamma (IFN-γ) responses below 0.70 IU/ml when first tested. We demonstrate a low prevalence of LTBI in HCW working in hospitals with TB patients in our region. The &amp;amp;amp;amp;quot;IGRA-only&amp;amp;amp;amp;quot; seems like a desirable screening strategy despite its limitations in serial testing, due to the high numbers of discordant TST positive/IGRA negative results in HCW, probably caused by BCG vaccination or boosting due to repetitive TST testing. Thus, guidelines for TB screening in HCW should be updated in order to secure accurate diagnosis of LTBI and offer proper treatment and follow-up.
HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the r... more HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the residual viral load, repetitive blood and tonsillar samples were collected from 11 HIV-1-positive individuals before and during 96 weeks of therapy with zidovudine, lamivudine, and indinavir. HIV-1 RNA in tonsils was quantified by RT-PCR and infectious HIV-1 provirus by the limiting dilution assay. Genotypic resistance analyses and biological characterization were performed on plasma virus, blood, and tonsillar isolates. Tonsillar infectious HIV-1 provirus and HIV-1 RNA declined by 2 and 3 log(10), respectively, but 10(3)-10(4) cells, less than 0.5% of the total body CD4(+) T cell population carrying infectious HIV-1 provirus, remained involved in active viral replication of drug-sensitive R5 viruses. Thus, the dominant HIV-1 residual infection consists of &amp;amp;amp;amp;lt; or = 10(6) latently infected CD4(+) cells. Plasma HIV-1 RNA decline of &amp;amp;amp;amp;gt; 1.5 log(10) during the first 2 weeks of therapy may indicate low levels of this latent reservoir. Whereas the reservoir of latently infected cells remains stable, actively replicating HIV-1 continuously declines during prolonged antiretroviral therapy. Thus, although viral eradication seems unlikely, antiretroviral therapy may induce an extended period of virologic latency in HIV-1-positive individuals.
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Papers by Anne Dyrhol-Riise