Non-recent Infection Research Articles

The impact of regional socioeconomic deprivation on the timing of HIV diagnosis: a cross-sectional study in Germany

BackgroundHIV infections which are diagnosed at advanced stages are associated with significantly poorer health outcomes. In Germany, the proportion of persons living with HIV who are diagnosed at later stages has remained continuously high. This study examined the impact of regional socioeconomic deprivation on the timing of HIV diagnosis.MethodsWe used data from the national statutory notification of newly diagnosed HIV infections between 2011 and 2018 with further information on the timing of diagnosis determined by the BED-Capture-ELISA test (BED-CEIA) and diagnosing physicians. Data on regional socioeconomic deprivation were derived from the German Index of Socioeconomic Deprivation (GISD). Outcome measures were a non-recent infection based on the BED-CEIA result or an infection at the stage of AIDS. The effect of socioeconomic deprivation on the timing of diagnosis was analysed using multivariable Poisson regression models with cluster-robust error variance.ResultsOverall, 67.5% (n = 10,810) of the persons were diagnosed with a non-recent infection and 15.2% (n = 2746) with AIDS. The proportions were higher among persons with heterosexual contact compared to men who have sex with men (MSM) (76.8% non-recent and 14.9% AIDS vs. 61.7% non-recent and 11.4% AIDS). MSM living in highly deprived regions in the countryside (< 100 k residents) were more likely to have a non-recent infection (aPR: 1.16, 95% CI: 1.05–1.28) as well as AIDS (aPR: 1.41, 95% CI: 1.08–1.85) at the time of diagnosis compared to MSM in less deprived regions in the countryside. No differences were observed among MSM from towns (100 k ≤ 1 million residents) or major cities (≥ 1 million residents), and no differences overall in the heterosexual transmission group.ConclusionsAn effect of socioeconomic deprivation on the timing of HIV diagnosis was found only in MSM from countryside regions. We suggest that efforts in promoting HIV awareness and regular HIV testing are increased for heterosexual persons irrespective of socioeconomic background, and for MSM with a focus on those living in deprived regions in the countryside.

Performance of a novel rapid test for recent HIV infection among newly-diagnosed pregnant adolescent girls and young women in four high-HIV-prevalence districts-Malawi, 2017-2018.

Tests for recent HIV infection (TRI) distinguish recent from long-term HIV infections using markers of antibody maturation. The limiting antigen avidity enzyme immunoassay (LAg EIA) is widely used with HIV viral load (VL) in a recent infection testing algorithm (RITA) to improve classification of recent infection status, estimate population-level HIV incidence, and monitor trends in HIV transmission. A novel rapid test for recent HIV infection (RTRI), Asanté™, can determine HIV serostatus and HIV recency within minutes on a lateral flow device through visual assessment of test strip or reader device. We conducted a field-based laboratory evaluation of the RTRI among pregnant adolescent girls and young women (AGYW) attending antenatal clinics (ANC) in Malawi.We enrolled pregnant AGYW aged <25 years testing HIV-positive for the first time at their first ANC visit from 121 ANCs in four high-HIV burden districts. Consenting participants provided blood for recency testing using LAg EIA and RTRI, which were tested in central laboratories. Specimens with LAg EIA normalized optical density values ≤2.0 were classified as probable recent infections. RTRI results were based on: (1) visual assessment: presence of a long-term line (LT) indicating non-recent infection and absence of the line indicating recent infection; or (2) a reader; specimens with LT line intensity units <3.0 were classified as probable recent infections. VL was measured for specimens classified as a probable recent infections by either assay; those with HIV-1 RNA ≥1,000 copies/mL were classified as confirmed recent infections. We evaluated the performance of the RTRI by calculating correlation between RTRI and LAg EIA results, and percent agreement and kappa between RTRI and LAg EIA RITA results.Between November 2017 to June 2018, 380 specimens were available for RTRI evaluation; 376 (98.9%) were confirmed HIV-positive on RTRI. Spearman's rho between RTRI and LAg EIA was 0.72 indicating strong correlation. Percent agreement and kappa between RTRI- and LAg EIA-based RITAs were >90% and >0.65 respectively indicating substantial agreement between the RITAs.This was the first field evaluation of an RTRI in sub-Saharan Africa, which demonstrated good performance of the assay and feasibility of integrating RTRI into routine HIV testing services for real-time surveillance of recent HIV infection.

Association between Continuous Flow Left Ventricular Assist Device Infections Requiring Long-Term Antibiotic Use and Post Heart Transplant Morbidity and Mortality

PurposeInfections in patients with a left ventricular assist device (LVAD) for bridge to heart transplant (HTx) do not appear to impact post-HTx survival. We evaluated the association between LVAD-related infections requiring long-term suppressive antibiotics and non-recent infections of any kind on the risk of early and late infection, rejection and mortality post-HTx in comparison to LVAD recipients without infection.MethodsThis is a single-center retrospective observational cohort study of consecutive adults with a durable continuous flow LVAD undergoing HTx between 2006-2019. Patients were grouped into: 1) LVAD-related infection requiring long-term antibiotic use until time of HTx; 2) any type of infection after LVAD implant in whom antibiotics were stopped at least 1 month prior to HTx; and 3) no infections between LVAD implant and HTx. LVAD-related infections included bacteremia, driveline or pocket. We evaluated the association between LVAD infection and post-HTx in-hospital infection, rejection and mortality using logistic regression, and long-term infection, rejection and mortality using Cox PH models.ResultsWe included 75 LVAD recipients; 16 (21%) patients had an LVAD-related infection on suppressive antibiotics, 30 (40%) had a non-recent infection, and 29 (39%) had no infections. During a median post-HTx follow-up time of 4 (2-7) years, we observed 65/75 (87%) infections, 43/67 (64%) rejections, and 17/75 (23%) deaths. Both short- and long-term risk of infection, rejection, and mortality did not differ significantly among the groups (Table 1).ConclusionLVAD patients with history of infections did not have higher risk of infection, rejection or mortality at any time point after HTx. Different post-HTx management strategies may have buffered the risk of adverse events in LVAD patients with infections. Infections in patients with a left ventricular assist device (LVAD) for bridge to heart transplant (HTx) do not appear to impact post-HTx survival. We evaluated the association between LVAD-related infections requiring long-term suppressive antibiotics and non-recent infections of any kind on the risk of early and late infection, rejection and mortality post-HTx in comparison to LVAD recipients without infection. This is a single-center retrospective observational cohort study of consecutive adults with a durable continuous flow LVAD undergoing HTx between 2006-2019. Patients were grouped into: 1) LVAD-related infection requiring long-term antibiotic use until time of HTx; 2) any type of infection after LVAD implant in whom antibiotics were stopped at least 1 month prior to HTx; and 3) no infections between LVAD implant and HTx. LVAD-related infections included bacteremia, driveline or pocket. We evaluated the association between LVAD infection and post-HTx in-hospital infection, rejection and mortality using logistic regression, and long-term infection, rejection and mortality using Cox PH models. We included 75 LVAD recipients; 16 (21%) patients had an LVAD-related infection on suppressive antibiotics, 30 (40%) had a non-recent infection, and 29 (39%) had no infections. During a median post-HTx follow-up time of 4 (2-7) years, we observed 65/75 (87%) infections, 43/67 (64%) rejections, and 17/75 (23%) deaths. Both short- and long-term risk of infection, rejection, and mortality did not differ significantly among the groups (Table 1). LVAD patients with history of infections did not have higher risk of infection, rejection or mortality at any time point after HTx. Different post-HTx management strategies may have buffered the risk of adverse events in LVAD patients with infections.

Structure of general-population antibody titer distributions to influenza A virus

Seroepidemiological studies aim to understand population-level exposure and immunity to infectious diseases. Their results are normally presented as binary outcomes describing the presence or absence of pathogen-specific antibody, despite the fact that many assays measure continuous quantities. A population’s natural distribution of antibody titers to an endemic infectious disease may include information on multiple serological states – naiveté, recent infection, non-recent infection, childhood infection – depending on the disease in question and the acquisition and waning patterns of immunity. In this study, we investigate 20,152 general-population serum samples from southern Vietnam collected between 2009 and 2013 from which we report antibody titers to the influenza virus HA1 protein using a continuous titer measurement from a protein microarray assay. We describe the distributions of antibody titers to subtypes 2009 H1N1 and H3N2. Using a model selection approach to fit mixture distributions, we show that 2009 H1N1 antibody titers fall into four titer subgroups and that H3N2 titers fall into three subgroups. For H1N1, our interpretation is that the two highest-titer subgroups correspond to recent and historical infection, which is consistent with 2009 pandemic attack rates. Similar interpretations are available for H3N2, but right-censoring of titers makes these interpretations difficult to validate.

Evaluation of the TGS TA system for the detection of anti-cytomegalovirus antibodies

&lt;em&gt;Background and aims:&lt;/em&gt; The aim of the present study was to evaluate the new Technogenetics TGS TA system for detecting anti-Cytomegalovirus IgG and IgM antibodies and IgG avidity. The TGS TA system was compared with our routinely used system, LIAISON XL, for the detection of IgG and IgM antibodies. Only in positive IgM samples, TGS TA system was compared to an enzyme linked fluorescent assay (ELFA) test (VIDAS, BioMérieux, Marcy-l’Étoile, France) and with LIAISON XL system for the IgG avidity (if possible). &lt;br /&gt;&lt;em&gt;Materials and methods:&lt;/em&gt; Three hundred sera samples from pregnant women were examined with the TGS TA system and divided in 3 groups according to IgG and IgM screening LIAISON XL tests: 102 were non-immune women (Group 1), 98 were pregnant with past infection (Group 2) and 100 were pregnant with positive or equivocal IgM (95 with positive IgG and 5 with negative IgG) (Group 3). &lt;br /&gt;&lt;em&gt;Results:&lt;/em&gt; The overall concordance of the IgG results between LIAISON XL and TGS TA was 98.3%: 97.1% in Group 1, 100% in Group 2 and 98.0% in Group 3. The overall concordance of the IgM results between LIAISON XL and TGS TA was 92.1%: 100% in Group 1, 99.0% in Group 2 and 70.1% in Group 3. In Group 3, the concordance between the results of the IgG avidity with the LIAISON XL and TGS TA tests was 87.4%. Comparing the clinical diagnosis obtained with our protocol and that of the TGS TA system, the overall concordance was 94.3%: 97.1% in Group 1, 99.0% in Group 2 and 87.0% in Group 3. &lt;br /&gt;&lt;em&gt;Conclusions&lt;/em&gt;: In conclusion, the overall clinical concordance between the LIAISON XL/VIDAS protocol and the TGS TA system is excellent. TGA TA system shows to be a valuable tool able to clearly identify non-specific subjects, those with a non-recent infection and classify as either recent or past infection half of the subjects with undetermined infection with our protocol.

Evaluation of the TGS TA system for the detection of anti-rubella antibodies

&lt;p&gt;&lt;em&gt;Background and aims:&lt;/em&gt; The aim of the present study was to evaluate the new Technogenetics TGS TA system for detecting antirubella IgG and IgM antibodies and IgG avidity. TGS TA system was compared with our routinely used system, LIAISON XL, for the detection of IgG and IgM antibodies. Only in positive IgM samples (retrospective study), TGS TA system was compared to an ELFA IgM test and with an ELISA test for the IgG avidity (if existent).&lt;br /&gt;&lt;em&gt;Materials and methods:&lt;/em&gt; Two hundred and seventy six sera samples from women were examined with TGS TA system and divided in 3 groups according to IgG and IgM screening LIAISON XL tests: 112 were of childbearing age and non-immune women (Group 1), 106 were pregnant with past infection or vaccinated (Group 2) and 49 were pregnant with positive or equivocal IgM (Group 3). &lt;br /&gt;&lt;em&gt;Results&lt;/em&gt;: The overall concordance of the IgG results between LIAISON XL and TGS TA was 93.3%: 86.6% in Group 1, 97.2% in Group 2 and 100% in Group 3. The overall concordance of the IgM results between LIAISON XL and TGS TA was 89.0%: 100% in Group 1, 100% in Group 2 and 35.6% in Group 3. In Group 3, the concordance between the results of the IgG avidity with the ELISA and TGS TA tests was 85.7%. Comparing the clinical diagnosis obtained with our protocol and that of the TGS TA system, the overall concordance was 97.4%: 86.6% in Group 1, 97.2% in Group 2 and 85.7% in Group 3. &lt;br /&gt;&lt;em&gt;Conclusions&lt;/em&gt;: TGA TS system shows to be a valuable tool with overall good clinical correlation and able to clearly identify nonspecific subjects, those with a non-recent infection or those who are vaccinated. The TGS TA test also seems to be especially sensitive in indicating vaccinated subjects with low IgG levels as immune.&lt;/p&gt;

Evaluation of the TGS TA system for the detection of anti-Toxoplasma antibodies

&lt;em&gt;Background and aims.&lt;/em&gt; The aim of the present study was to evaluate the new chemiluminescence TGS TA system of Technogenetics (Milan, Italy) for detecting anti-Toxoplasma IgG and IgM antibodies and IgG avidity. The TGS TA system was compared with our chemiluminescence routinely used system, LIAISON XL, supplied by Diasorin (Saluggia, Italy), for the detection of IgG and IgM antibodies. Only in positive IgM samples (retrospective study) and for the IgG avidity (if existent), TGS TA system was compared to an Enzyme Linked Fluorescent Assay (ELFA) test (VIDAS, BioMérieux, Marcy-l’Étoile, France). &lt;br /&gt;&lt;em&gt;Materials and methods&lt;/em&gt;. Three hundred and one sera samples, from women who came to our centre for the routine follow up pregnancy, were examined with the TGS TA system and divided in 3 groups according to IgG and IgM screening LIAISON XL tests: 106 were non-immune women (Group 1), 100 were pregnant with past infection (Group 2) and 95 were pregnant with positive or equivocal IgM (82 with positive IgG and 13 with negative IgG) (Group 3). &lt;br /&gt;&lt;em&gt;Results&lt;/em&gt;. The overall concordance of the IgG results between LIAISON XL and TGS TA was 99.3%: 100% in Group 1, 98% in Group 2 and 100% in Group 3. The overall concordance of the IgM results between LIAISON XL and TGS TA was 93.9%: 100% in Group 1, 94% in Group 2 and 82.8% in Group 3. In Group 3, the concordance between the results of the IgG avidity with the ELFA and TGS TA tests was 81.7%. Comparing the clinical diagnosis obtained with our protocol and that of the TGS TA system, the overall concordance was 92.7%: 100% in Group 1, 92.0% in Group 2 and 78.9% in Group 3. &lt;br /&gt;&lt;em&gt;Conclusions&lt;/em&gt;. The overall concordance of IgG antibodies is excellent for both protocols while for IgM antibodies is very high in the first group and lower in the third group, due to the presence of non-specific IgM subjects in this group. The TGS TA avidity test seems to predict ealier the maturation of the IgG compared to the ELFA test since many samples with low avidity with the ELFA were seen with moderate avidity with TGS TA and all those with borderline avidity with the ELFA were seen with high avidity with TGS TA. This system shows to be a valuable tool with overall good clinical correlation and able to clearly identify nonspecific subjects, those with a non-recent infection.

Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061).

BackgroundHIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.MethodsA high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits.ResultsMen with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment.ConclusionsHIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.

Ten Years Survey of Primary HIV-1 Resistance in Serbia: The Occurrence of Multiclass Resistance

In Serbia, the first cases of HIV infection were reported in 1985, whereas antiretroviral (ARV) therapy has been in use since 1987. With this study we aimed to assess the occurrence and pattern of HIV resistance mutations among newly diagnosed patients in the period 2002-2011. The study prospectively included 181 adult patients. Genotypic HIV-1 drug resistance testing was performed and drug resistance was scored according to the 2009 WHO list for surveillance of drug resistance mutations (SDRMs). A bioinformatic approach was used to estimate the duration of infection by calculating the percentage of ambiguous basecalls per sequence, with a cutoff of 0.47% as the delimiter for recent infection. The overall prevalence of transmitted drug resistance (TDR) found in the study was 8.8% (16/181, 95% CI=5.5-13.8). Thirty-one percent of resistant samples contained multiple SDRMs. In particular, 5/16 patients with resistance carried viral strains with SDRMs to multiple ARV classes, hence one-third of resistant strains were multiclass resistant, including non-B strains. A total of 51.9% of samples (94/181) were classified as recent infection, with a significant increase in the second part of the study period. However, the prevalence of TDR in recent infection was 6.4% (6/94, 95% CI=2.9-13.2), not statistically different from that found in nonrecent infection. We showed a changing pattern of TDR mutations over the study period, with a substantial occurrence of multiclass resistance, across different HIV subtypes. Our results highlight the need for continued surveillance of primary resistance.

Antibody Maturation and Viral Diversification in HIV-Infected Women

IntroductionThe Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women.MethodsSamples collected at enrollment (N = 2,561) and 12–24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67).ResultsIn PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.ConclusionsAntibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.

Augmented Cross‐Sectional Prevalence Testing for Estimating HIV Incidence

Estimation of an HIV incidence rate based on a cross-sectional sample of individuals evaluated with both a sensitive and less-sensitive diagnostic test offers important advantages to incidence estimation based on a longitudinal cohort study. However, the reliability of the cross-sectional approach has been called into question because of two major concerns. One is the difficulty in obtaining a reliable external approximation for the mean "window period" between detectability of HIV infection with the sensitive and less-sensitive test, which is used in the cross-sectional estimation procedure. The other is how to handle false negative results with the less-sensitive diagnostic test; that is, subjects who may test negative-implying a recent infection-long after they are infected. We propose and investigate an augmented design for cross-sectional incidence estimation studies in which subjects found in the recent infection state are followed for transition to the nonrecent infection state. Inference is based on likelihood methods that account for the length-biased nature of the window periods of subjects found in the recent infection state, and relate the distribution of their forward recurrence times to the population distribution of the window period. The approach performs well in simulation studies and eliminates the need for external approximations of the mean window period and, where applicable, the false negative rate.

Implications for HIV testing policy derived from combining data on voluntary confidential testing with viral sequences and serological analyses

Objectives:Laboratory, clinical and sequence-based data were combined to assess the differential uptake of voluntary confidential HIV testing (VCT) according to risk and explore the occurrence of HIV transmission from individuals...