Early Diagnosis Of HIV Infection Research Articles

One-year frailty transitions among persons living with HIV aged 70 years or more on antiretroviral treatment

Abstract Background People living with HIV (PLWH) are aging. Frailty is an age-related condition predictive of hospitalization and mortality. Here, we assessed the frequency and factors associated with frailty transitions at one-year follow-up in elderly PLWH. Method 508 PLWH aged 70 years or older, on antiretroviral treatment, were included in the French multicenter SEPTAVIH study in 2019-2020. Participants were classified as robust, prefrail or frail according to Fried frailty phenotype, at baseline and at one year. Logistic regression models were used to evaluate socioeconomic or medical factors associated with transition between frailty states. Models were adjusted for gender, age at baseline, education, and period of HIV diagnosis (before versus after 1996). Results 17 PLWH died during the one-year follow-up. Of the remaining 491 PLWH, aged 73 years in median, frailty status worsened for 18% of participants and improved for 14% at one year. Advanced age, baseline CD4+ T-cell count below 350 cells/mm3 and type 2 diabetes were associated with transition from prefrailty to frailty: adjusted odds ratio (aOR) 1.10 per a one-year positive difference [95% confidence interval (CI): 1.01; 1.20], 3.05 [1.14; 8.18] and 2.63 [1.05; 6.57], respectively. Being female was associated with more frequent improvement from prefrailty to robustness, aOR 2.50 [1.09; 5.55]. Conclusions Preventing frailty in elderly PLWH is a long-term problem, beginning with the early diagnosis of HIV infection and the management of comorbidities.

Comparison of Two Molecular Tests, Roche COBAS<sup>®</sup>AmpliPrep/COBAS<sup>®</sup>TaqMan<sup>®</sup> and Abbott-RealTime in the HIV-1 Early Infants Diagnosis

<i>Background: </i>Prompt diagnosis and treatment of infants born to parents living with HIV is essential to reduce infant mortality. The availability of several high-throughput automated molecular tests is necessary to increase the services of early diagnosis tests in infants, especially in countries with limited resources such as Senegal. <i>Objective: </i>The objective of this study was to compare two automated molecular tests, Roche COBAS^®AmpliPrep/COBAS^® TaqMan^®HIV-1 Qualitative and Abbott RealTime HIV-1 Qualitative in the early diagnosis of HIV-1 infection in children born to HIV-positive mothers in Senegal. Methods: The study was conducted exclusively at the molecular biology laboratory of the armed forces AIDS programme at the Ouakam Military Hospital, Dakar, Senegal, between September 2020 and December 2021. It involved 136 children aged between 1 and 18 months born to HIV-1 infected mothers. The samples were taken from blood obtained from the baby's heel, dried on blotting paper (DBS) and sent to the molecular biology laboratory. They were then stored at room temperature before being tested for the study. After these samples were analysed on both molecular techniques, the Abbott Qualitative results were compared to diagnostic tests performed with Roche COBAS^®AmpliPrep/COBAS^®TaqMan^®HIV-1 Qualitative, which is the reference molecular technique. R Studio software version 099.902, 2016 was used to calculate specificity and sensitivity and Kappa coefficient. For statistical tests, they are considered significant when the P-value is less than 5%. <i>Results:</i> Out of a total of 136 samples tested, the overall positive and negative concordance was 94.84%, 79.41% and 93.58% respectively. The concordance coefficient, Cohen's Kappa coefficient, was also analysed. It gave a value of 0.853 (95% CI: [74.7-95.8]). A discrepancy was found between the two tests. Seven samples, which had previously tested positive on Roche Cobas, tested negative on Abbott Qualitative. <i>Conclusion: </i>The result showed a comparable performance characterized by very good negative, positive and global concordances and also, a very high Cohen's Kappa coefficient κ. The present study showed that the two molecular tests are comparable and that the Abbott Qualitative is a practical alternative for the diagnosis of HIV in infants.

Evaluation of antiretroviral therapy effect and prognosis between HIV-1 recent and long-term infection based on a rapid recent infection testing algorithm.

Early diagnosis of HIV-1 infection and immediate initiation of combination antiretroviral therapy (cART) are important for achieving better virological suppression and quicker immune reconstitution. However, no serological HIV-1 recency testing assay has been approved for clinical use, and the real-world clinical outcomes remain to be explored for the subjects with HIV-1 recent infection (RI) or long-term infection (LI) when antiretroviral therapy is initiated. In this study, a HIV-1 rapid recent-infection testing strip (RRITS) was developed and incorporated into the recent infection testing algorithms (RITAs) to distinguish HIV-1 RI and LI and to assess their clinical outcomes including virological response, the recovery of CD4+ T-cell count and CD4/CD8 ratio and the probability of survival. We found that the concordance between our RRITS and the commercially available LAg-Avidity EIA was 97.13% and 90.63% when detecting the longitudinal and cross-sectional HIV-1 positive samples, respectively. Among the 200 HIV-1 patients analyzed, 22.5% (45/200) of them were RI patients and 77.5% (155/200) were chronically infected and 30% (60/200) of them were AIDS patients. After cART, 4.1% (5/155) of the LI patients showed virological rebound, but none in the RI group. The proportion of CD4+ T-cell count >500 cells/mm3 was significantly higher in RI patients than in LI after 2 years of cART with a hazard ratio (HR) of 2.6 (95% CI: 1.9, 3.6, p < 0.0001) while the probability of CD4/CD8 = 1 was higher in RI than in LI group with a HR of 3.6 (95% CI: 2.2, 5.7, p < 0.0001). Furthermore, the immunological recovery speed was 16 cells/mm3/month for CD4+ T-cell and 0.043/month for the ratio of CD4/CD8 in the RI group, and was bigger in the RI group than in the LI patients (p < 0.05) during the 1st year of cART. The survival probability for LI patients was significantly lower than that for RI patients (p < 0.001). Our results indicated that RRITS combined with RITAs could successfully distinguish HIV-1 RI and LI patients whose clinical outcomes were significantly different after cART. The rapid HIV-1 recency test provides a feasible assay for diagnosing HIV-1 recent infection and a useful tool for predicting the outcomes of HIV-1 patients.

Low Prevalence of Transmitted HIV-1 Antiretroviral Resistance in Pregnant Women from Rio de Janeiro, Brazil

Background: HIV screening during antenatal care is being expanded in Brazil for early diagnosis of HIV-1 infection during pregnancy and prevention of vertical transmission. HIV genotyping in pregnant women is crucial to reduce the risk of vertical transmission in those carrying resistant strains and may also be used for Transmitted Drug Resistance (TDR) surveillance purpose. We evaluated prevalence and patterns of HIV-1 TDR and HIV subtype distribution in recently diagnosed ARV naïve pregnant women from Rio de Janeiro, Brazil. Methods: 299 blood samples of recently diagnosed HIV-1-infected pregnant women from four reference antenatal care public health units in Rio de Janeiro were consecutively collected and analyzed from 2005 to 2015.ViroseqTM (Abbott) and TrugeneTM HIV-1 Genotyping Systems (Siemens) were used for genotyping and the Standford Algorithm for Interpretation of HIV-1 Resistance for TDR and subtype identification. Results: The most prevalent HIV-1 subtype was the subtype B (77%), followed by subtype F (15%), BF recombinant forms (4%), subtype C (2%) and the recombinant forms: CRF02_AG, CRF31_BC and DF identified in one subject each. Overall, the TDR mutations was 11.7%, 2.7% associated to the Nucleoside Reverse Transcriptase Inhibitors (NRTIs) of the samples, 2.7% to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and 1% to Protease Inhibitors (PIs). Mutations associated with NRTI resistance were TAMs, F77L, M184V; associated with NNRTI resistance were K103N, Y188H and L100I and. mutations associated to PIs were D30N, M46I, and V82L. Conclusions: HIV-1 subtype B was the most prevalent subtype observed in our study. For the first time infections with the circulating recombinant forms CRF02_AG and CRF31_BC were described in a pregnant woman, suggesting the spread of African derived virus in Brazil and the introduction in Rio de Janeiro of the CRF31_BC coming from South Brazil. Our results strongly suggest the need of establishing a regular surveillance system for transmitted HIV-1 drug resistance in pregnant women in Brazil and its integration in antenatal care management policies for HIV-1 infected women should be considered.

Missed opportunities for earlier diagnosis of HIV infection in people living with HIV in Thailand.

HIV testing is the first step to making people living with HIV (PLHIV) aware of their status. Thailand is among the countries where antiretroviral therapy is initiated in PLHIV at the lowest CD4 cell counts. We aimed to quantify and characterize missed opportunity (MO) for earlier diagnosis of HIV infection in PLHIV in Thailand. The medical records of adults who were newly diagnosed with HIV between 2019 and 2020 at the two tertiary hospitals in Thailand were reviewed. A hospital visit due to an HIV clinical indicator disease but an HIV test was not performed was considered an MO for HIV testing. Of 422 newly diagnosed PLHIV, 60 persons (14.2%) presented with at least one MO, and 20 persons (33.3%) had more than one MO. In PLHIV with MO, the median (interquartile range) time between the first MO event and HIV diagnosis was 33.5 (7-166) days. The three most common clinical manifestations that were missed were skin manifestations (25.0%), unexplained weight loss (15.7%), and unexplained lymphadenopathy (14.3%). Anemia was a factor associated with MO for HIV diagnosis [odds ratio (OR) 2.24, 95% confidence interval (CI) 1.25-4.35; p = 0.018]. HIV screening reduced the risk of MO for HIV diagnosis (OR 0.53 95% CI 0.29-0.95; p = 0.032). In conclusion, MOs for earlier diagnosis of HIV infection occurred in both participating hospitals in Thailand. Skin manifestations were the most common clinical indicator diseases that were missed. HIV testing should be offered for patients with unexplained anemia. Campaigns for HIV screening tests should be promoted.

Features of the clinic and course of cutaneous and sexually transmitted diseases in HIV infected patients from the Volgograd region of Russia

HIV infection still remains an urgent problem of modern medicine. The incidence has continued to rise in recent years. The variety of clinical manifestations of the infection, not pathognomonic in the early stages, leads to misdiagnosis for an extended time period. The aim of the study was to assess the structure of skin diseases and sexually transmitted diseases in patients with HIV infections in the Volgograd region, to identify the features of the clinic and the course of these pathologies. A retrospective analysis of case histories of 306 HIV-infected patients who applied for medical care to dermatological institutions in Volgograd over the past 5 years was carried out. The authors describe the diverse features of the clinic, the course of skin diseases, syphilis and urogenital infections in patients with HIV infection. Knowledge of these signs of related specialties will allow for doctors to avoid treatment, diagnostic and tactical errors and will contribute to the early diagnosis of HIV infection and skin diseases and sexually transmitted diseases alike.

Immunofluorescence and two-dimensional visual analysis of HIV-1 p24 antigen in clinical samples enhanced by poly-T templated copper nanoparticles and QDs

In this study, we reported a dual-mode fluorescence and two-dimensional color and distance visual reading technique for HIV-1 p24 antigen immunoassay using polyT-templated Cu NPs as the bridge and signal. Mode 1 combined the phenomenon of Cu2+ and Cu NPs being distinguished by CdTe QDs using the ink jet printing technology, which was introduced to make test strips. In mode 2, a highly sensitive p24 antigen analysis method was developed by combining the characteristics of terminal deoxyribonucleotidyl transferase (TdT) catalyzed primer and dTTP substrate extension to generate polyT, and using polyT-templated Cu NPs as signal reporters. Mode 1 with QDs as signal reporters achieved color and distance visual reading analysis of p24 antigen at pg/mL level, whereas mode 2 with Cu NPs as signal reporters achieved fg/mL level analysis sensitivity. This method was used to quantify p24 antigen in the serum of 20 patients with acute HIV infection. The results were highly consistent with those of laboratory electrochemiluminescence immunoassay (ECLIA), quantitative viral RNA results from by polymerase chain reaction (PCR), and clinical diagnosis. The serum of 10 normal people and 16 patients suffering from other diseases had no discernible effect on the p24 antigen analysis method. Therefore, this work provides solutions for early diagnosis of HIV infection in the future, as well as for point-of-care testing (POCT) in remote areas.

Delayed diagnosis of human immunodeficiency virus infection in people diagnosed with syphilis: A nationwide cohort study from 2011 to 2018 in Japan

Early treatment of HIV infection depends on timely diagnosis, but many persons living with HIV/AIDS (PLWHA) are unaware of their infection. Though many patients seeking medical attention for sexually transmitted diseases have HIV, many patients’ HIV co-infection is undiagnosed in Japan. This is the first report to analyze the timing of syphilis infection in PLWHA of all ages through the use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), containing clinical data of the largest group of HIV-positive patients available in Japan. Overall, 1521 PLWHA (male 93.2%) newly diagnosed and started on antiretroviral therapy were identified in 2016, and 646 (42.5%) patients had a diagnosis of syphilis between 2011 and 2018. Although 100 patients were diagnosed with syphilis before their HIV diagnosis, only 17 (17.0%) had been tested for HIV. Over 50 patients per year became infected with syphilis even after their HIV diagnosis (2017, n = 65 (4.3%); 2018, n = 58 (3.8%)). Although early diagnosis of HIV infection is important, most syphilis patients in Japan had not been properly tested for HIV infection. Since a certain number of HIV patients developed syphilis after HIV diagnosis, education for newly diagnosed HIV patients is important.

Point-of-care tests detecting HIV nucleic acids for diagnosis of HIV-1 or HIV-2 infection in infants and children aged 18 months or less.

BackgroundThe standard method of diagnosing HIV in infants and children less than 18 months is with a nucleic acid amplification test reverse transcriptase polymerase chain reaction test (NAT RT‐PCR) detecting viral ribonucleic acid (RNA). Laboratory testing using the RT‐PCR platform for HIV infection is limited by poor access, logistical support, and delays in relaying test results and initiating therapy in low‐resource settings. The use of rapid diagnostic tests at or near the point‐of‐care (POC) can increase access to early diagnosis of HIV infection in infants and children less than 18 months of age and timely initiation of antiretroviral therapy (ART).ObjectivesTo summarize the diagnostic accuracy of point‐of‐care nucleic acid‐based testing (POC NAT) to detect HIV‐1/HIV‐2 infection in infants and children aged 18 months or less exposed to HIV infection.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (until 2 February 2021), MEDLINE and Embase (until 1 February 2021), and LILACS and Web of Science (until 2 February 2021) with no language or publication status restriction. We also searched conference websites and clinical trial registries, tracked reference lists of included studies and relevant systematic reviews, and consulted experts for potentially eligible studies.Selection criteriaWe defined POC tests as rapid diagnostic tests conducted at or near the patient site. We included any primary study that compared the results of a POC NAT to a reference standard of laboratory NAT RT‐PCR or total nucleic acid testing to detect the presence or absence of HIV infection denoted by HIV viral nucleic acids in infants and children aged 18 months or less who were exposed to HIV‐1/HIV‐2 infection. We included cross‐sectional, prospective, and retrospective study designs and those that provided sufficient data to create the 2 × 2 table to calculate sensitivity and specificity. We excluded diagnostic case control studies with healthy controls.Data collection and analysisWe extracted information on study characteristics using a pretested standardized data extraction form. We used the QUADAS‐2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the risk of bias and applicability concerns of the included studies. Two review authors independently selected and assessed the included studies, resolving any disagreements by consensus. The unit of analysis was the participant. We first conducted preliminary exploratory analyses by plotting estimates of sensitivity and specificity from each study on forest plots and in receiver operating characteristic (ROC) space. For the overall meta‐analyses, we pooled estimates of sensitivity and specificity using the bivariate meta‐analysis model at a common threshold (presence or absence of infection).Main resultsWe identified a total of 12 studies (15 evaluations, 15,120 participants). All studies were conducted in sub‐Saharan Africa. The ages of included infants and children in the evaluations were as follows: at birth (n = 6), ≤ 12 months (n = 3), ≤ 18 months (n = 5), and ≤ 24 months (n = 1). Ten evaluations were field evaluations of the POC NAT test at the point of care, and five were laboratory evaluations of the POC NAT tests.The POC NAT tests evaluated included Alere q HIV‐1/2 Detect qualitative test (recently renamed m‐PIMA q HIV‐1/2 Detect qualitative test) (n = 6), Xpert HIV‐1 qualitative test (n = 6), and SAMBA HIV‐1 qualitative test (n = 3).POC NAT pooled sensitivity and specificity (95% confidence interval (CI)) against laboratory reference standard tests were 98.6% (96.1 to 99.5) (15 evaluations, 1728 participants) and 99.9% (99.7 to 99.9) (15 evaluations, 13,392 participants) in infants and children ≤ 18 months.Risk of bias in the included studies was mostly low or unclear due to poor reporting. Five evaluations had some concerns for applicability for the index test, as they were POC tests evaluated in a laboratory setting, but there was no difference detected between settings in sensitivity (−1.3% (95% CI −4.1 to 1.5)); and specificity results were similar.Authors' conclusionsFor the diagnosis of HIV‐1/HIV‐2 infection, we found the sensitivity and specificity of POC NAT tests to be high in infants and children aged 18 months or less who were exposed to HIV infection.

A point-of-care rapid HIV-1 test using an isothermal recombinase-aided amplification and CRISPR Cas12a-mediated detection

Human immunodeficiency virus type one (HIV-1) infection is one of the major public health problems worldwide. Effective control of HIV-1 epidemic relies on early diagnosis of HIV-1 infection by using simple, rapid point-of-care test (POCT). An integrated assay was developed and evaluated in this study to combine a real-time isothermal reverse-transcription recombinase-aided amplification (rRT-RAA) and CRISPR Cas12a-mediated detection for HIV-1. The testing results could be directly observed with naked eye using a blue light imager, making it a suitable on-site testing assay. Our preliminary data indicated that the assay was capable of detecting 20 copies of purified HIV-1 DNA or RNA per reaction or as low as 123 copies/ml of HIV-1 viral load in clinical samples. When screening 155 clinical samples with or without HIV-1 infection, the sensitivity and specificity of the rRT-RAA assay were 98.95% (94/95) and 100% (60/60), respectively. The coefficient value was 0.986 when compared with the Chinese FDA approved HIV-1 RT-qPCR assay. Furthermore, the newly developed HIV-1 rRT-RAA assay could detect the major HIV-1 genotypes CRF01_AE, CRF07_BC, CRF08_BC, CRF08_BC and subtype B in China. Our preliminary results indicated that the rRT-RAA assay or its combination with CRISPR Cas12a-mediated detection could serve as a rapid, convenient, and robust assay for HIV-1 detection.

Antiretroviral Tenofovir Induces Senescence-Associated β-Galactosidase Activity in Primary Human Brain Vascular Cells in Multi-Layer Three-Dimensional Co-Culture

IntroductionIn the current context of early diagnosis of HIV infection, immediate initiation of antiretroviral (ARV) therapy, and lifelong chronic treatment, the potential ARV toxicity is of particular concern. Emtricitabine (FTC) and tenofovir (TFV) are commonly used as backbone drugs in ARV regimens recommended for initial therapy of HIV infection. Here we assessed the effects of FTC and TFV exposure on senescence-associated β-galactosidase (SA-β-Gal) activity, a marker of cellular senescence, in human brain vascular cells.DesignMulti-layer three-dimensional cell co-cultures and in vitro assays.MethodsTo mimic the small vessel wall structure in vivo, three types of primary human brain vascular cells (endothelial cells, smooth muscle cells, and pericytes) were co-cultured on three Alvetex Scaffold disks placed on top of each other in order (three-layer three-dimensional cell co-cultures) and exposed to clinically relevant concentrations of ARV drugs (FTC, TFV, or FTC+TFV combination) or vehicle for eight days (four or five biological replicates per condition, 18 replicates totally). The SA-β-Gal activity was quantitatively assayed in vitro by using the chemiluminescent Galacto-Star System (T1012; Applied Biosystems, Thermo Fisher Scientific, Waltham, MA) in 54 protein lysates extracted from individual cell-culture disks. Three-factor analysis of variance (cell type, FTC, TFV) was used to assess differences in the SA-β-Gal activity levels normalized by the corresponding total protein concentrations.ResultsThere was a trend for the FTC by TFV interaction effect on SA-β-Gal activity (P = 0.058). The effects of FTC and TFV were not significantly different among the three cell types. The overall effect of FTC was not significant when controlling for TFV and cell type. The overall effect of TFV was significant when controlling for FTC and cell type (F(1,48) = 30.61, P < 0.001, partial η2 = 0.389). In the absence of FTC, TFV raised SA-β-Gal activity by 0.631 units on average, regardless of cell type (P < 0.001, partial η2 = 0.368). In the presence of FTC, TFV raised SA-β-Gal activity by 0.303 units on average, regardless of cell type (P = 0.015, partial η2 = 0.118).ConclusionOur preliminary findings suggest that primary human brain vascular cells exposed to TFV at clinically relevant concentrations undergo cellular senescence. This potential adverse effect of TFV should be further studied in animal models of HIV infection.

Late presentation for HIV remains a major health issue in Spain: Results from a multicenter cohort study, 2004-2018.

ObjectivesWith the purpose of reducing the well-known negative impact of late presentation (LP) on people living with HIV (PLWH), guidelines on early HIV diagnosis were published in 2014 in Spain, but since then no data on LP prevalence have been published. To estimate prevalence and risk factors of LP and to evaluate their impact on the development of clinical outcomes in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) during 2004–2018.MethodsCoRIS is an open prospective multicenter cohort of PLWH, adults, naive to ART at entry. LP was defined as HIV diagnosis with CD4 count ≤350 cells/μL or an AIDS defining event (ADE). Multivariable Poisson regression models were used to estimate both prevalence ratios (PR) for the association of potential risk factors with LP and Incidence rate ratios (IRRs) for its impact on the development of the composite endpoint (first ADE, first serious non-AIDS event [SNAE] or overall mortality).Results14,876 individuals were included. Overall, LP prevalence in 2004–2018 was 44.6%. Risk factors for LP included older age, having been infected through injection drug use or heterosexual intercourse, low educational level and originating from non-European countries. LP was associated with an increased risk of the composite endpoint (IRR: 1.34; 95%CI 1.20, 1.50), ADE (1.39; 1.18, 1.64), SNAE (1.22; 1.01, 1.47) and mortality (1.71; 1.41, 2.08).ConclusionsLP remains a health problem in Spain, mainly among certain populations, and is associated with greater morbidity and mortality. Public policies should be implemented to expand screening and early diagnosis of HIV infection, for a focus on those at greatest risk of LP.

2021 European guideline on HIV testing in genito-urinary medicine settings.

Testing for HIV is critical for early diagnosis of HIV infection, providing long-term good health for the individual and prevention of onward transmission if antiretroviral treatment is initiated early. The main purpose of the 2021 European Guideline on HIV Testing in Genito-Urinary Settings is to provide advice on testing for HIV infection in individuals aged 16years and older who present to sexually transmitted infection, genito-urinary or dermato-venereology clinics across Europe. The guideline presents the details of best practice and offers practical guidance to clinicians and laboratories to identify and offer HIV testing to appropriate patient groups.

Evaluation of the efficiency of the various techniques used for screening of HIV in antenatal mothers to facilitate early initiation of treatment

The study has been conducted in pregnant women in the high risk category attending the antenatal O.P at M.N.R Hospital and medical college and Niloufer Hospital for a defined period. The screening tests for HIV used are Coombaids, (Dot Immunoassay), as per NACO guidelines & Fourth- Generation (double antigen/antibody Sandwich with solid micro wells pre-coated with Recombinant HIV-1gp41, HIV-1 Group O gp41, HIV-2 gp36, & amp; Monoclonal Anti p24 Antibodies. The individual sensitivity and specificity were evaluated and compared. The sera of all the women screened by COOMBAIDS were tested negative & out of all the negative samples one sample was tested positive by 4th generation ELISA. Hence, this study was carried out to evaluate the sensitivity and specificity of various techniques for Antibody detection and Antigen detection, and to determine the technique most suitable for early diagnosis of HIV infection.4 Keyword: Antenatal women, Specificity and Sensitivity.

Barriers to early diagnosis and treatment of severely immunosuppressed patients with HIV-1 infection: A quantitative and qualitative study.

To explore the barriers to early diagnosis of HIV infection and timely initiation of antiretroviral therapy (ART). We assessed the annual number and proportion of ART-naïve people living with HIV infection (PLWH) with severe immunosuppression in Shenzhen, China, from 2008 to 2019. Selected ART-naïve PLWHs with severe immunosuppression who were seeking treatment for the first time in the hospital in 2019 were subjected to an in-depth interview. The proportion of severely immunosuppressed, ART-naïve PLWH decreased from 36.73% in 2008 to 8.94% in 2015, and then plateaued at approximately 10% from 2015 to 2019. Overall, 55 patients, 70% of whom were men who had sex with men, participated in the qualitative interviews. Ten of them delayed treatment after diagnosis, with a median [interquartile range (IQR)] interval of 5.83 (3.98-8.54)years between diagnosis and ART. More than 80% of the patients reported casual sexual contact within a median period of 6years and with a median (IQR) of nine (4-20) casual sex partners. The major barriers to HIV testing and diagnosis included lack of knowledge about HIV and high-risk behaviours, low awareness about HIV testing, and resistance to HIV testing. The major barriers to ART initiation included lack of knowledge about the importance of ART and change of national ART eligibility policy, and HIV-related stress. The number of PLWHs with severe immunosuppression who seek treatment remains high in Shenzhen, China. Thus, current HIV-related care programmes targeting access to early diagnosis and treatment need to be improved.

Missed Opportunity Encounters for Early Diagnosis of HIV Infection in Adolescents.

Early diagnosis of HIV infection improves patient outcomes and reduces transmission. Adolescents make up one-fifth of new HIV diagnoses in the United States. We sought to quantify the number of missed opportunity encounters (MOEs) before HIV diagnosis for adolescents at a pediatric hospital (PediHosp) and a proximate adult hospital which employs universal HIV screening in its emergency department (ED) (CountyHosp). An observational study at 2 academic tertiary care hospitals in the United States that included all adolescents 13-20 years old with a new diagnosis of behaviorally-acquired HIV infection from 2006 to 2017. MOE were defined as any encounter at PediHosp or CountyHosp after the latter of the individual's 13th birthday or the date 3 months after the individual's most recent negative HIV screen, and before the encounter of HIV diagnosis. Comparisons were made by site of diagnosis and location of MOE. Two-hundred five subjects met inclusion criteria: 68% male, 76% Black and 81% men who have sex with men. There were 264 MOE, the proportion of adolescent ED encounters that were MOE at the PediHosp ED was 8.3 MOE per 10,000 encounters and the proportion at the CountyHosp ED was 1.2 (relative risk = 6.7; 95% CI: 4.1-11.0; P < 0.001). MOE for HIV diagnosis in adolescents occur frequently and are greater in number at a PediHosp as compared with a similar adult setting with universal screening. Universal HIV screening protocols at PediHosp may identify HIV-positive adolescents earlier.

Late Presenters of HIV Infection in an HIV Unit of a Tertiary University Hospital in a Rural Region of Greece.

A significant progress has been made over the years in the prognosis and treatment of patients with early diagnosis of HIV infection. However, late presentation of a large number of patients remains a serious public health problem. The aim of our study is to highlight the dimensions of the problem by evaluating the data from the HIV Unit of Alexandroupolis, a rural region with population heterogeneity and a strategic position between West and East, Europe, and Asia. This was a retrospective study, including 107 patients diagnosed with HIV infection in our unit from 2010 to 2018. Late presenters (LP) were defined as patients diagnosed with a CD4 cell count <350/mm3 or an AIDS-defining condition regardless of CD4 cell count. The proportion of patients diagnosed late was 49.5%. The majority were males in the age group 31-40 years (41.5%). Men who had sex with men were 37.8%. Among LP, 34% were at Center for Disease Prevention and Control stage C3. The most common AIDS-defining condition observed was Pneumocystis jirovecii Pneumonia (15.1%), followed by esophageal candidiasis (7.5%) and cryptococcal meningitis (3.8%). In addition, immune reconstitution inflammatory syndrome was documented (3.8%). A high percentage of patients were also coinfected with hepatitis B (22.6%) virus. The notably high percentage of LP in our unit demonstrates that late presentation remains a challenge for public health. Further efforts must be made to ensure an early diagnosis of HIV infection. The early initiation of antiretroviral therapy is vital to reduce viral load to undetectable levels and the risk of HIV transmission.

Acceptability and feasibility of testing for HIV infection at birth and linkage to care in rural and urban Zambia: a cross-sectional study

BackgroundEarly infant diagnosis is important for timely identification of HIV-infected infants and linkage to care. Testing at birth has been implemented to facilitate earlier diagnosis of HIV infection but may present new challenges. This study was conducted to understand the acceptability and feasibility of birth testing in urban and rural settings in southern Zambia.MethodsThis cross-sectional study was conducted at 11 hospitals and clinics in Livingstone, Choma, and Macha in Southern Province, Zambia from 2016 to 2018. Infants born to pregnant women living with HIV at the sites were eligible for enrollment. After enrollment, a questionnaire was administered to the mother and a dried blood spot card was collected from infants for testing at a central laboratory. When results were available, mothers were notified to return to the clinic. Acceptability of birth testing was evaluated based on the proportion of women who agreed to participate and the reasons for non-participation among women who declined. Feasibility of testing at birth was evaluated using turnaround times for returning results, the proportion of women receiving results, and linkage to care for infants testing positive.ResultsOne thousand four hundred three women were approached for the study. A small proportion declined due to refusal of birth testing (0 to 8.2% across sites). One thousand two hundred ninety women agreed to have their infants tested. The proportion of mothers receiving results ranged from 51.6 to 92.1%, and was significantly lower at the hospital than clinics in Livingstone (51.6% vs. 69.8%; p < 0.0001) and Macha (69.5% vs. 85.7%; p < 0.0001) but not Choma (85.7% vs. 92.1%; p = 0.34). For mothers who received test results, the median turnaround time from sample collection was 67 days in Livingstone and 53 days in Macha and Choma. Overall, 23 (1.8%) infants tested positive for HIV but only 8 (34.8%) were linked to care a median of 68 days (range: 29, 784) after sample collection.ConclusionsWhile testing at birth was acceptable, this study highlights the operational challenges under a centralized laboratory testing system. Point-of-care platforms are needed for rapid testing and return of results so HIV-infected children can be identified, linked to care, and treated as early as possible.

Nutritional, clinical and immunological status of children at HIV diagnosis in the continental region of Equatorial Guinea.

To evaluate the nutritional, clinical and immunological status of children at HIV diagnosis in the continental region of Equatorial Guinea. Children <18years diagnosed with HIV between 2009 and 2017 were included. Clinical, immunological and nutritional data were collected. Weight-for-height, weight-for-age and height-for-age Z-scores were calculated using WHO Child Growth Standards. The population was assessed in two equal periods (2009-2013 and 2014-2017) from the time of diagnosis. A total of 213 children were diagnosed with HIV (49.3% males), median age 3.8years (IQR: 1.5-8.2). A total of 121 cases (56.8%) were at WHO clinical stage III, and 53 (24.9%) were at WHO clinical stage IV. CDC immunological stage II was diagnosed in 51/130 (39.2%) and CDC stage III in 44/130 (33.8%). About 56.2% of children were underweight (weight-for-age <-2 SD); 20.1% moderately and 36.1% severely so. About 27.6% of children were wasted (weight-for-height <-2 SD); 11.9% moderately and 15.7% severely so. About 56.3% of children were stunted (height-for-age <-2 SD); 20.7% moderately and 35.6% severely so. The prevalence of wasting was higher in children ≤5years than in children >5years (36.4% vs. 19.1%, P=0.026). In the second period, the prevalence of moderate-severe immunodeficiency decreased (87.2% to 67.0%, P=0.018), without significant differences in the other nutritional or clinical data. Severe underweight was a risk factor for moderate-severe immunodeficiency (aOR: 4 [95% CI: 1.4-11.4], P=0.010). We highlight a high proportion of malnutrition at the time of HIV diagnosis in Guinea´s paediatric population. Early diagnosis of HIV infection is a priority, achievable by training Guinea´s physicians to suspect HIV early, introducing HIV molecular diagnostic techniques and ensuring intensive nutritional treatment.

Evolving complexities of infant HIV diagnosis within Prevention of Mother-to-Child Transmission programs.

Early diagnosis of HIV infection among infants and children is critical as prompt initiation of antiretroviral therapy prevents morbidity and death. Yet despite advances in the accuracy and availability of infant HIV diagnostic testing, there are increasing challenges with making an early definitive diagnosis. These challenges relate primarily to advances in prevention of mother-to-child transmission (PMTCT) of HIV. Although PMTCT programs have proven to be highly effective in reducing infant HIV infection, infants who are HIV-infected may achieve virological suppression and loss of detectability of HIV nucleic acid prior to diagnosis because of antiretroviral drug exposure. Hence, false-negative and indeterminate HIV polymerase chain reaction (PCR) results can occur, especially among high-risk infants given multi-drug prophylactic regimens. However, the infant HIV diagnostic landscape is also complicated by the inevitable decline in the positive predictive value of early infant diagnosis (EID) assays. As PMTCT programs successfully reduce the mother-to-child transmission rate, the proportion of false-positive EID results will increase. Consequently, false-negative and false-positive HIV PCR results are increasingly likely despite highly accurate diagnostic assays. The problem is compounded by the seemingly intractable prevalence of maternal HIV within some settings, resulting in a considerable absolute burden of HIV-infected infants despite a low mother-to-child transmission rate.