Acute HIV Infection Cases Research Articles

Outcomes of discordant HIV screening test results at a southern academic medical center.

The aim of this study was to examine outcomes of follow-up for persons with discordant fourth-generation HIV screening test results. A retrospective chart review. We analyzed the electronic health record at the Medical University of South Carolina for a 10-year period spanning 2012-2022 to identify instances of discordant HIV screening test results, wherein initial antigen/antibody screening was positive, but reflex confirmatory testing for HIV-1 and HIV-2 antibodies was negative. We reviewed individual records to evaluate clinical follow-up and determine if the discordant test represented an acute HIV infection, a false-positive result, or was unresolved. We identified 199 testing instances with discordant results. Most discordant results ( n = 115) were subsequently determined to reflect a false-positive test, while 56 were unresolved without documented follow-up testing. Twenty-eight cases of acute HIV infection were identified of which 26 were linked to care within a month of initial testing. Two acute HIV cases were not identified in real time leading to delay in diagnosis and care. Testing done in the context of infectious symptoms and testing performed in the emergency department were associated with increased odds of a discordant test ultimately reflecting acute HIV infection. These results demonstrate the importance of appropriate and timely follow-up for discordant HIV screening test results.

A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics.

IntroductionHIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio‐sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi.MethodsWe conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV‐seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV‐seronegative (one negative rapid test) and ‐serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants’ sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant.ResultsA total of 1230 HIV‐seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV‐seronegative or ‐serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant.ConclusionsCombining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio‐sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio‐sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness.

LB-6. Increased Diagnoses of Acute HIV Infection through Routine ED Screening and Rapid Linkage to Care and initiation of HAART During the COVID-19 Pandemic

BackgroundThe COVID-19 pandemic has negatively impacted routine HIV screening in healthcare settings. This has serious implications, especially for patients with acute HIV infection (AHI) presenting with symptoms suggesting COVID-19 infection. This is a high priority population for rapid linkage to care (LTC) and initiation of HAART.MethodsWe reviewed data from our eXpanded HIV Testing and LTC (X-TLC) Program, a collaboration effort between 13 healthcare centers on the South and West Sides of Chicago. Since 2016, most sites had 4th or 5th generation HIV Ag/Ab testing available.ResultsMost sites experienced reductions in HIV screens during the COVID-19 pandemic. Advanced planning by our ED incorporated blood draws for HIV screens as part of COVID-19 evaluations. UCM performed 19,111 HIV screens (11,133 in the ED) between 1/1/20 and 8/17/20, along with 100,635 COVID PCRs (14,754 in ED) between 3/17/20 and 8/17/20. Nine patients were diagnosed with AHI after the first case of COVID-19 in Chicago (1/24/20), and 7 were diagnosed after the first case of community transmission in Cook County (3/8/20). All cases of AHI were diagnosed in the ED. The rate of AHI was significantly higher in 2020 versus the prior 4 years (14.4 vs 6.8 per year, p < 0.05). AHI patients comprised 25.7 % (9/35) of all new diagnoses, the highest percent ever. There were 7 men (6 identified as MSM) and 2 cis-gender women, median age of 25 years (21 to 28 years). The median viral load was 6 million (115,000 to > 6 million) copies/mL. Eight of 9 patients presented with an illness indistinguishable from COVID-19, including 1co-infected patient. All were LTC and started on HAART from time of PCR result within a median of 1 day (0–38), but 3 days (range 1–41) from sample collection as a result of delayed reflex PCR confirmatory testing due to high demands on lab personnel and scarcity of reagents due to COVID-19 PCR volumes (since resolved).HIV Screening and COVID-19 Testing in the ED During COVID-19 ConclusionContinued HIV screening in our ED during the COVID-19 pandemic identified an increased number of patients with AHI. These individuals may be more likely to present for care due to fear of COVID-19 infection. We achieved rapid LTC and initiation of HAART without any incremental increases in resources. All HIV screening programs should incorporate blood-based HIV screening into their COVID-19 testing programs.Disclosures Moira McNulty, MD, MS, Gilead Sciences (Grant/Research Support)

Clinical and laboratory characterictic of acute HIV-infection in adult residents of Novosibirsk region

Purpose of the study. To study the characteristics of acute HIV infection in adults in the Novosibirsk region in 2017– 2018.Materials and methods. 200 patients with acute HIV infection, residents of the Novosibirsk region, aged 15 to 74 years, hospitalized in 2017–2018, 104 men and 96 women were examined. The diagnosis was verified by detecting antibodies to HIV in ELISA with a negative or doubtful result of the immunoblot, as well as by determining the quantitative content of HIV RNA in the blood by PCR. The hemogram, the content of CD4 + lymphocytes in the blood were determined. In addition, HIV-1 was studied in 71 patients for belonging to a genetic group.Results. Patients of 20–40 years old prevailed – 70.5%. The sexual way was dominant in women (69.0%), injecting psychoactive substances was more often in men (32.2%). Frequent symptoms were fever (99%), exanthema (65.5%), polylimfoadenopathy (54.0%). Less common were diarrhea (36.0%), pharyngotonsillitis (23.0%), aphthous stomatitis (6.5%), hepatomegaly or hepatosplenomegaly (8.5%). Secondary diseases were revealed in 26.5% of patients. Leukopenia was recorded in 63.0%, thrombocytopenia in 62.5%, lymphocytosis and atypical cells of the lymphoid series in 14.0%. All patients had a high “viral load” – from 23,000 to 10,000,000 or more copies / ml, a decrease in the number of CD4 + less than 350 cells – in 38.0%. From among 71 patients, 19.7% had HIV-1 subtype A, and 76.0% had recombinant HIV-1 CRF63_02A. In the latter, “viral load” of more than 10,000,000 copies / ml was more often recorded (67.8% vs. 33.4%, p = 0.004).Conclusion. A significant number of cases of acute HIV infection were reported in the Novosibirsk region in 2017– 2018. Its detection is possible by examination of all febrile patients who apply to medical institutions. Early initiation of antiretroviral therapy with the appointment of well-tolerated regimens contributes to the formation of a high commitment to therapy.

Brief Report: The Amsterdam Symptom and Risk-Based Score Predicts for Acute HIV Infection in Men Who Have Sex With Men in San Diego.

Dijkstra et al recently described a risk- and symptom-based score moderately predictive for HIV seroconversion in the preceding 6-12 months in men who have sex with men (MSM) in Amsterdam. Our objective was to determine whether this "Amsterdam Score" could also predict for acute HIV infection (AHI) in MSM. This study is a case-control analysis of a prospectively enrolled cohort of MSM who voluntarily presented for HIV testing in San Diego. The study sample was composed of MSM who screened HIV antibody-negative and then either tested positive with AHI [HIV nucleic acid test (NAT)-positive] or tested HIV NAT-negative. The Amsterdam Score was calculated for each participant in the study sample. Score performance was assessed using receiver operating characteristic curves and their area under the curve (AUC). An optimal cutoff was determined using the Youden index. Seven hundred fifty-seven MSM (110 AHI and 647 HIV NAT-negative) were included in the analysis. AHI and HIV-negative cases were similar in age [median 32 years (interquartile range 26-42) vs 33 (27-45), respectively, P = 0.082]. The Amsterdam Score yielded a receiver operating characteristic curve with an AUC of 0.88 (95% confidence interval: 0.84 to 0.91). An optimal cutoff of ≥1.6 was 78.2% sensitive and 81.0% specific. The risk- and symptom-based Amsterdam Score was highly predictive (AUC of 0.88) of AHI in MSM in San Diego. The Amsterdam Score could be used to target NAT utilization in resource-poor settings among MSM who test HIV antibody-negative, although the potential cost-savings must be balanced with the risk of missing AHI diagnoses.

Rapid Clinical Progression Among Acute HIV-Infected Men Who Have Sex with Men in China: Findings from a 5-Year Multicenter Prospective Cohort Study

Background: In an era of anti-retroviral therapy (ART) and proven risk-reduction strategies, more detailed information is needed on rapid HIV clinical progression among men who have sex with men (MSM) in Asia. We monitored clinical progression in Chinese MSM with acute HIV infection (AHI). Methods: During 2009-2014, we identified 400 AHI cases via periodic testing of 4932 MSM in China. Men with two consecutive CD4 T-cell counts <350 cells/μL within 3-24 months post-infection were considered rapid progressors (RPs). We used Cox models adjusted for sociodemographics to identify factors associated with rapid progression. Findings: Among 400 AHI cases, 46·5% were RPs; 35·1% reached RP status by 12 months post-infection and 63·9% by 24 months. Rapid progression was associated with herpes simplex-2 co-infection (adjusted hazard ratio 1·7, 95% confidence interval 1·2-2·3), depression (1·9, 1·5-2·6), baseline CD4 T-cell count <500/μL (3·5, 2·4-5·1), higher baseline HIV viral load (VL; 1·6, 1·2-2·3), acute symptoms lasting ≥2 weeks (1·6, 1·1-2·2), higher body mass index (0·9, 0·9-1·0), higher HIV VL (1·7, 1·4-2·1) and set point VL (2·0, 1·6-2·5) at 3 months, each 100 cells/μL decrease in CD4 T-cell count at 3 months (2·2, 1·9-2·5), and baseline routine blood tests (medians of white blood cell count, hemoglobin, mean corpuscular hemoglobin and hemoglobin concentration, platelet count and mean volume, lymphocytes, and mixed cell count; all P<0·05). Interpretation Patients diagnosed with AHI, particularly those with RP indicators, should receive immediate ART. AHI screening and regular CD4 T-cell/HIV-VL monitoring among high-risk groups in routine clinical practice are needed. Funding: None. Declaration of interests: All other authors declare no competing interests. Ethics Approval Statement: The Ethics Committee of The First Affiliated Hospital of China Medical University reviewed and approved the study protocol ([2008]73). Written informed consent was obtained from each participant before study enrollment.

Comparison of turnaround time and total cost of HIV testing before and after implementation of the 2014 CDC/APHL Laboratory Testing Algorithm for diagnosis of HIV infection

BackgroundUpdated recommendations for HIV diagnostic laboratory testing published by the Centers for Disease Control and Prevention and the Association of Public Health Laboratories incorporate 4th generation HIV immunoassays, which are capable of identifying HIV infection prior to seroconversion. ObjectivesThe purpose of this study was to compare turnaround time and cost between 3rd and 4th generation HIV immunoassay-based testing algorithms for initially reactive results. Study DesignThe clinical microbiology laboratory database at Mayo Clinic, Rochester, MN was queried for 3rd generation (from November 2012 to May 2014) and 4th generation (from May 2014 to November 2015) HIV immunoassay results. All results from downstream supplemental testing were recorded. Turnaround time (defined as the time of initial sample receipt in the laboratory to the time the final supplemental test in the algorithm was resulted) and cost (based on 2016 Medicare reimbursement rates) were assessed. ResultsA total of 76,454 and 78,998 initial tests were performed during the study period using the 3rd generation and 4th generation HIV immunoassays, respectively. There were 516 (0.7%) and 581 (0.7%) total initially reactive results, respectively. Of these, 304 (58.9%) and 457 (78.7%) were positive by supplemental testing. There were 10 (0.01%) cases of acute HIV infection identified with the 4th generation algorithm. The most frequent tests performed to confirm an HIV-positive case using the 3rd generation algorithm, which were reactive initial immunoassay and positive HIV-1 Western blot, took a median time of 1.1 days to complete at a cost of $45.00. In contrast, the most frequent tests performed to confirm an HIV-positive case using the 4th generation algorithm, which included a reactive initial immunoassay and positive HIV-1/-2 antibody differentiation immunoassay for HIV-1, took a median time of 0.4 days and cost $63.25. Overall median turnaround time was 2.2 and 1.5 days, and overall median cost was $63.90 and $72.50 for 3rd and 4th generation algorithms, respectively. ConclusionsBoth 3rd and 4th generation HIV immunoassays had similar total numbers of tests performed and positivity rates during the study period. A greater proportion of reactive 4th generation immunoassays were confirmed to be positive, and the 4th generation algorithm identified several cases of acute HIV infection that would have been missed by the 3rd generation algorithm. The 4th generation algorithm had a more rapid turnaround time but higher cost for confirmed positive HIV infections and overall, compared to the 3rd generation algorithm.

High Feasibility of Empiric HIV Treatment for Patients With Suspected Acute HIV in an Emergency Department.

Earlier intervention in acute HIV infection limits HIV reservoirs and may decrease HIV transmission. We developed criteria for empiric antiretroviral therapy (ART) in an emergency department (ED) routine HIV screening program. We assessed the feasibility and willingness of patients with suspected acute HIV infection in the ED to begin ART. A suspected acute HIV infection was defined as a positive HIV antigen antibody combination immunoassay with pending HIV-antibody differentiation test results and HIV RNA viral load. During the study period, there were 16 confirmed cases of acute HIV infection: 11 met our criteria for empiric ART and agreed to treatment, 10 were prescribed ART, and 1 left the ED against medical advice without a prescription for ART. Eight patients completed at least one follow-up visit. Empiric HIV treatment in an ED is feasible, well received by patients, and offers a unique entry point into the HIV care continuum.

Ten Years of Screening and Testing for Acute HIV Infection in North Carolina.

To describe demographic and behavioral characteristics of persons with acute HIV infection (AHI) over time. We conducted a retrospective assessment of AHI identified through the Screening and Tracing Active Transmission (STAT) program from 2003 to 2012 in North Carolina (NC). AHI was identified using pooled nucleic acid amplification for antibody negative samples and individual HIV-1 RNA for antibody indeterminate samples. The STAT program provides rapid notification and evaluation. We compared STAT-collected demographic and risk characteristics with all persons requesting tests and all non-AHI diagnoses from the NC State Laboratory of Public Health. The STAT Program identified 236 AHI cases representing 3.4% (95% confidence interval: 3.0% to 3.9%) of all HIV diagnoses. AHI cases were similar to those diagnosed during established HIV. On pretest risk-assessments, AHI cases were predominately black (69.1%), male (80.1%), young (46.8% < 25 years), and men who have sex with men (MSM) (51.7%). Per postdiagnosis interviews, the median age decreased from 35 (interquartile range 25-42) to 27 (interquartile range 22-37) years, and the proportion <25 years increased from 23.8% to 45.2% (trend P = 0.04) between 2003 and 2012. AHI men were more likely to report MSM risk post-diagnosis than on pretest risk-assessments (64%-82.9%; P < 0.0001). Post-diagnosis report of MSM risk in men with AHI increased from 71.4% to 96.2%. In NC, 3.4% of individuals diagnosed with HIV infection have AHI. AHI screening provides a real-time source of incidence trends, improves the diagnostic yield of HIV testing, and offers an opportunity to limit onward transmission.

Targeting the use of pooled HIV RNA screening to reduce cost in health department STD clinics: New York City, 2009-2011.

Staff at public New York City sexually transmitted disease (STD) clinics screen patients for acute HIV infection (AHI) using pooled nucleic acid amplification tests. AHI screening is expensive but important for populations at high risk of acquiring HIV. We analyzed if targeting AHI screening in STD clinics could reduce program costs while maintaining AHI case detection. From January 2009 through May 2010, we screened all patients with negative rapid HIV tests for AHI. Using risk information on cases detected during this universal screening period, we developed criteria for targeted AHI screening and compared case yields and testing costs during 12 months of universal screening (June 2009 through May 2010) vs. 12 months of targeted screening (June 2010 through May 2011). During the defined period of universal screening, we identified 40 AHI cases, and during targeted screening, we identified 35 AHI cases. Because of targeting efforts, the number needed to test to find one AHI case dropped from 1,631 to 254. With targeted screening, it cost an average of $4,535 per case detected and 39.3 cases were detected per 10,000 specimens; using universal screening, $29,088 was spent per case detected and 6.1 cases were detected per 10,000 specimens processed. Targeted screening identified similar numbers of AHI cases as when screening all clinic patients seeking HIV testing, but at one-seventh the cost.

Evaluating New Definitions of Acute and Early HIV Infection from HIV Surveillance Data.

Background : The U.S. HIV staging system is being revised to more comprehensively track early and acute HIV infection (AHI). We evaluated our ability to identify known cases of AHI using King County (KC) HIV surveillance data.Methodology : AHI cases were men who have sex with men (MSM) with negative antibody and positive pooled nucleic acid amplification (NAAT) tests identified through KC testing sites. We used KC surveillance data to calculate inter-test intervals (ITI, time from last negative to first positive test) and the serologic algorithm for recent HIV seroconversion (STARHS). For surveillance data, AHI was defined as an ITI of ≤ 30 days and early infection as an ITI ≤ 180 days or STARHS recent result. Dates of last negative HIV tests were obtained from lab reports in the HIV surveillance system or data collected for HIV Incidence Surveillance.Results : Between 2005 and 2011, 47 MSM with AHI were identified by pooled NAAT. Of the 47 cases, 36% had ITI < 1 day, 60% had an ITI < 30 days, and 70% (95% CI=55-82%) had an ITI ≤ 6 months and would have been identified as early HIV infection. Of the 47, 38% had STARHS testing and 94% were STARHS recent.Conclusion : MSM with known AHI were not identified by proposed definitions of AHI and early infection. These known AHI cases were frequently missed by HIV surveillance because concurrent negative antibody tests were not reported. Successful implementation of the revisions to the HIV staging system will require more comprehensive reporting.

Pooled nucleic acid testing increases the diagnostic yield of acute HIV infections in a high-risk population compared to 3rd and 4th generation HIV enzyme immunoassays

ObjectivesWe compared a 3rd generation (gen) and two 4th gen HIV enzyme immunoassays (EIA) to pooled nucleic acid testing (PNAT) for the identification of pre- and early seroconversion acute HIV infection (AHI). Study Design9550 specimens from males >18 year from clinics attended by men who have sex with men were tested by Siemens ADVIA Centaur® HIV 1/O/2 (3rd gen) and HIV Combo (4th gen), as well as by Abbott ARCHITECT® HIV Ag/Ab Combo (4th gen). Third gen non-reactive specimens were also tested by Roche COBAS® Ampliprep/COBAS® TaqMan HIV-1 Test v.2 in pools of 24 samples. Sensitivity and specificity of the three EIAs for AHI detection were compared. Results7348 persons contributed 9435 specimens and had no evidence of HIV infection, 79 (94 specimens) had established HIV infection, 6 (9 specimens) had pre-seroconversion AHI and 9 (12 specimens) had early seroconversion AHI. Pre-seroconversion AHI cases were not detected by 3rd gen EIA, whereas 2/6 (33.3%) were detected by Siemens 4th gen, 4/6 (66.7%) by Abbott 4th gen and 6/6 (100%) by PNAT. All three EIAs and PNAT detected all individuals with early seroconversion AHI. Overall sensitivity/specificity for the EIAs relative to WB or NAT resolved infection status was 93.6%/99.9% for Siemens 3rd gen, 95.7%/99.7% for Siemens 4th gen and 97.9%/99.2% for Abbott 4th gen. ConclusionsWhile both 4th gen EIAs demonstrated improved sensitivity for AHI compared to 3rd gen EIA, PNAT identified more AHI cases than either 4th gen assay. PNAT is likely to remain a useful strategy to identify AHI in high-risk populations.

Leveraging a Rapid, Round-the-Clock HIV Testing System to Screen for Acute HIV Infection in a Large Urban Public Medical Center

To describe the prevalence and location of new and acute HIV diagnoses in a large urban medical center. Secondary objectives were to evaluate rapid HIV test performance, the added yield of acute HIV screening, and linkage-to-care outcomes. Cross-sectional study from November 1, 2008, to April 30, 2009. The hospital laboratory performed round-the-clock rapid HIV antibody testing on venipuncture specimens from patients undergoing HIV testing in hospital and community clinics, inpatient settings, and the emergency department (ED). For patients with negative results, a public health laboratory conducted pooled HIV RNA testing for acute HIV infection. The laboratories communicated positive results from the hospital campus to a linkage team. Linkage was defined as 1 outpatient HIV-related visit. Among 7927 patients, 8550 rapid tests resulted in 137 cases of HIV infection [1.7%, 95% confidence interval (CI): 1.5% to 2.0%], of whom 46 were new HIV diagnoses (0.58%, 95% CI: 0.43% to 0.77%). Pooled HIV RNA testing of 6704 specimens (78.4%) resulted in 3 cases of acute HIV infection (0.05%, 95% CI: 0.01% to 0.14%) and increased HIV case detection by 3.5%. Half of new HIV diagnoses and two thirds of acute infections were detected in the ED and urgent care clinic. Rapid test sensitivity was 98.9% (95% CI: 93.8% to 99.8%) and the specificity 99.9% (95% CI: 99.7% to 99.9%). More than 95% of newly diagnosed and out-of-care HIV-infected patients were linked to care. Patients undergoing HIV testing in EDs and urgent care clinics may benefit from being simultaneously screened for acute HIV infection.

O1-S11.04 Targeting the use of HIV RNA screening to maximise yield and minimise cost: NYC Health Department STD Clinics, 2008–2010

BackgroundNucleic acid amplification testing (NAAT) is an important tool for identifying acute HIV infection (AHI), a period of high infectivity when antibody is undetectable. NAAT pooling methods (pNAAT) help contain...

Detection of acute HIV infections among sexually transmitted disease clinic patients: a practice in Guangxi Zhuang Autonomous Region, China

Detection of people with acute HIV infection (AHI) affords an important opportunity for early HIV treatment and prevention. HIV RNA reverse transcriptase-polymerase chain reaction (RT-PCR) testing with two-stage pooling scheme...

Improved detection of acute HIV-1 infection in sub-Saharan Africa: development of a risk score algorithm

Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals. A cross-sectional study of 1448 adults attending a sexually transmitted infections (STI) clinic in Malawi. Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test results, and STI syndromes that were predictive of AHI. We assigned a model-based score to each predictor and calculated a risk score for each participant. Twenty-one participants (1.45%) had AHI, 588 had established HIV infection, and 839 were HIV-negative. AHI was strongly associated with discordant rapid HIV tests and genital ulcer disease (GUD). The algorithm also included diarrhea, more than one sexual partner in 2 months, body ache, and fever. Corresponding predictor scores were 1 for fever, body ache, and more than one partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI. Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.