Rapid Testing Algorithm Research Articles

Lessons learnt from assessing and improving accuracy and positive predictive value of the national HIV testing algorithm in Nigeria.

HIV testing remains an entry point into HIV care and treatment services. In 2007, Nigeria adopted and implemented a two-test rapid HIV testing algorithm of three HIV rapid test kits, following the sequence: Alere Determine (first test), UnigoldTM (second test), and STAT-PAK® as the tie-breaker. Sub-analysis of the 2018 Nigeria HIV/AIDS Indicator and Impact Survey data showed significant discordance between the first and second tests, necessitating an evaluation of the algorithm. This manuscript highlights lessons learnt from that evaluation. A two-phased evaluation method was employed, including abstraction and analysis of retrospective HIV testing data from January 2017 to December 2019 from 24 selected sites supported by the United States President's Emergency Plan for AIDS Relief programme. A prospective evaluation of HIV testing was done among 2895 consecutively enrolled and consented adults, aged 15-64 years, accessing HIV testing services from three selected sites per state across the six geopolitical zones of Nigeria between July 2020 and September 2020. The prospective evaluation was performed both in the field and at the National Reference Laboratory under controlled laboratory conditions. Stakeholder engagements, strategic selection and training of study personnel, and integrated supportive supervision were employed to assure the quality of evaluation procedures and outcomes. The algorithm showed higher sensitivity and specificity in the National Reference Laboratory compared with the field. The approaches to quality assurance were integral to the high-quality study outcomes. We recommend comparison of testing algorithms under evaluation against a gold standard. This study provides context-specific considerations in using World Health Organization recommendations to evaluate the Nigerian national HIV rapid testing algorithm.

Trends in HIV prevalence, incidence, and progress towards the UNAIDS 95-95-95 targets in Malawi among individuals aged 15–64 years: population-based HIV impact assessments, 2015−16 and 2020−21

In 2014, UNAIDS set the goal of ending the AIDS epidemic by 2030 through the achievement of testing and treatment cascade targets. To evaluate progress achieved and highlight persisting gaps in HIV epidemic control in Malawi, we aimed to compare key indicators (prevalence, incidence, viral load suppression, and UNAIDS 95-95-95 targets) from the 2015-16 and 2020-21 Malawi Population-based HIV Impact Assessment (PHIA) survey results. The Malawi PHIAs were nationally representative, cross-sectional surveys with a two-stage cluster sampling design. The first survey was conducted between Nov 27, 2015, and Aug 26, 2016; the second survey was conducted between Jan 15, 2020, and April 26, 2021. Our analysis included survey participants aged 15-64 years. Participants were interviewed and a 14 mL blood sample was collected and tested for HIV infection using the national rapid testing algorithm. For each survey, we estimated key HIV epidemic indicators and achievement of 95-95-95 targets. The risk ratio (RR) of the indicators between surveys were computed and considered significant at a confidence level of 0·05. All results were weighted, and self-reported awareness and treatment status were adjusted to account for detection of antiretrovirals. Our analysis included 17 187 participants aged 15-64 years in 2015-16 and 21 208 in 2020-21 who participated in the surveys and blood draw. In the 2020-21 survey, 88·4% (95% CI 86·7-90·0) of people living with HIV were aware of their HIV-positive status; of those aware, 97·8% (97·1-98·5) were on antiretroviral therapy; and of those on treatment, 96·9% (95·9-97·7) were virally suppressed. Between surveys, the national HIV prevalence decreased significantly from 10·6% (10·0-11·2) to 8·9% (8·4-9·5) with RR 0·85 (95% CI 0·78-0·92; p<0·0001). The annual HIV incidence decreased from 0·37% (0·20-0·53) to 0·22% (0·11-0·34) with RR 0·61 (95% CI 0·31-1·20; p=0·15). The population viral load suppression increased from 68·3% (66·0-70·7) in 2015-16 to 87·0% (85·3-88·5) in 2020-21 (RR 1·27 [95% CI 1·22-1·32]; p<0·0001). These results suggest that Malawi had already surpassed the UNAIDS viral load suppression target for 2030 (85·7%) by 2020-21. Through strategies and evidence-informed interventions implemented in the last half decade, especially scale-up of effective HIV treatment, Malawi has made tremendous progress, including decreasing HIV prevalence and incidence and achieving both the second and third 95 targets ahead of 2030. To address the first 95, efforts in HIV diagnosis should focus on males and younger age groups. There is a continued need for effective linkage to care, retention on antiretroviral therapy, and adherence support to maintain and build on progress. US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

Improving Lyme disease testing with data driven test design in pediatrics

Diagnostic advances have not kept pace with the expansion of Lyme disease caused by Borrelia burgdorferi and transmitted by ticks. Lyme disease clinical manifestations can overlap with many other diagnoses making Lyme disease a critical part of many differential diagnoses in endemic areas. Current diagnostic blood tests rely on a 2-tiered algorithm for which the second step is either a time-consuming western blot or a whole cell lysate immunoassay. Neither of these second step tests allow for rapid results of this critical rule out test. We hypothesized that using western blot confirmation information, we could create computational models to propose recombinant second-tier tests that would allow for more rapid, automated, and specific testing algorithms. We propose here a framework for assessing retrospective data to determine putative recombinant assay components. A retrospective pediatric cohort of 2755 samples submitted for Lyme disease screening was assessed using support vector machine learning algorithms to optimize tier 1 diagnostic thresholds for the Vidas IgG II assay and determine optimal tier 2 components for both a positive and negative confirmation test. In cases where the tier 1 screen was negative, but clinical suspicion was high, we found that 1 protein (L58) could be used to reduce false-negative results. For second-tier testing of screen positive cases, we found that 6 proteins could be used to reduce false-positive results (L18, L39M, L39, L41, L45, and L58) with a final machine learning classifier or 2 proteins using a final rules-based approach (L41, L18). This led to an overall accuracy of 92.36% for the proposed algorithm without a final machine learning classifier and 92.12% with integration of the machine learning classifier in the final algorithm when compared to the IgG western blot as the gold-standard. Use of this framework across multiple assays and institutions will allow for a data-driven approach to assay development to provide laboratories and patients with the improvements in turnaround time needed for this testing.

Estimation of HIV-1 Incidence Using a Testing History-Based Method; Analysis From the Population-Based HIV Impact Assessment Survey Data in 12 African Countries.

Estimating HIV incidence is essential to monitoring progress in sub-Saharan African nations toward global epidemic control. One method for incidence estimation is to test nationally representative samples using laboratory-based incidence assays. An alternative method based on reported HIV testing history and the proportion of undiagnosed infections has recently been described. We applied an HIV incidence estimation method which uses history of testing to nationally representative cross-sectional survey data from 12 sub-Saharan African nations with varying country-specific HIV prevalence. We compared these estimates with those derived from laboratory-based incidence assays. Participants were tested for HIV using the national rapid test algorithm and asked about prior HIV testing, date and result of their most recent test, and date of antiretroviral therapy initiation. The testing history-based method consistently produced results that are comparable and strongly correlated with estimates produced using a laboratory-based HIV incidence assay (ρ = 0.85). The testing history-based method produced incidence estimates that were more precise compared with the biomarker-based method. The testing history-based method identified sex-, age-, and geographic location-specific differences in incidence that were not detected using the biomarker-based method. The testing history-based method estimates are more precise and can produce age-specific and sex-specific incidence estimates that are informative for programmatic decisions. The method also allows for comparisons of the HIV transmission rate and other components of HIV incidence among and within countries. The testing history-based method is a useful tool for estimating and validating HIV incidence from cross-sectional survey data.

Evaluation of the Nigeria national HIV rapid testing algorithm.

Human Immunodeficiency Virus (HIV) diagnosis remains the gateway to HIV care and treatment. However, due to changes in HIV prevalence and testing coverage across different geopolitical zones, it is crucial to evaluate the national HIV testing algorithm as false positivity due to low prevalence could be detrimental to both the client and the service delivery. Therefore, we evaluated the performance of the national HIV rapid testing algorithm using specimens collected from multiple HIV testing services (HTS) sites and compared the results from different HIV prevalence levels across the six geopolitical zones of Nigeria. The evaluation employed a dual approach, retrospective, and prospective. The retrospective evaluation focused on a desktop review of program data (n = 492,880) collated from patients attending routine HTS from six geopolitical zones of Nigeria between January 2017 and December 2019. The prospective component utilized samples (n = 2,895) collected from the field at the HTS and tested using the current national serial HIV rapid testing algorithm. These samples were transported to the National Reference Laboratory (NRL), Abuja, and were re-tested using the national HIV rapid testing algorithm and HIV-1/2 supplementary assays (Geenius to confirm positives and resolve discordance and multiplex assay). The retrospective component of the study revealed that the overall proportion of HIV positives, based on the selected areas, was 5.7% (28,319/492,880) within the study period, and the discordant rate between tests 1 and 2 was 1.1%. The prospective component of the study indicated no significant differences between the test performed at the field using the national HIV rapid testing algorithm and the re-testing performed at the NRL. The comparison between the test performed at the field using the national HIV rapid testing algorithm and Geenius HIV-1/2 supplementary assay showed an agreement rate of 95.2%, while that of the NRL was 99.3%. In addition, the comparison of the field results with HIV multiplex assay indicated a sensitivity of 96.6%, the specificity of 98.2%, PPV of 97.0%, and Kappa Statistic of 0.95, and that of the NRL with HIV multiplex assay was 99.2%, 99.4%, 99.0%, and 0.99, respectively. Results show that the Nigeria national serial HIV rapid testing algorithm performed very well across the target settings. However, the algorithm's performance in the field was lower than the performance outcomes under a controlled environment in the NRL. There is a need to target testers in the field for routine continuous quality improvement implementation, including refresher trainings as necessary.

Performance of HIV rapid testing algorithm in Nigeria: Findings from a household-based Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS).

The Nigeria AIDS Indicator and Impact Survey (NAIIS), a cross-sectional household survey, was conducted in 2018 with primary objectives to estimate HIV prevalence, HIV-1 incidence, and status of UNAIDS 90-90-90 cascade. We conducted retrospective analysis of the performance of HIV rapid tests and the national HIV testing algorithm used in Nigeria. The national algorithm included Determine HIV-1/2 as test 1 (T1), Unigold HIV-1/2 as test 2 (T2), and StatPak HIV-1/2 as the tie-breaker test (T3). Individuals reactive with T1 and either T2 or T3 were considered HIV-positive. HIV-positive specimens from the algorithm were further confirmed for the survey using supplemental test Geenius HIV-1/2. If Geenius did not confirm HIV-positive status, HIV-1 Western blot was performed. We calculated the concordance between tests and positive predictive value (PPV) of the algorithm on unweighted data. Of 204,930 participants (ages ≥18 months) 5,103 (2.5%) were reactive on T1. Serial testing of T1 reactive specimens with T2 or if needed by tiebreaker T3 identified 2958 (1.44%) persons as HIV-positive. Supplemental testing confirmed 2,800 (95%) as HIV-positive (HIV-1 = 2,767 [98.8%]; HIV-2 = 5 [0.2%]; dual infections = 22 [0.8%]). Concordance between T1 and T2 was 56.6% while PPV of the national algorithm was 94.5%. Our results show high discordant rates and poor PPV of the national algorithm with a false-positive rate of about 5.5% in the NAIIS survey. Considering our findings have major implications for HIV diagnosis in routine HIV testing services, additional evaluation of testing algorithm is warranted in Nigeria.

Preventing mother-to-child transmission of HBV

Hepatitis B virus (HBV) infection is a global public health threat with about 296 million chronic infections worldwide and 1·5 million new infections each year. 1 WHOGlobal progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. Accountability for the global health sector strategies 2016–2021: actions for impact. World Health Organization, Geneva2021 Google Scholar In 2016, WHO developed a global strategy to eliminate hepatitis as a public health threat by 2030, with a goal to reduce incidence by 90% and mortality by 65%. 2 WHOGlobal health sector strategy on viral hepatitis 2016–2021. https://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/Date: 2016 Date accessed: March 13, 2022 Google Scholar Mother-to-child transmission (MTCT) remains a key contributor to HBV incidence globally, 3 Bierhoff M Nelson KE Guo N Jia Y Thio CL Prevention of mother-to-child transmission of hepatitis B virus: protocol for a one-arm, open-label intervention study to estimate the optimal timing of tenofovir in pregnancy. BMJ Open. 2020; 10e038123 Crossref PubMed Scopus (7) Google Scholar and extra interventions beyond the hepatitis B vaccination for children to decrease MTCT are needed. On that basis, the birth dose of hepatitis B vaccine (HepB-BD) combined with hepatitis B immunoglobulin (HBIg) or tenofovir disoproxil fumarate, or both during pregnancy have been proved to effectively prevent MTCT. 4 Funk AL Lu Y Yoshida K et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. Lancet Infect Dis. 2021; 21: 70-84 Summary Full Text Full Text PDF PubMed Scopus (63) Google Scholar However, access to HBIg is an issue in many low-income and middle-income countries (LMICs). Immunoglobulin-free strategy to prevent HBV mother-to-child transmission in Cambodia (TA-PROHM): a single-arm, multicentre, phase 4 trialAn immunoglobulin-free strategy using an HBeAg rapid diagnosis test and alanine aminotransferase-based algorithm to assess eligibility for tenofovir, is effective at preventing MTCT of HBV when tenofovir was initiated at least 4 weeks before birth. Full-Text PDF

Immunoglobulin-free strategy to prevent HBV mother-to-child transmission in Cambodia (TA-PROHM): a single-arm, multicentre, phase 4 trial

Prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is based on administration of vaccine and immunoglobulins (HBIg) to newborns at birth and maternal antiviral prophylaxis for those with an HBV-DNA viral load of at 5·3 log10 IU/mL or more. Many low-income and middle-income countries face difficulty in accessing HBIg and HBV-DNA quantification. The aim of this study was to evaluate the effectiveness of an HBIg-free strategy to prevent MTCT of HBV. TA-PROHM was a single-arm, multicentre, phase 4 trial done in five maternity units in Cambodia. Pregnant women who were positive for hepatitis B surface antigen (HBsAg), aged 18 years or older were included. Women who were HCV or HIV positive, had creatinine clearance of less than 30 mL/min, severe gravid disease, and planned to give birth outside the study sites were excluded. From Oct 4, 2017, to Jan 9, 2019, HBsAg positive pregnant women who tested positive for hepatitis B e antigen (HBeAg) with a rapid diagnostic test were eligible to receive tenofovir disoproxil fumarate. From Jan 9, 2019, women who were HBeAg negative with an alanine aminotransferase concentration of ≥40 IU/L were also eligible to receive tenofovir disoproxil fumarate. Women in the tenofovir disoproxil fumarate eligible group received 300 mg of tenofovir disoproxil fumarate orally once a day from the 24th week of gestation until 6 weeks postpartum. The primary outcome was the overall proportion of infants who were HBsAg positive at 6 months of life, confirmed by positive HBV DNA quantification. For the primary outcome, the proportion (95% CI) of infants with HBsAg at 6 months was stratified according to infant's HBIg status, duration of maternal tenofovir disoproxil fumarate treatment (>4 weeks and ≤4 weeks), and study period (before and after the change in therapeutic algorithm) and was measured in a modified intention-to-treat analysis, which excluded infants lost to follow-up or who were withdrawn before 6 months. The study is registered with ClinicalTrials.gov, NCT02937779. From Oct 4, 2017, to Nov 27, 2020, 21 251 pregnant women were screened for HBsAg, of whom 1194 (6%) were enrolled in the study: 338 (28%) were eligible to receive tenofovir disoproxil fumarate. For the tenofovir disoproxil fumarate eligible group, four (1% [95% CI 0·34-3·20]) of 317 infants had HBV infection at 6 months; in the subgroup of 271 children who did not receive HBIg, four (1% [0·40-3·74]) had HBV infection at 6 months. In absence of HBIg, MTCT HBV transmission occurred in none (0% [0-1·61]) of 227 women who received tenofovir disoproxil fumarate for more than 4 weeks before giving birth and three (8% [1·75-22·47]) of 36 women who received tenofovir disoproxil fumarate for less than 4 weeks. In the tenofovir disoproxil fumarate ineligible group, seven (1% [0·40-2·02]) of 712 infants had HBV infection at 6 months; in the subgroup of 567 children who did not receive HBIg, six (1% [0·39-2·30]) had HBV infection at 6 months. An immunoglobulin-free strategy using an HBeAg rapid diagnosis test and alanine aminotransferase-based algorithm to assess eligibility for tenofovir, is effective at preventing MTCT of HBV when tenofovir was initiated at least 4 weeks before birth. French Agency for Research on AIDS and Viral Hepatitis and Emerging Infectious diseases. For the French translation of the abstract see Supplementary Materials section.

Factors associated with active syphilis among men and women aged 15 years and older in the Zimbabwe Population-based HIV Impact Assessment (2015-2016).

Ulcerative STIs, including syphilis, increase the risk for HIV acquisition and transmission due to the presence of ulcers/chancres that serve as a point-of-entry and exit for HIV. In Zimbabwe, diagnosis of syphilis often occurs in pregnant women who seek ANC services where syphilis testing is offered, and among men and women who seek health care for STIs. Zimbabwe's national syphilis estimates are based on these diagnosed cases, with little information available about the prevalence of untreated syphilis among the general population. This analysis uses data from ZIMPHIA (2015-2016) to describe factors associated with active syphilis among men and women ages 15 years and older. ZIMPHIA collected blood specimens for HIV and syphilis testing from 22,501 consenting individuals (ages 15 years and older). Household HIV testing used the national HIV rapid-testing algorithm with HIV-positive results confirmed at satellite laboratories using Geenius HIV-1/2 rapid test (Bio-rad, Hercules, California, USA). Point-of-care non-Treponemal and Treponemal syphilis testing was performed using Chembio's Dual-Path Platform Syphilis Screen & Confirm Assay. Factors associated with active syphilis were explored using multiple variable, weighted logistic regression and were stratified by gender. The likelihood of active syphilis in HIV-positive females was 3.7 times greater in HIV-positive females than HIV-negative females (aOR: 3.7, 95% CI 2.3-5.9). Among males odds of having active syphilis was 5 times higher among those that engaged in transactional sex than those who did not have sex or transactional sex (aOR: 5.3, 95% CI 1.9-14.7), and 6 times higher if HIV positive versus negative (aOR: 5.9, 95% CI 3.0-12.0). Urban residence, province, education (highest attended), marital status, number of sex partners, consistency of condom use, pregnancy status (females), and circumcision status (males) were not significant in the adjusted model for either females or males. HIV status was found to be the only factor associated with active syphilis in both females and males. Given the persistent link between HIV and active syphilis, it is prudent to link individuals' diagnoses and treatments, as recommended by the WHO. Enhanced integration of STI and HIV services in health delivery points such as ANC, reproductive services, or male circumcision clinics, combined with consistent, targeted outreach to high-risk populations and their partners, may assist the MOHCC to eliminate active syphilis in Zimbabwe.

An Epidemic of Pediatric HIV From Reuse of Infusion Equipment in Pakistan.

From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019. For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression. The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to >1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400). Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested.

Sensitivity and specificity of OraQuick® HIV self-test compared to a 4th generation laboratory reference standard algorithm in urban and rural Zambia

BackgroundHIV self-testing (HIVST) has the potential to increase coverage of HIV testing, but concerns exist about intended users’ ability to correctly perform and interpret tests, especially in poor communities with low literacy rates. We assessed the clinical performance of the 2016 prototype OraQuick® HIV Self-Test in rural and urban communities in Zambia to assess the sensitivity and specificity of the test compared to the national HIV rapid diagnostic test (RDT) algorithm and a laboratory reference standard using 4th generation enzyme immunoassays and HIV RNA detection.MethodsParticipants were recruited from randomly selected rural and urban households and one urban health facility between May 2016 and June 2017. Participants received a brief demonstration of the self-test, and then self-tested without further assistance. The research team re-read the self-test, repeated the self-test, drew blood for the laboratory reference, and conducted RDTs following the national HIV testing algorithm (Determine™ HIV1/2 (Alere) confirmed using Unigold™ HIV1/2 (Trinity Biotech)). Selected participants (N = 85) were videotaped whilst conducting the testing to observe common errors.ResultsInitial piloting showed that written instructions alone were inadequate, and a demonstration of self-test use was required. Of 2,566 self-test users, 2,557 (99.6%) were able to interpret their result. Of participants who were videoed 75/84 (89.3%) completed all steps of the procedure correctly.Agreement between the user-read result and the researcher-read result was 99.1%. Compared to the RDT algorithm, user-conducted HIVST was 94.1% sensitive (95%CI: 90.2–96.7) and 99.7% specific (95%CI: 99.3–99.9). Compared to the laboratory reference, both user-conducted HIVST (sensitivity 87.5%, 95%CI: 82.70–91.3; specificity 99.7%, 95%CI: 99.4–99.9) and the national RDT algorithm (sensitivity 93.4%, 95%CI: 89.7–96.1%; specificity 100% (95%CI: 99.8–100%) had considerably lower sensitivity.ConclusionsSelf-testers in Zambia who used OraQuick® HIV Self-Test achieved reasonable clinical performance compared to the national RDT algorithm. However, sensitivity of the self-test was reduced compared to a laboratory reference standard, as was the national RDT algorithm. In-person demonstration, along with the written manufacturer instructions, was needed to obtain accurate results. Programmes introducing self-care diagnostics should pilot and optimise support materials to ensure they are appropriately adapted to context.

Assessment of the Sedia HIV Self-Test Device: Usability and Performance in the Hands of Untrained Users in Johannesburg, South Africa.

The prevalence of HIV across South Africa places a strain on testing facilities. The use of HIV self-testing (HIVST) devices has been identified as a strategy to ease the burden on these facilities. The usability and performance of the Asante HIV−1/2 Oral Self-Test (Asante) (Sedia Biosciences, Portland OR, USA) device by novice users was assessed and reported on, to inform for the implementation of such devices in South Africa and elsewhere. Convenience sampling was used. Participants used the Asante HIVST device and recorded their interpretation of their results. Participants’ interpretations were compared with those of trained professionals and, thereafter, verified using the rapid diagnostic testing algorithm. Out of the eligible participants, 410 of the 524 (78.2%) were between the ages of 18–35. The usability assessment indicates that 100% of participants used the HIVST device’s information leaflet. However, 19/524 (3.6%) of participants who yielded an invalid result due to critical errors were excluded from the primary efficacy analysis. The average usability score was 98.1%. The sensitivity and specificity results were, 94.7% and 99.8%, respectively. This study shows that the Asante HIV self-test, and similar devices, can be valuable in providing convenient HIV self-testing and immediately available results. To accommodate a greater number of inexperienced users, the instructions may need to be revised.

Factors associated with unawareness of HIV-positive status in urban Ethiopia: Evidence from the Ethiopia population-based HIV impact assessment 2017-2018.

The HIV epidemic in Ethiopia is concentrated in urban areas. Ethiopia conducted a Population-based HIV Impact Assessment (EPHIA) in urban areas between October 2017 and April 2018 to measure the status of the country's response to the epidemic. We conducted field data collection and HIV testing in randomly selected households using the national, rapid testing algorithm with laboratory confirmation of seropositive samples using a supplemental assay. In addition to self-report on HIV diagnosis and treatment, all HIV-positive participants were screened for a set of HIV antiretroviral (ARV) drugs indicative of the first- and second-line regimens. We calculated weighted frequencies and 95% confidence intervals to assess regional variation in participants' level of unawareness of their HIV-positive status (adjusted for ARV status). We interviewed 20,170 survey participants 15-64 years of age, of which 19,136 (95%) were tested for HIV, 614 (3.2%) tested positive, and 119 (21%) of HIV-positive persons were unaware of their HIV status. Progress towards the UNAIDS first 90 target (90% of people living with HIV would be aware of their HIV status by 2020) substantially differed by administrative region of the country. In the bivariate analysis using log binomial regression, three regions (Oromia, Addis Ababa, and Harari), male gender, and young age (15-24 years) were significantly associated with awareness of HIV positive status. In multivariate analysis, the same variables were associated with awareness of HIV-positive status. One-fifth of the HIV-positive urban population were unaware of their HIV-positive status. The number of unaware HIV-positive individuals has a different distribution than the HIV prevalence. National and regional planning and monitoring activities could address this potentially substantial source of undetected HIV infection by increasing HIV testing among young people, men and individuals who do not use condoms.

Opportunities for Closing the Gap in HIV Diagnosis, Treatment, and Viral Load Suppression in Children in Malawi: Results From a 2015-2016 Population-based HIV Impact Assessment Survey.

Control of the pediatric HIV epidemic is hampered by gaps in diagnosis and linkage to effective treatment. The 2015-2016 Malawi Population-based HIV impact assessment data were analyzed to identify gaps in pediatric HIV diagnosis, treatment, and viral load suppression. In half of the surveyed households, children ages ≥18 months to <15 years were tested using the national HIV rapid test algorithm. Children ≤18 months reactive by the initial rapid test underwent HIV total nucleic acid polymerase chain reaction confirmatory testing. Blood from HIV-positive children was tested for viral load (VL) and presence of antiretroviral drugs. HIV diagnosis and antiretroviral treatment (ART) use were defined using guardian-reporting or antiretroviral detection. Of the 6166 children tested, 99 were HIV-positive for a prevalence of 1.5% (95% confidence intervals [CI]: 1.1-1.9) and 8.0% (95% CI: 5.6-10.5) among HIV-exposed children. The prevalence of 1.5% was extrapolated to a national estimate of 119,501 (95% CI: 89,028-149,974) children living with HIV (CLHIV), of whom, 30.7% (95% CI: 20.3-41.1) were previously undiagnosed. Of the 69.3% diagnosed CLHIV, 86.1% (95% CI: 76.8-95.6) were on ART and 57.9% (95% CI: 41.4-74.4) of those on ART had suppressed VL (<1000 HIV RNA copies/mL). Among all CLHIV, irrespective of HIV diagnosis or ART use, 57.7% (95% CI: 45.0-70.5) had unsuppressed VL. Critical gaps in HIV diagnosis in children persist in Malawi. The large proportion of CLHIV with unsuppressed VL reflects gaps in diagnosis and need for more effective first- and second-line ART regimens and adherence interventions.

Time From HIV Infection to Diagnosis in the U.S., 2014–2018

Understanding the role of sociologic, structural, and biomedical factors that influence the length of time from HIV infection to diagnosis and reducing the time from infection to diagnosis are critical for achieving the goals of the Ending the HIV Epidemic initiative. In a retrospective analysis, the length of time from HIV infection to diagnosis and its association with individual- and facility-level attributes are determined. Data reported by December 2019 to the U.S. National HIV Surveillance System for people with HIV diagnosed during 2014-2018 were analyzed during December 2020. A CD4 depletion model was used to estimate the time from HIV infection to diagnosis. During 2018, the median time from HIV infection to diagnosis was shorter for those infections diagnosed using the rapid testing algorithm (30.3 months, 95% CI=25.5, 34.5) than those diagnosed using the recommended (41.0 months, 95% CI=39.5, 42.0), traditional (37.0 months, 95% CI=29.5, 43.5), or other (35.5 months, 95% CI=32.5, 38.0) diagnostic testing algorithms. From 2014 to 2018, the time from HIV infection to diagnosis remained stable overall for all testing methods except for the traditional diagnostic testing algorithm. In multivariate analyses, those more likely to have HIV diagnosed closer to the time of infection were younger, were White, had transmission risk factors of injection drug use or heterosexual contact (for female individuals) or male-to-male sexual contact and injection drug use, or had HIV diagnosed at a correctional or screening facility (p<0.01). Providing access to expanded testing, including rapid testing in nonclinical settings, is likely to result in a decrease in the length of time a person is unaware of their HIV infection and thus reduce onward transmission of HIV infection.

Human Immunodeficiency Virus Infection in Adolescents and Mode of Transmission in Southern Africa: A Multinational Analysis of Population-Based Survey Data.

BackgroundAdolescents aged 10–19 years living with human immunodeficiency virus (HIV) (ALHIV), both perinatally infected adolescents (APHIV) and behaviorally infected adolescents (ABHIV), are a growing population with distinct care needs. We characterized the epidemiology of HIV in adolescents included in Population-based HIV Impact Assessments (2015–2017) in Zimbabwe, Malawi, Zambia, Eswatini, and Lesotho.MethodsAdolescents were tested for HIV using national rapid testing algorithms. Viral load (VL) suppression (VLS) was defined as VL <1000 copies/mL, and undetectable VL (UVL) as VL <50 copies/mL. Recent infection (within 6 months) was measured using a limiting antigen avidity assay, excluding adolescents with VLS or with detectable antiretrovirals (ARVs) in blood. To determine the most likely mode of infection, we used a risk algorithm incorporating recency, maternal HIV and vital status, history of sexual activity, and age at diagnosis.ResultsHIV prevalence ranged from 1.6% in Zambia to 4.8% in Eswatini. Of 707 ALHIV, 60.9% (95% confidence interval, 55.3%–66.6%) had HIV previously diagnosed, and 47.1% (41.9%–52.3%) had VLS. Our algorithm estimated that 72.6% of ALHIV (485 of 707) were APHIV, with HIV diagnosed previously in 69.5% of APHIV and 39.4% of ABHIV, and with 65.3% of APHIV and 33.5% of ABHIV receiving ARV treatment. Only 67.2% of APHIV and 60.5% of ABHIV receiving ARVs had UVL.ConclusionsThese findings suggest that two-thirds of ALHIV were perinatally infected, with many unaware of their status. The low prevalence of VLS and UVL in those receiving treatment raises concerns around treatment effectiveness. Expansion of opportunities for HIV diagnoses and the optimization of treatment are imperative.

Use of Trained Non-Medical Staff to Improve Access to HIV Testing Services in Africa: Implementation of the World Health Organization Opt-out Approach in Cameroon.

Background:The Joint United Nations Programme on HIV/AIDS (UNAIDS) in 2019 estimated that 450,000 to 50,000 people in Cameroon were living with HIV, yet only 79% knew their HIV status which is far from the 90% target for 2020. To address this situation, Cameroon adopted the “Opt-out” strategy of the World Health Organization (WHO) and use of trained non-medical cadre (psychosocial agents) to reach out to more people with HIV testing services (HTS). This describes the implementation and outcomes of this strategy by reviewing the activity of a typical day in the Yaoundé Central Hospital (YCH) in Cameroon.Methods:HTS were offered to hospitalized and ambulatory patients (including their companions) in different departments of the YCH. Following screening for recent HIV testing, those with unknown HIV status that gave consent or did not explicitly refuse testing (as per the “Opt-out Strategy”), were counseled and tested for HIV. Testing followed the “National HIV Rapid Testing Algorithm” using rapid diagnostic test kits. Results were either positive, negative or indeterminate. Patients with positive HIV results were linked to the Care and Treatment Center for treatment initiation.Results:Of the 350 patients screened and offered HTS using non-medical cadre (psychosocial agents), 193 (55.1%) were hospitalized and 157 (44.9%) came for outpatient visits. The age of participants ranged from 14 to 92 years and the yield of HIV testing in the sample population was 5.1% (6.2% for hospitalized patients and 3.8% for outpatient clinics). Statistics revealed that five HIV-positive patients had never been offered HTS before the study. The study revealed that HTS acceptance rate among hospitalized patients was 69.6% and that all new positive patients started antiretroviral treatment on the same day.Conclusion and Global Health Implications:It is feasible to use trained non-medical staff for HIV testing services (HTS). Task-shifting by using trained psychosocial agents can help in case identification and linkage to HIV treatment services.

Evaluation of Rapid Testing Algorithms for Venue-based Anonymous HIV Testing among Non-HIV-Positive Men Who Have Sex with Men, National HIV Behavioral Surveillance (NHBS), 2017

HIV rapid testing algorithms (RTAs) using any two orthogonal rapid tests (RTs) allow for on-site confirmation of infection. RTs vary in performance characteristics therefore the selection of RTs in an algorithm may affect identification of infection, particularly if acute. National HIV Behavioral Surveillance (NHBS) assessed RTAs among men who have sex with men recruited using anonymous venue-based sampling. Different algorithms were evaluated among participants who self-reported never having received a positive HIV test result prior to the interview. NHBS project areas performed sequential or parallel RTs using whole blood. Participants with at least one reactive RT were offered anonymous linkage to care and provided a dried blood spot (DBS) for testing at CDC. Discordant results (RT-1 reactive/RT-2 non-reactive) were tested at CDC with lab protocols modified for DBS. DBS were also tested for HIV-1 RNA (VL) and antiretroviral (ARV) drug levels. Of 6500 RTAs, 238 were RT-1 reactive; of those, 97.1% (231/238) had concordant results (RT-1/RT-2 reactive) and 2.9% (7/238) had discordant results. Five DBS associated with discordant results were available for confirmation at CDC. Four had non-reactive confirmatory test results that implied RT-1 false reactivity; one had ambiguous confirmatory test results which was non-reactive in further testing. Regardless of order and type of RT used, RTAs demonstrated high concordant results in the population surveyed. Additional laboratory testing on DBS following discordant results confirmed no infection. Implementing RTAs in the context of anonymous venue-based HIV testing could be an option when laboratory follow-up is not practicable.

Rapid Testing Algorithm Performance in a Low-Prevalence Environment.

The performance of a statewide HIV rapid test algorithm (RTA) in a low-prevalence setting (0.71%) was examined for 3 years. An initial rapid screening by HIV-1/2 Ag/Ab Combo test (RT#1) with Ab verification using a second, different rapid test (RT#2) was conducted. Clinic referral was immediate for antigen-only-positive screens. Antibody-positive screens were confirmed by RT#2. Specimens were collected following discordant RTA results (initially Ab-POS by RT#1, but negative on RT#2) and tested in accordance with the current Centers for Disease Control and Prevention/Association of Public Health Laboratories-based HIV diagnostic algorithm supplemented by a quantitative viral load whenever possible. Of 310,785 tests performed, 2400 preliminary positive screens were identified; 2191 (91.8%) confirmed by RT#2. Of 13 Determine Combo AG-POS results identified, only 1 confirmed positive. Of the remaining 196 discordant results, 182 (92.9%) were uninfected, including 13 with AG-POS/AB-POS results. Of 14 true positives (7.1%) identified after discordant RTA results, the average quantitative HIV-1 viral load was 277,385 copies/mL, but 5 (35.7%) of 14 had viral loads <1000 copies/mL. Among the 2191 "presumptive positive" by RTA, 3 false-positive (FP) RTAs were reported (both rapid tests having positive results, while the HIV-1/2 Ag/Ab assay and quantitative HIV-1 viral load showed negative results). The RTA was effective in predicting true-positive HIV test results and facilitating linkage to care. Discordant results were infrequent. Fingerstick DC Ag detection identified a single early infection. Many discordant cases that were subsequently positive were associated with viral loads <1000 copies/mL.

Clinic-based evaluation study of the diagnostic accuracy of a dual rapid test for the screening of HIV and syphilis in pregnant women in Nigeria.

BackgroundScreening pregnant women for HIV and syphilis is recommended by WHO in order to reduce mother-to-child transmission. We evaluated the field performance, feasibility, and acceptability of a dual rapid diagnostic test (RDT) for HIV and syphilis test in antenatal clinic settings in Nigeria.Methods and findingsParticipants were recruited at 12 antenatal clinic sites in three states of Nigeria. All consenting individuals were tested according to the national HIV testing algorithm, as well as a dual RDT, the SD BIOLINE HIV/Syphilis Duo Test (Alere, USA), in the clinic. To determine sensitivity, specificity and concordance, whole blood samples were obtained for repeat RDT performance in the laboratory, as well as reference tests for HIV and syphilis. Dual test acceptability and operational characteristics were assessed among participants and clinic staff.The prevalence of HIV among the 4,551 enrollees was 3.0% (138/4551) using the national clinic-based HIV testing algorithm. Positive and negative percent agreement of the HIV component of the dual RDT were 100.0% (95% CI 99.7–100.0) and 99.9% (95% CI 99.7–100.0) respectively, when compared with the national rapid testing algorithm. The prevalence of syphilis, using TPHA as the reference test, was low at 0.09% (4/4550). The sensitivity of the syphilis component of the dual RDT could not be calculated as no positive results were observed for patients that were positive for syphilis by TPHA. Each of the only four TPHA-positive specimens had RPR titers of 1:1 (neat), indicative of non-active syphilis. The specificity of the syphilis component of the dual RDT was 99.9% (95% CI 99.8–100.0).The dual RDT received favorable feasibility ratings among antenatal care clinic staff. Acceptability among study participants was high with most women reporting preference for rapid dual HIV/syphilis testing.ConclusionsThe SD BIOLINE HIV/Syphilis Duo Test showed a high overall diagnostic accuracy for HIV and a high specificity for syphilis diagnosis in antenatal clinic settings. This study adds to a growing body of evidence that supports the clinic-based use of dual tests for HIV and syphilis among pregnant women.