External quality assessment to support the WHO ProSPeRo study for the evaluation of two dual HIV/syphilis point-of-care tests in seven countries.

BACKGROUND: Sexually transmitted infections (STIs) such as syphilis and HIV remain to be a significant public health issue worldwide. Dual rapid point-of-care tests (POCTs) have shown promise for detecting antibodies to HIV and syphilis but have not been fully evaluated in the field. Our study supported the WHO ProSPeRo study on Sexually Transmitted Infection Point-of-Care Testing (STI POCT) by providing external quality assessment (EQA) for HIV and syphilis testing in reference laboratories and their associated clinical sites in seven countries. METHODS: HIV/syphilis serum liquid and dried tube specimen (DTS) panels were prepared by CDC. Liquid panels were distributed to the reference laboratories for three rounds of testing using commercially and locally available laboratory-based serological tests. DTS panels were sent to the clinical testing sites for 8 rounds of POC testing using the Abbott SD BIOLINE HIV/Syphilis Duo test (hereafter referred to as SD BIOLINE) and the Chembio Dual Path Platform (DPP) HIV-Syphilis assay. EQA panels were tested at CDC using the Rapid Plasma Reagin (RPR) test and the Treponema pallidum Particle Agglutination assay (TP-PA) for syphilis antibodies. Genetic Systems HIV-1/HIV-2 Plus O EIA, Geenius HIV Supplemental Assay and the Oraquick Advance HIV test were used to detect HIV antibodies in the EQA panels. Results from the reference laboratories and POCT sites were compared to those obtained at the CDC and a percentage agreement was calculated. RESULTS: Qualitative RPR and TP-PA performed at the reference laboratories demonstrated 95.4-100% agreement with CDC results while quantitative RPR and TP-PA tests demonstrated 87.7% and 89.2% agreement, respectively. A 93.8% concordance rate was observed for qualitative HIV testing in laboratories. EQA testing at clinical sites using dual tests showed 98.7% and 99.1% agreement for detection of HIV antibodies and eight out of 10 sites had > 95.8% agreement for syphilis testing. However, two clinical sites showed only 65.0-66.7% agreement for SD BIOLINE and 84.0-86.7% for DPP, respectively, for syphilis testing. CONCLUSIONS: Overall, laboratories demonstrated high EQA performance in this study. Both HIV/syphilis POCTs gave expected results in the clinic-based evaluations using DTS. However, testing errors were identified in a few testing sites suggesting the necessity for continuous training and monitoring the quality of POC testing.

Recent HIV-1 infection in Israel 2017-2021: Evaluation of geenius and HIV-1/2 combo assays for identifying recent infection detected by Sedia assay and assessment of factors related to recent infection: Recent HIV-1 infection in Israel.

BACKGROUND: Estimating HIV-1 recency of infection for incidence and local outbreaks detection usually involves specifically designed assays. Here, we established an approach to identify recent infections, estimate their rate, and assess potential risk factors. METHODS: Randomly selected HIV-1 positive samples (n = 382) collected in 2017-2021 were tested by Sedia and compared to the results of Geenius recency algorithm and the S/CO values of the HIV-1/2 Combo assay. Using Geenius and Combo recency verdict, we assessed all cases diagnosed in 2017-2021. Related factors were further assessed. RESULTS: While Geenius and Combo had a sensitivity of 65.9 % and 89.30 %, respectively, and specificity of 96 % and 90 %, respectively, compared to Sedia, higher concordance (97.2 %) and kappa (>0.9) were observed when the verdict of both assays together was compared to Sedia. Using this approach, 15.3 % (238/1548) of individuals diagnosed in 2017-2021 were defined as recently infected. In multivariate analysis, recent diagnosis was mainly associated with men who have sex with men (MSM) and with birthplace in Israel, Western/Central Europe, or North America. CONCLUSIONS: Only 15.3 % of infections in 2017-2021, mainly in MSM and Israeli/Western countries-born individuals, were diagnosed early. Regular diagnostic assays have a potential to identify and monitor trends in recent infections.

Modeling the future of HIV in Turkey: Cost-effectiveness analysis of improving testing and diagnosis.

AIMS: This study aimed to determine HIV incidence and prevalence in Turkey and to estimate the cost-effectiveness of improving testing and diagnosis in the next 20 years. BACKGROUND: HIV incidence in Turkey has been rapidly increasing in the last decade with a particularly high rate of infection for younger populations, which underscores the urgent need for a robust prevention program and improved testing capacity for HIV. METHODS: We developed a dynamic compartmental model of HIV transmission and progression among the Turkish population aged 15-64 and assessed the effect of improving testing and diagnosis. The model generated the number of new HIV cases by transmission risk and CD4 level, HIV diagnoses, HIV prevalence, continuum of care, the number of HIV-related deaths, and the expected number of infections prevented from 2020 to 2040. We also explored the cost impact of HIV and the cost-effectiveness of improving testing and diagnosis. RESULTS: Under the base case scenario, the model estimated an HIV incidence of 13,462 cases in 2020, with 63% undiagnosed. The number of infections was estimated to increase by 27% by 2040, with HIV incidence in 2040 reaching 376,889 and HIV prevalence 2,414,965 cases. Improving testing and diagnosis to 50%, 70%, and 90%, would prevent 782,789, 2,059,399, and 2,336,564 infections-32%, 85%, and 97% reduction in 20 years, respectively. Improved testing and diagnosis would reduce spending between $1.8 and $8.8 billion. CONCLUSIONS: In the case of no improvement in the current continuum of care, HIV incidence and prevalence will significantly increase over the next 20 years, placing a significant burden on the Turkish healthcare system. However, improving testing and diagnosis could substantially reduce the number of infections, ameliorating the public health and disease burden aspects.

Assessment of the Proportion of Recent HIV-1 Infections in Newly-Diagnosed Cases in Ghana.

Accurate monitoring of epidemics is a key strategy for controlling human immunodeficiency virus type-1 (HIV-1) infection. To delineate the characteristics of newly diagnosed cases of HIV-1 infection, we assessed the proportion of recent HIV-1 infections using a recent infection-testing algorithm (RITA). In 2015, 248 cases were newly diagnosed with HIV infection at the Regional Hospital Koforidua, Ghana. Of these, 234 cases (94.4%) were infected with HIV-1 only, four (1.6%) were infected with HIV-2 only, and 10 (4.0%) were co-infected with HIV-1 and HIV-2. All HIV-1 single-seropositive samples were used in the HIV-1 LAg avidity assay for RITA. Our analysis revealed that 18 cases (7.7%) were recently infected, indicating that early diagnosis was not achieved in Ghana. This is the first report to assess the proportion of recent infections in Ghana using a biomarker approach. The accumulation of these data will contribute to the accurate estimation of HIV-1 incidence and prevalence in Ghana.

Neurocognitive evaluation using the International HIV Dementia Scale (IHDS) and Montreal Cognitive Assessment Test (MoCA) in an HIV-2 population.

OBJECTIVES: We aimed to characterize neurocognitive impairment (NI) in an HIV-2 population using an observational cross-sectional study in four Portuguese hospitals. METHODS: Adult HIV-2-infected patients were included. Montreal Cognitive Assessment Test (MoCA) and International HIV Dementia Scale (IHDS) scales were applied for screening of NI. Patient Health Questionnaire-9 (PHQ-9) and Instrumental Activities of Daily Living (IADL) scales were used for assessment of depression and functionality. A multivariate analysis was performed to assess for risk factors for NI. RESULTS: Eighty-one patients were included, 50.6% of African origin (n = 41) and 49.4% of Portuguese origin (n = 40). The MoCA scale showed alterations in 81.5% of patients (100% of migrants vs. 62.5% of non-migrants, P < 0.001) and the IHDS scale showed alterations in 42%. Both scales were altered simultaneously in 35.8%. Variables independently associated with NI were age [odds ratio (OR) = 0.885] and migrant status (OR = 9.150). CONCLUSIONS: Neurocognitive impairment (both scales altered) was present in 35.8%, which is comparable to what is described for HIV-1. The MoCA performed worse in the migrant population and might not be applicable in this setting.

[Ivory-Coast: Textbooks Misinform on HIV]. / Côte d'Ivoire : la désinformation des manuels scolaires sur l'infection à VIH.

Schools are considered as one of the most effective vectors for education on sexually transmitted diseases among young people. We report here the results of a study of HIV infection as presented in school textbooks in Ivory Coast, conducted in June 2018 as part of the development of a communication strategy to increase demand for HIV infection testing, especially among young people. Surprisingly, even though the textbooks studied were published between 2007 and 2017, almost all of them stated that HIV infection leads to death, with no mention of the existence of treatments that make it possible to live in good health. Some textbooks even stated that no treatment is available. These findings highlight one cause - perhaps major - for the reluctance of young people to get tested. The misrepresentation of HIV infection, reinforced by education, hampers incentive campaigns for HIV testing, for which the best argument is that awareness of a positive HIV status makes it possible to benefit from treatment. The present study included textbooks from the French educational program, used throughout French-speaking Africa, and from the Ivory Coast program. It would be interesting to conduct a similar study in other French-speaking and English-speaking African countries. Adapting the presentation of HIV in school textbooks to reflect the current situation in the fight against HIV infection should be a priority.

L'éducation scolaire est connue comme l'un des vecteurs les plus efficaces d'éducation sur les maladies sexuellement transmissibles chez les jeunes. Nous rapportons ici les résultats d'une étude de la présentation de l'infection à VIH dans les manuels scolaires en Côte d'Ivoire. De façon surprenante, bien qu'ils aient été imprimés entre 2007 et 2017, ces manuels affirment dans leur quasi-totalité que le VIH conduit à la mort, sans mentionner l'existence de traitements qui permettent de vivre en bonne santé, voire pour certains en affirmant qu'il n'existe pas de traitement. Ceci met en lumière une cause, peut-être majeure, de la réticence des jeunes à se faire dépister. La représentation erronée de l'infection à VIH renforcée par l'enseignement entrave les campagnes d'incitation au passage du test de dépistage, le meilleur argument pour celui-ci étant que connaître son statut positif permet de bénéficier des traitements. Certains des livres étudiés sont utilisés dans toute l'Afrique francophone. Il serait intéressant de mener une étude similaire dans d'autres pays d'Afrique francophone et anglophone. Vérifier le contenu scientifique et adapter le discours des manuels scolaires sur le VIH à la situation actuelle de la lutte contre l'infection devraient être une urgence.

Field performance of the INSTI HIV-1/-2 antibody test in two South African antenatal clinics.

This was a prospective study that assessed field performance of the INSTI HIV-1/-2 antibody test (INSTI test) in two antenatal clinics in South Africa (SA). INSTI test was evaluated against rapid tests used at these clinics, and pooled nucleic acid amplification testing (NAAT) performed for individuals with negative rapid tests. Three hundred and eighty-six pregnant women were enrolled; 334 (86.5%) with negative results on the screening rapid test, and 52 (13.5%; 95% confidence interval [CI]: 10.2-17.3%) with positive results on screening and confirmatory rapid tests. INSTI test yielded the same results as other rapid tests in all participants, thus showing a 100% sensitivity (95% CI: 93.2-100.0%) and specificity (95% CI: 98.9-100.0%). Pooled NAAT was performed for 290 participants who had negative rapid tests, and yielded negative results in all pools. These data show excellent field performance of the INSTI test, and highlight that this test can be implementedat SA clinics.

A cheap and open HIV viral load technique applicable in routine analysis in a resource limited setting with a wide HIV genetic diversity.

BACKGROUND: HIV infection in Cameroon is characterized by a great viral diversity with all HIV-1 groups (M, N, O, and P) and HIV-2 in circulation. HIV group determination is very important if tailored viral load analysis and treatments are to be applied. In our laboratory, HIV viral load is carried out using two platforms; Biocentric and Abbott depending on the HIV group identified. Biocentric which quantifies HIV-1 group M is a cheap and open system useful in resource limited settings. The objective of this study was to compare the viral load analyses of serologically group-indeterminate HIV samples using the two platforms with the view of reducing cost. METHODS: Consecutive samples received between March and May 2014, and between August and September 2014 in our laboratory for HIV viral load analysis were included. All these samples were analyzed for their HIV groups using an in-house ELISA serotyping test. All HIV-1 group M samples were quantified using the Biocentric test while all other known atypical samples (HIV-1 groups N, O and P) were analyzed using the Abbott technique. HIV group-indeterminate samples (by serotyping) were quantified with both techniques. RESULTS: Among the 6355 plasma samples received, HIV-1 group M was identified in 6026 (94.82%) cases; HIV-1 group O, in 20 (0.31%); HIV-1 group M + O, in 3 (0.05%) and HIV-2, in 3 (0.05%) case. HIV-group indeterminate samples represented about 4.76% (303/6355) and only 231 of them were available for analysis by Abbott Real-Time HIV-1 and Generic HIV Viral Load techniques. Results showed that 188 (81.39%) samples had undetectable viral load in both techniques. All the detectable samples showed high viral load, with a mean of 4.5 log copies/ml (range 2.1-6.5) for Abbott Real-Time and 4.5 log copies/ml (range 2-6.4) for Generic HIV Viral Load. The mean viral load difference between the two techniques was 0.03 log10 copies/ml and a good correlation was obtained (r 2 = 0.89; P < 0.001). CONCLUSION: Our results suggest that cheaper and open techniques such as Biocentric could be useful alternatives for HIV viral load follow-up quantification in resource limited settings like Cameroon; even with its high viral diversity.

HIV testing week 2015: lowering barriers for HIV testing among high-risk groups in Amsterdam.

BACKGROUND: Evaluation of the HIV Testing Week (HTW) 2015 in Amsterdam: the number of (positive) tested persons, characteristics and testing history of the tested population, the differences in attendance per location and the healthcare workers' experiences and opinions concerning the HTW. METHODS: The HTW took place from 28 November till 4 December 2015. Anonymous HIV rapid testing (INSTI™ HIV1/HIV2 Ab test or Determine™ HIV-1/2 Ag/Ab test) was offered free of charge at four hospitals, 12 general practitioner (GP) clinics, a sexually transmitted infections (STI) clinic, a laboratory, sites of a community-based organisation, and at outreach locations. Home-based testing (OraQuick® In-Home HIV Test) was offered online. The focus was to motivate two groups to test: men who have sex with men (MSM) and non-Western migrants. Questionnaires regarding participant's characteristics and HIV testing history were collected. Also healthcare workers were asked to complete a questionnaire evaluating the HTW. RESULTS: In total, 1231 participants were tested. With three positive HIV tests, the detection rate was 0.3% (95%CI 0.26-0.37). Of all participants, 24.7% (304/1231) were MSM. Respectively, 22.3% (275/1231) and 15.7% (193/1231) were first- and second-generation migrants from a non-Western country. Altogether, 56.7% (698/1231) of participants belonged to one of the targeted risk groups. For 32.7% (402/1231) of participants, it was the first time they received testing, and 35.1% (432/1231) were tested more than 1 year ago. Among MSM 13.2% were tested for the first time, among first- and second-generation non-Western migrants this percentage was significantly higher at 27.2% and 33.5% respectively (p < 0.01). The number of tested participants per location varied widely, especially between GP clinics (range 3-63). Healthcare workers were positive about the HTW: about half (46.2%) stated they would more readily offer an HIV test following their experience with the HTW. CONCLUSIONS: This was the first time the Amsterdam HTW was organised on such a large scale. The majority of the tested population belonged to one of the targeted risk groups and received testing either for the first time or for the first time in over a year. It is important to further build upon the experiences of the HTW and offer free of charge low-threshold HIV testing more structurally. An evaluation of cost-effectiveness is also warranted for future editions of the HTW.

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.

BACKGROUND: Updated 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. OBJECTIVES: The 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 DESIGN: The 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. RESULTS: A 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. CONCLUSIONS: Both 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.

[Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription]. / Médicaments non antirétroviraux chez les personnes vivant avec le VIH sous traitement antirétroviral au Sénégal : coûts et facteurs associés à la prescription.

BACKGROUND: In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. METHODS: We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. RESULTS: The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m2 and 93 cells/µL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. CONCLUSION: Non-antiretroviral drugs are frequently prescribed to people living with HIV in developing countries; mainly those infected with HIV-1 and those at an advanced clinical stage. Their costs can be a barrier to appropriate care and necessary efforts must made to make them available. However, early initiation of antiretroviral therapy and the registration of some non-antiretroviral drugs on the list of essential drugs, as well as social protection systems, should reduce their use and costs.

Assessment of the Cavidi ExaVir Load Assay for Monitoring Plasma Viral Load in HIV-2-Infected Patients.

HIV plasma viral load is an established marker of disease progression and of response to antiretroviral therapy, but currently there is no commercial assay validated for the quantification of viral load in HIV-2-infected individuals. We sought to make the first clinical evaluation of Cavidi ExaVir Load (version 3) in HIV-2-infected patients. Samples were collected from a total of 102 individuals living in Cape Verde, and the HIV-2 viral load was quantified by both ExaVir Load and a reference in-house real-time quantitative PCR (qPCR) used in Portugal in 91 samples. The associations between viral load and clinical prognostic variables (CD4+ T cell counts and antiretroviral therapy status) were similar for measurements obtained using ExaVir Load and qPCR. There was no difference between the two methods in the capacity to discriminate between nonquantifiable and quantifiable HIV-2 in the plasma. In samples with an HIV-2 viral load quantifiable by both methods (n = 27), the measurements were highly correlated (Pearson r = 0.908), but the ExaVir Load values were systematically higher relative to those determined by qPCR (median difference, 0.942 log10 copies/ml). A regression model was derived that enables the conversion of ExaVir Load results to those that would have been obtained by the reference qPCR. In conclusion, ExaVir Load version 3 is a reliable commercial assay to measure viral load in HIV-2-infected patients and therefore a valuable alternative to the in-house assays in current use.

Acute infections, cost and time to reporting of HIV test results in three U.S. State Public Health Laboratories.

OBJECTIVE: In three U.S. State Public Health Laboratories (PHLs) using a fourth-generation immunoassay (IA), an HIV-1/HIV-2 differentiation antibody IA and a nucleic acid test (NAT), we characterized the yield and time to reporting of acute infections, and cost per positive specimen. METHODS: Routine HIV testing data were collected from July 1, 2012-June 30, 2013 for Massachusetts and Maryland PHLs, and from November 27, 2012-June 30, 2013 for Michigan PHL. Massachusetts and Michigan used fourth-generation and differentiation IAs with NAT conducted by a referral laboratory. In Maryland, fourth-generation IA repeatedly reactive specimens were followed by a Western blot (WB), and those with negative or indeterminate results were tested with a differentiation IA and HIV-1 NAT, and if positive by NAT, confirmed by a different HIV-1 NAT. Specimens from WB-positive persons at risk for HIV-2 were tested with a differentiation IA and, if positive, with an HIV-2 WB and/or differential HIV-1/HIV-2 proviral DNA polymerase chain reaction. RESULTS: Among 7914 specimens from Massachusetts PHL, 6069 from Michigan PHL, and 36,266 from Maryland PHL, 0.10%, 0.02% and 0.05% acute infections were identified, respectively. Massachusetts and Maryland PHLs each had 1 HIV-2 positive specimen. The median time from specimen receipt to laboratory reporting of results for acute infections at Massachusetts, Michigan and Maryland PHLs was 8, 11, and 7 days respectively. The laboratory cost per HIV positive specimen was $336 (Massachusetts), $263 (Michigan) and $210 (Maryland). CONCLUSIONS: Acute and established infections were found by PHLs using fourth-generation IA in conjunction with antibody tests and NAT. Time to reporting of acute HIV test results to clients was suboptimal, and needs to be streamlined to expedite treatment and interrupt transmission.

The performance of reverse transcriptase assay for the estimation of the plasma viral load in HIV-1 and HIV-2 infections.

Viral load testing for human immunodeficiency virus 1 (HIV-1) in resource-poor settings continues to be a challenge. Although antiretroviral therapy (ART) is being made available in developing countries, monitoring of viral load is not being done on a regular basis. The purpose of this study was to assess the utility of Cavidi version 3.0, which measures the plasma reverse transcriptase (RT) activity and compare its performance with molecular HIV viral load assays. In all, 125 HIV-1 and 13 HIV-2 positive samples were analyzed. The overall sensitivity of the assay was 86.8% and 94.1% for viral load >1000 copies/ml measured by Qiagen Artus HIV-1 RG RT PCR and Abbott RealTime HIV-1 PCR assays, respectively. Compared with the routine molecular viral load assays, Cavidi version 3.0 is inexpensive, user-friendly, the expenditure on infrastructure is minimal, and it can be used for monitoring of both HIV types.

Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand.

BACKGROUND: Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick) in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs. METHODS: The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT) every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive. RESULTS: We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5%) were confirmed HIV-infected, 10 (2.2%) HIV-uninfected, and one (0.2%) had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days) than participants receiving placebo (16.8 days) (p = 0.02) and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04). DISCUSSION: The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119106.

Estimating the cost-effectiveness of pre-exposure prophylaxis to reduce HIV-1 and HSV-2 incidence in HIV-serodiscordant couples in South Africa.

OBJECTIVE: To estimate the cost-effectiveness of daily oral tenofovir-based PrEP, with a protective effect against HSV-2 as well as HIV-1, among HIV-1 serodiscordant couples in South Africa. METHODS: We incorporated HSV-2 acquisition, transmission, and interaction with HIV-1 into a microsimulation model of heterosexual HIV-1 serodiscordant couples in South Africa, with use of PrEP for the HIV-1 uninfected partner prior to ART initiation for the HIV-1 1infected partner, and for one year thereafter. RESULTS: We estimate the cost per disability-adjusted life-year (DALY) averted for two scenarios, one in which PrEP has no effect on reducing HSV-2 acquisition, and one in which there is a 33% reduction. After a twenty-year intervention, the cost per DALY averted is estimated to be $10,383 and $9,757, respectively--a 6% reduction, given the additional benefit of reduced HSV-2 acquisition. If all couples are discordant for both HIV-1 and HSV-2, the cost per DALY averted falls to $1,445, which shows that the impact is limited by HSV-2 concordance in couples. CONCLUSION: After a 20-year PrEP intervention, the cost per DALY averted with a reduction in HSV-2 is estimated to be modestly lower than without any effect, providing an increase of health benefits in addition to HIV-1 prevention at no extra cost. The small degree of the effect is in part due to a high prevalence of HSV-2 infection in HIV-1 serodiscordant couples in South Africa.

Costs and outcomes of laboratory diagnostic algorithms for the detection of HIV.

BACKGROUND: An alternative HIV testing algorithm, designed to improve the detection of acute and early infections and differentiate between HIV-1 and HIV-2 antibodies, has been developed by the Centers for Disease Control and Prevention and the Association of Public Health Laboratories. While it promises greater sensitivity, it also raises concerns about costs. OBJECTIVE: We sought to compare the most commonly used algorithm which was developed in 1989, a third-generation (3G) immunoassay (IA) and Western blot confirmatory test, to a newer algorithm. The new algorithm includes either a 3G or a fourth-generation (4G) initial IA, followed by confirmatory testing with a HIV-1/HIV-2 differentiation IA and, if needed, a nucleic acid amplification test (NAT). STUDY DESIGN: We conducted an analysis of HIV testing costs from the perspective of the laboratory, and classified costs according to IA testing volume. We developed a decision analytic model, populated with cost data from 17 laboratories and published assay performance data, to compare the cost-effectiveness of the testing algorithms for a cohort of 30,000 specimens with a 1% HIV prevalence and 0.1% acute HIV infection prevalence. RESULTS: Costs were lower in high-volume laboratories regardless of testing algorithm. For specimens confirmed positive for HIV antibody, the alternative algorithm (IA, Multispot) was less costly than the current algorithm (IA, WB); however, there was wide variation in reported testing costs. For our cohort, the alternative algorithm initiated with a 3G IA and 4G IA identified 15 and 25 more HIV infections, respectively, than the 1989 algorithm. In medium-volume laboratories, the 1989 algorithm was more costly and less effective than the alternative algorithm with a 3G IA; in high-volume laboratories, the alternative algorithm with 3G IA costs $162 more per infection detected. The alternative algorithm with 4G instead of 3G incurred an additional cost of $14,400 and $4865 in medium- and high-volume labs, respectively. DISCUSSION: HIV testing costs varied with IA testing volumes. The additional cost of 4G over 3G IA might be justified by the additional cases of HIV detected and transmissions averted due to earlier detection. CONCLUSION: The alternative HIV testing algorithm compares favorably to the 1989 algorithm in terms of cost and effectiveness.

Automatic oral fluid-based HIV testing in HIV screening programmes: automatic for the people.

OBJECTIVES: UK guidelines recommend routine HIV testing in general clinical settings when the local HIV prevalence is > 0.2%. During pilot programmes evaluating the guidelines, we used laboratory-based testing of oral fluid from patients accepting tests. Samples (n = 3721) were tested manually using the Bio-Rad Genscreen Ultra HIV Ag-Ab test (Bio-Rad Laboratories Ltd, Hemel Hempstead, UK). This was a methodologically robust method, but handling of samples was labour intensive. We performed a validation study to ascertain whether automation of oral fluid HIV testing using the fourth-generation HIV test on the Abbott Architect (Abbott Diagnostics, Maidenhead, UK) platform was possible. METHODS: Oral fluid was collected from 143 patients (56 known HIV-positive volunteers and 87 others having contemporaneous HIV serological tests) using the Oracol+ device (Malvern Medicals, Worcester, UK). Samples were tested concurrently: manually using the Genscreen Ultra test and automatically on the Abbott Architect. RESULTS: For oral fluid, the level of agreement of results between the platforms was 100%. All results agreed with HIV serology. The use of the Oracol+ device produced high-quality samples. Subsequent field use of the test has shown a specificity of 99.97% after nearly 3000 tests. CONCLUSIONS: Laboratory-based HIV testing of oral fluid requires less training of local staff, with fewer demands on clinical time and space than near-patient testing. It is acceptable to patients. The validation exercise and subsequent clinical experience support automation, with test performance preserved. Automation reduces laboratory workload and speeds up the release of results. Automated oral fluid testing is thus a viable option for large-scale HIV screening programmes.

Dating phylogenies with sequentially sampled tips.

We develop a Bayesian Markov chain Monte Carlo (MCMC) algorithm for estimating divergence times using sequentially sampled molecular sequences. This type of data is commonly collected during viral epidemics and is sometimes available from different species in ancient DNA studies. We derive the distribution of ages of nodes in the tree under a birth-death-sequential-sampling (BDSS) model and use it as the prior for divergence times in the dating analysis. We implement the prior in the MCMCtree program in the PAML package for divergence dating. The BDSS prior is very flexible and, with different parameters, can generate trees of very different shapes, suitable for examining the sensitivity of posterior time estimates. We apply the method to a data set of SIV/HIV-2 genes in comparison with a likelihood-based dating method, and to a data set of influenza H1 genes from different hosts in comparison with the Bayesian program BEAST. We examined the impact of tree topology on time estimates and suggest that multifurcating consensus trees should be avoided in dating analysis. We found posterior time estimates for old nodes to be sensitive to the priors on times and rates and suggest that previous Bayesian dating studies may have produced overconfident estimates.