Sensitivity of Five Rapid HIV Tests on Oral Fluid or Finger-Stick Whole Blood: A Real-Time Comparison in a Healthcare Setting

Background

Health authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known.

Methods and Findings

200 adults with documented HIV-1 (n = 194) or HIV-2 infection (n = 6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2® was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2®, Determine HIV 1–2®, Determine® HIV-1/2 Ag/Ab Combo® and INSTI HIV-1/HIV-2®. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (p<0.0001). OraQuick was less sensitive on OF than on FSB (p = 0.008). Among the six patients with three or more negative tests, two had recent HIV infection and four patients on antiretroviral therapy had undetectable plasma viral load. When patients positive in all the tests were compared with patients who had at least one negative test, only a plasma HIV RNA level <200 cp/ml was significantly associated with a false-negative result (p = 0.009). When the 33 rapid tests negative on FSB were repeated on serum, all but six (5 negative with OraQuick, 1 with INSTI) were positive. The sensitivity of OraQuick, Determine and Determine Ag/Ab Combo was significantly better on serum than on FSB (97.5%, p = 0.04; 100%, p = 0.004; and 100%, p = 0.02, respectively).

Conclusion

When evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum.     

Variation in Specificity of HIV Rapid Diagnostic Tests over Place and Time: An Analysis of Discordancy Data Using a Bayesian Approach

Background

Recent trends to earlier access to anti-retroviral treatment underline the importance of accurate HIV diagnosis. The WHO HIV testing strategy recommends the use of two or three rapid diagnostic tests (RDTs) combined in an algorithm and assume a population is serologically stable over time. Yet RDTs are prone to cross reactivity which can lead to false positive or discordant results. This paper uses discordancy data from Médecins Sans Frontières (MSF) programmes to test the hypothesis that the specificity of RDTs change over place and time.

Methods

Data was drawn from all MSF test centres in 2007-8 using a parallel testing algorithm. A Bayesian approach was used to derive estimates of disease prevalence, and of test sensitivity and specificity using the software WinBUGS. A comparison of models with different levels of complexity was performed to assess the evidence for changes in test characteristics by location and over time.

Results

106, 035 individuals were included from 51 centres in 10 countries using 7 different RDTs. Discordancy patterns were found to vary by location and time. Model fit statistics confirmed this, with improved fit to the data when test specificity and sensitivity were allowed to vary by centre and over time. Two examples show evidence of variation in specificity between different testing locations within a single country. Finally, within a single test centre, variation in specificity was seen over time with one test becoming more specific and the other less specific.

Conclusion

This analysis demonstrates the variable specificity of multiple HIV RDTs over geographic location and time. This variability suggests that cross reactivity is occurring and indicates a higher than previously appreciated risk of false positive HIV results using the current WHO testing guidelines. Given the significant consequences of false HIV diagnosis, we suggest that current testing and evaluation strategies be reviewed.     

A Human Immunodeficiency Virus Screening Algorithm to Address the High Rate of False-Positive Results in Pregnant Women in Japan

Background

Prenatal human immunodeficiency virus (HIV) testing is essential for the prevention of mother-to-child transmission. However, false-positive results of screening testing are a concern as they may cause unnecessary emotional stress to pregnant women waiting for confirmatory test results. In regions with an extremely low prevalence, the positive predictive values of screening are unacceptably low rate. Here, we propose a HIV screening algorithm consisting of serial two fourth-generation enzyme immunoassays to reduce the number of false-positive screening results.

Methodology/Principal Findings

When 6461 pregnant women presenting to two maternity hospitals located in the Tokyo metropolitan area of Japan from September, 2004 to January, 2006 were tested using Enzygnost HIV Integral as a first screening test, 27 showed positive reactions. When these positive reaction samples were tested using VIDAS HIV DUO Quick as a second screening test, only one of them had a positive reaction, and the remaining 26 were nonreactive. Confirmatory Western blots and nucleic acid amplification test also showed that one was positive and the remaining 26 were negative; the subject who was positive with the confirmatory tests was identical to the subject who was positive with the second screening test. Thus, by adding the second screening test, the false-positive rate was improved from 0.4% to 0%, and the positive predictive value from 3.7% to 100%, compared with the single screening test.

Conclusion

By applying our serial screening algorithm to HIV testing in maternity hospitals, many uninfected pregnant women would not need to receive confirmatory tests and be subjected to emotional turmoil while waiting for their confirmatory test results. This algorithm would be suitable for HIV testing of pregnant women living in low prevalence regions such as Japan.     

Provider-initiated HIV testing and counseling: increased uptake in two public community health centers in South Africa and implications for scale-up

Background

International guidance recommends the scale up of routinely recommended, offered, and delivered health care provider-initiated HIV testing and counseling (PITC) to increase the proportion of persons who know their HIV status. We compared HIV test uptake under PITC to provider-referral to voluntary counseling and testing (VCT referral) in two primary health centers in South Africa.

Methods

Prior to introducing PITC, clinical providers were instructed to refer systematically selected study participants to VCT. After PITC and HIV rapid test training, providers were asked to recommend, offer and provide HIV testing to study participants during the clinical consultation. Participants were interviewed before and after their consultation to assess their HIV testing experiences.

Results

HIV test uptake increased under PITC (OR 2.85, 95% CI 1.71, 4.76), and more patients felt providers answered their questions on HIV (104/141 [74%] versus 73/118 [62%] for VCT referral; p 0.04). After three months, only 4/106 (3.8%) HIV-positive patients had registered for onsite HIV treatment. Providers found PITC useful, but tested very few patients (range 0–15).

Conclusion

PITC increased the uptake of HIV testing compared with referral to onsite VCT, and patients reported a positive response to PITC. However, providing universal PITC will require strong leadership to train and motivate providers, and interventions to link HIV-positive persons to HIV treatment centers.     

Inaccurate Diagnosis of HIV-1 Group M and O Is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon

Background

Increased access to HIV testing is essential in working towards universal access to HIV prevention and treatment in resource-limited countries. We here evaluated currently used HIV diagnostic tests and algorithms in Cameroon for their ability to correctly identify HIV infections.

Methods

We estimated sensitivity, specificity, and positive and negative predictive values of 5 rapid/simple tests, of which 3 were used by the national program, and 2 fourth generation ELISAs. The reference panel included 500 locally collected samples; 187 HIV -1 M, 10 HIV-1 O, 259 HIV negative and 44 HIV indeterminate plasmas.

Results

None of the 5 rapid assays and only 1 ELISA reached the current WHO/UNAIDS recommendations on performance of HIV tests of at least 99% sensitivity and 98% specificity. Overall, sensitivities ranged between 94.1% and 100%, while specificities were 88.0% to 98.8%. The combination of all assays generated up to 9% of samples with indeterminate HIV status, because they reacted discordantly with at least one of the different tests. Including HIV indeterminate samples in test efficiency calculations significantly decreased specificities to a range from 77.9% to 98.0%. Finally, two rapid assays failed to detect all HIV-1 group O variants tested, with one rapid test detecting only 2 out of 10 group O specimens.

Conclusion

In the era of ART scaling-up in Africa, significant proportions of false positive but also false negative results are still observed with HIV screening tests commonly used in Africa, resulting in inadequate treatment and prevention strategies. Depending on tests or algorithms used, up to 6% of HIV-1 M and 80% of HIV-1 O infected patients in Cameroon do not receive ART and adequate counseling to prevent further transmission due to low sensitivities. Also, the use of tests with low specificities could imply inclusion of up to 12% HIV negative people in ART programs and increase budgets in addition to inconveniences caused to patients.     

Repeat confirmatory testing for persons with discordant whole blood and oral fluid rapid HIV test results: findings from post marketing surveillance

Background

Reactive oral fluid and whole blood rapid HIV tests must be followed with a confirmatory test (Western blot (WB), immunofluorescent assay (IFA) or approved nucleic acid amplification test (NAAT)). When the confirmatory result is negative or indeterminate (i.e. discordant with rapid result), repeat confirmatory testing should be conducted using a follow-up specimen. Previous reports have not described whether repeat testing adequately resolves the HIV-infection status of persons with discordant results.

Methodology

Post-marketing surveillance was conducted in 368 testing sites affiliated with 14 state and 2 city health departments from August 11, 2004 to June 30, 2005 and one health department through December 31, 2005. For persons with discordant results, data were collected on demographics, risk behaviors, HIV test results and specimen types. Persons with repeat confirmatory results were classified as HIV-infected or uninfected. Regression models were created to assess risk factors for not having repeat testing.

Principal Findings

Of 167,371 rapid tests conducted, 2589 (1.6%) were reactive: of these, 2417 (93%) had positive WB/IFA, 172 (7%) had negative or indeterminate WB/IFA. Of 89/172 (52%) persons with a repeat confirmatory test: 17 (19%) were HIV-infected, including 3 with indeterminate WB and positive NAAT; 72 (81%) were uninfected, including 12 with repeat indeterminate WB. Factors associated with HIV-infection included having an initial indeterminate WB/IFA (vs. negative) (p<0.001) and having an initial oral fluid WB (vs. serum) (p<0.001). Persons who had male-female sex (vs. male-male sex) were at increased risk for not having a repeat test [adjusted OR 2.6, 95% CI (1.3, 4.9)].

Conclusions

Though only half of persons with discordant results had repeat confirmatory testing, of those who did, nearly one in five were HIV-infected. These findings underscore the need for rapid HIV testing programs to increase repeat confirmatory testing for persons with discordant results. Because of the lower sensitivity of oral fluid WBs, confirmatory testing following a reactive rapid test should be conducted using serum or plasma, when possible.     

False Positive HIV Diagnoses in Resource Limited Settings: Operational Lessons Learned for HIV Programmes

Background

Access to HIV diagnosis is life-saving; however the use of rapid diagnostic tests in combination is vulnerable to wrongly diagnosing HIV infection when both screening tests give a false positive result. Misclassification of HIV patients can also occur due to poor quality control, administrative errors and lack of supervision and training of staff. Médecins Sans Frontières discovered in 2004 that HIV negative individuals were enrolled in some HIV programmes. This paper describes the result of an audit of three sites to review testing practices, implement improved testing algorithms and offer re-testing to clients enrolled in the HIV clinic.

Findings

In the Democratic Republic of Congo (DRC), Burundi and Ethiopia patients were identified for HIV retesting. In total, 44 false-positive patients were identified in HIV programmes in DRC, two in Burundi and seven in Ethiopia. Some of those identified had been abandoned by partners or started on anti-retroviral therapy or prophylaxis. Despite potential damage to programme reputations, no impact in terms of testing uptake occurred with mean monthly testing volumes stable after introduction of re-testing. In order to prevent the problem, training, supervision and quality control of testing procedures were strengthened. A simple and feasible confirmation test was added to the test algorithm. Prevalence of false positives after introducing the changes varied from zero percent (95% CI 0%–8.2%) to 10.3 percent (95% CI: 7.2%–14.1%) in Burundi and DRC respectively.

Conclusion

False HIV diagnoses were found in a variety of programme settings and had devastating individual consequences. We re-tested individuals in our programmes while instituting improved testing procedures without a negative impact on test uptake. Considering the importance of correct diagnosis to the individual, as well as the resources needed to care for someone with HIV, it is critical to ensure that all patients registered in HIV programmes are accurately diagnosed.     

Quality control and performance of HIV rapid tests in a microbicide clinical trial in rural KwaZulu-Natal

Background

Quality control (QC) and evaluation of HIV rapid test procedures are an important aspect of HIV prevention trials. We describe QC and performance of two rapid tests, Determine™ and Uni-Gold™ used in a microbicide clinical trial in rural KwaZulu-Natal, South Africa.

Methods/Results

Internal QC of both HIV rapid tests was conducted at the trial site using a Uni-Gold control kit (Uni-Gold™Recombigen® HIV). Both assays produced the expected results for a total of 4637 QC tests. Study participants were tested for HIV at screening and, if enrolled, at regular time points throughout the study. Positive or discordant results were confirmed by a double HIV immunoassay testing strategy at a local laboratory. Overall, 15292 HIV rapid test were performed. Sensitivity and specificity of Determine was 98.95% (95% CI: 97.72–99.61) and 99.83% (95% CI: 99.70–99.91) respectively [positive predictive value (PPV) 97.91% (95% CI: 96.38–98.92)], for Uni-Gold it was 99.30% (95% CI: 98.21–99.81) and 99.96% (95% CI: 99.88–99.99) respectively [PPV 99.47% (95% CI: 98.46–99.89)].

Conclusions

The results suggest that a Uni-Gold control kit can be used for internal QC of both Uni-Gold and the HIV-1 component of the Determine rapid tests. Both rapid tests performed proficiently in the trial population.     

Frequency of False Positive Rapid HIV Serologic Tests in African Men and Women Receiving PrEP for HIV Prevention: Implications for Programmatic Roll-Out of Biomedical Interventions

Background

Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.

Methods

We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests.

Results

A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits.

Conclusions

When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.     

Field Evaluation of Two Rapid Diagnostic Tests for Neisseria meningitidis Serogroup A during the 2006 Outbreak in Niger

The Pastorex^® (BioRad) rapid agglutination test is one of the main rapid diagnostic tests (RDTs) for meningococcal disease currently in use in the “meningitis belt”. Earlier evaluations, performed after heating and centrifugation of cerebrospinal fluid (CSF) samples, under good laboratory conditions, showed high sensitivity and specificity. However, during an epidemic, the test may be used without prior sample preparation. Recently a new, easy-to-use dipstick RDT for meningococcal disease detection on CSF was developed by the Centre de Recherche Médicale et Sanitaire in Niger and the Pasteur Institute in France. We estimate diagnostic accuracy in the field during the 2006 outbreak of Neisseria meningitidis serogroup A in Maradi, Niger, for the dipstick RDT and Pastorex^® on unprepared CSF, (a) by comparing each test''s sensitivity and specificity with previously reported values; and (b) by comparing results for each test on paired samples, using McNemar''s test. We also (c) estimate diagnostic accuracy of the dipstick RDT on diluted whole blood. We tested unprepared CSF and diluted whole blood from 126 patients with suspected meningococcal disease presenting at four health posts. (a) Pastorex^® sensitivity (69%; 95%CI 57–79) was significantly lower than found previously for prepared CSF samples [87% (81–91); or 88% (85–91)], as was specificity [81% (95%CI 68–91) vs 93% (90–95); or 93% (87–96)]. Sensitivity of the dipstick RDT [89% (95%CI 80–95)] was similar to previously reported values for ideal laboratory conditions [89% (84–93) and 94% (90–96)]. Specificity, at 62% (95%CI 48–75), was significantly lower than found previously [94% (92–96) and 97% (94–99)]. (b) McNemar''s test for the dipstick RDT vs Pastorex^® was statistically significant (p<0.001). (c) The dipstick RDT did not perform satisfactorily on diluted whole blood (sensitivity 73%; specificity 57%).Sensitivity and specificity of Pastorex^® without prior CSF preparation were poorer than previously reported results from prepared samples; therefore we caution against using this test during an epidemic if sample preparation is not possible. For the dipstick RDT, sensitivity was similar to, while specificity was not as high as previously reported during a more stable context. Further studies are needed to evaluate its field performance, especially for different populations and other serogroups.     

Role of Interferon Gamma Release Assay in Active TB Diagnosis among HIV Infected Individuals

Background

A rapid and specific test is urgently needed for tuberculosis (TB) diagnosis especially among human immunodeficiency virus (HIV) infected individuals. In this study, we assessed the sensitivity of Interferon gamma release assay (IGRA) in active tuberculosis patients who were positive for HIV infection and compared it with that of tuberculin skin test (TST).

Methodology/Principal Findings

A total of 105 HIV-TB patients who were naïve for anti tuberculosis and anti retroviral therapy were included for this study out of which 53 (50%) were culture positive. Of 105 tested, QuantiFERON-TB Gold in-tube (QFT-G) was positive in 65% (95% CI: 56% to 74%), negative in 18% (95% CI: 11% to 25%) and indeterminate in 17% (95% CI: 10% to 24%) of patients. The sensitivity of QFT-G remained similar in pulmonary TB and extra-pulmonary TB patients. The QFT-G positivity was not affected by low CD4 count, but it often gave indeterminate results especially in individuals with CD4 count <200 cells/µl. All of the QFT-G indeterminate patients whose sputum culture were positive, showed ≤0.25 IU/ml of IFN-γ response to phytohemagglutinin (PHA). TST was performed in all the 105 patients and yielded the sensitivity of 31% (95% CI: 40% to 22%). All the TST positives were QFT-G positives. The sensitivity of TST was decreased, when CD4 cell counts declined.

Conclusions/Significance

Our study shows neither QFT-G alone or in combination with TST can be used to exclude the suspicion of active TB disease. However, unlike TST, QFT-G yielded fewer false negative results even in individuals with low CD4 count. The low PHA cut-off point for indeterminate results suggested in this study (≤0.25 IU/ml) may improve the proportion of valid QFT-G results.     

False Positive Rate of Rapid Oral Fluid HIV Tests Increases as Kits Near Expiration Date

Background

Because a recent cluster of false positive results on the OraQuick ADVANCE® Rapid HIV-1/2 Antibody Test occurred in San Francisco on test kits close to their expiration date, we decided to assess the relationship between time to expiration and rate of false positive results from tests used with oral fluid.

Methodology/Principal Findings

We analyzed results of 20,904 tests with either an initial HIV-negative result (n = 20,828) or a preliminary positive result that was then negative on confirmatory tests (n = 76). We computed specificity for kits with time to expiration from ≤1 to ≥6 months, with exact binomial confidence intervals, then used logistic regression to estimate the independent association of time to expiration with false positive results, adjusting for site and technician effects. For 1,108 kits used in the last month before expiration, specificity was 98.83% (95% exact binomial confidence interval (CI) 98.00%–99.37%); the upper bound is below the claimed specificity of 99.60%. After adjustment using regression standardization for the effects of site, test lot, and technician factors, adjusted specificity in the last month before expiration was 99.18% (95% bootstrap confidence interval 98.60–99.57%).

Conclusions/Significance

We found that specificity of the OraQuick ADVANCE® with oral fluid declined significantly with ≤1 month remaining to expiration, leaving little margin for error from other sources.     

A Prospective Controlled Trial of Routine Opt-Out HIV Testing in a Men's Jail

Background

Approximately 10 million Americans enter jails annually. The Centers for Disease Control and Prevention now recommends routine opt-out HIV testing in these settings. The logistics for performing routine opt-out HIV testing within jails, however, remain controversial. The objective of this study was to evaluate the optimal time to routinely HIV test newly incarcerated jail detainees using an opt-out strategy.

Methods

This prospective, controlled trial of routine opt-out HIV testing was conducted among 298 newly incarcerated male inmates in an urban men''s jail in New Haven, Connecticut. 298 sequential entrants to the men''s jail over a three week period in March and April 2008 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 103), early (next day, n = 98), or delayed (7 days, n = 97). The primary outcome was the proportion of men in each group consenting to testing.

Results

Routine opt-out HIV testing was significantly higher for the early (53%: AOR = 2.6; 95% CI = 1.5 to 4.7) and immediate (45%: AOR = 2.3; 95% CI = 1.3 to 4.0) testing groups compared to the delayed (33%) testing group. The immediate and early testing groups, however, did not significantly differ (p = 0.67). In multivariate analyses, factors significantly associated with routine opt-out HIV testing were assignment to the ‘early’ testing group (p = 0.0003) and low (bond ≥$5,000, immigration or federal charges or pre-sentencing >30 days) likelihood of early release (p = 0.04). Two subjects received preliminary positive results and one of them was subsequently confirmed HIV seropositive.

Conclusions

In this men''s jail where attrition was high, routine opt-out HIV testing was not only feasible, but resulted in the highest rates of HIV testing when performed within 24 hours of incarceration.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00624247","term_id":"NCT00624247"}}NCT00624247     

Type-Specific Cervico-Vaginal Human Papillomavirus Infection Increases Risk of HIV Acquisition Independent of Other Sexually Transmitted Infections

Background

Sexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.

Methods and Findings

This prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18–49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09–4.15) or HPV 70 (aHR 2.68; 95% CI 1.08–6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02–2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16–3.30), HPV 31 (aHR 4.25; 95% CI 1.81–9.97) or HPV 70 (aHR 3.30; 95% CI 1.50–7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19–3.21) or excluded (aHR 1.96; 95% CI 1.02–2.85) from the analysis.

Conclusions/Significance

Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted.     

Cost effectiveness analysis of antenatal HIV screening in United Kingdom

ObjectiveTo assess the cost effectiveness of universal antenatal HIV screening compared with selective screening in the United Kingdom.DesignIncremental cost effectiveness analysis relating additional costs of screening to life years gained. Maternal and paediatric costs and life years were combined.SettingUnited Kingdom.ResultsOn base case assumptions, a new diagnosis of a pregnant woman with HIV results in a gain of 6.392 life years and additional expenditure of £14 833. If decision makers are prepared to pay up to £10 000 for an additional life year, this would imply a net benefit of £49 090 (range £12 300-£59 000), which would be available to detect each additional infected woman in an antenatal screening programme. In London, universal antenatal screening would be cost effective compared with a selective screening under any reasonable assumptions about screening costs. Outside London, universal screening with uptake above 90% would be cost effective with a £0.60 HIV antibody test cost and up to 3.5 minutes for pretest discussion. Cost effectiveness of universal testing is lower if selective testing can achieve high uptake among those at higher risk. A universal strategy with only 50% uptake may not be less cost effective in low prevalence districts and may cost more and be less effective than a well run selective strategy.ConclusionsUniversal screening with pretest discussion should be adopted throughout the United Kingdom as part of routine antenatal care as long as test costs can be kept low and uptake high.

Key messages

• In 1997 only 13% of undiagnosed HIV infection in pregnant women was picked up on antenatal testing, resulting in many preventable paediatric infections
• Assuming NHS willingness to pay £10 000 per life year gained, universal testing would be much more cost effective than selective testing throughout London on any reasonable assumptions on costs, prevalence, and uptake of testing
• Outside London, universal testing would also be cost effective, even allowing 2-4 minutes for pretest discussion, provided that test costs were no more than £0.60 and uptake exceeded 90%
• Low cost tests could be achieved by pooling antenatal sera or centralisation of testing
• Universal testing with uptake of 50% may be less cost effective than a well run selective programme

     

Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa

Background

Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART.

Methodology

Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis.

Findings

Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period.

Conclusion

Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.     

Male Perspectives on Incorporating Men into Antenatal HIV Counseling and Testing

Background

Male partner involvement in antenatal voluntary HIV counseling and testing (VCT) has been shown to increase uptake of interventions to reduce the risk of HIV transmission in resource-limited settings. We aimed to identify methods for increasing male involvement in antenatal VCT and determine male correlates of accepting couple counseling in these settings.

Methodology/Principal Findings

We invited women presenting to a Nairobi antenatal clinic to return with their male partners for individual or couples VCT. Male attitudes towards VCT and correlates of accompanying female partners to antenatal clinic and receiving couple counseling were determined. Of 1,993 women who invited their partner, 313 (16%) returned with their partners to ANC. Men attending antenatal clinic were married (>99%), employed (98%), and unlikely to report prior HIV testing (14%). Wanting an HIV test (87%) or health information (11%) were the most commonly cited reasons for attending. Most (95%) men who came to antenatal clinic accepted HIV testing and 39% elected to receive counseling as a couple. Men who received counseling with partners were younger, had fewer children, and were less knowledgeable about prevention of mother-to-child HIV transmission (PMTCT) than those who received counseling individually (p<0.05). Only 27% of men stated they would prefer HIV testing at a site other than the ANC. There was agreement between male and female reports for sociodemographic characteristics; however, men were more likely to report HIV preventive behaviors and health communication within the partnership than their partners (p<0.05).

Conclusions/Significance

Offering VCT services to men at antenatal clinic with options for couple and individual counseling is an important opportunity and acceptable strategy for increasing male involvement in PMTCT and promoting male HIV testing.     

Recent HIV-1 infection: identification of individuals with high viral load setpoint in a voluntary counselling and testing centre in rural Mozambique

Background

Identification of recent HIV-infections is important for describing the HIV epidemic and compiling HIV-RNA-setpoint data for future HIV intervention trials. We conducted a study to characterize recent infections, and HIV-RNA-setpoint within the adult population presenting at a voluntary counselling and testing centre (VCT) in southern Mozambique.

Methods

All adults attending the Manhiça District-Hospital VCT between April and October 2009 were recruited if they had at least one positive rapid HIV-serology test. Patients were screened for recent HIV-1 infection by BED-CEIA HIV-incidence test. Clinical examination, assessment of HIV-RNA and CD4 cell counts were performed at enrollment, 4 and 10 months.

Results

Of the 492 participants included in this study, the prevalence of recent infections as defined by BED-CEIA test, CD4 counts >200 cells/µl and HIV-RNA >400 copies/mL, was 11.58% (57/492; 95% CI 8.89–14.74). Due to heterogeneity in HIV-RNA levels in recently infected patients, individuals were categorized as having “high” HIV-RNA load if their HIV-RNA level was above the median (4.98 log₁₀ copies/mL) at diagnosis. The “high” HIV-RNA group sustained a significantly higher HIV-viral load at all visits with a median HIV-RNA setpoint of 5.22 log₁₀ copies/mL (IQR 5.18–5.47) as compared to the median of 4.15 log₁₀ copies/ml (IQR 3.37–4.43) for the other patients (p = 0.0001).

Conclusion

The low proportion of recent HIV-infections among HIV-seropositive VCT clients suggests that most of this population attends the VCT at later stages of HIV/AIDS. Characterization of HIV-RNA-setpoint may serve to identify recently infected individuals maintaining HIV viral load>5 log10 copies/mL as candidates for antiretroviral treatment as prevention interventions.     

Design,Development and Evaluation of rK28-Based Point-of-Care Tests for Improving Rapid Diagnosis of Visceral Leishmaniasis

Background

Visceral leishmaniasis (VL) is diagnosed by microscopic confirmation of the parasite in bone marrow, spleen or lymph node aspirates. These procedures are unsuitable for rapid diagnosis of VL in field settings. The development of rK39-based rapid diagnostic tests (RDT) revolutionized diagnosis of VL by offering high sensitivity and specificity in detecting disease in the Indian subcontinent; however, these tests have been less reliable in the African subcontinent (sensitivity range of 75–85%, specificity of 70–92%). We have addressed limitations of the rK39 with a new synthetic polyprotein, rK28, followed by development and evaluation of two new rK28-based RDT prototype platforms.

Methodology/Principal Findings

Evaluation of 62 VL-confirmed sera from Sudan provided sensitivities of 96.8% and 93.6% (95% CI = K28: 88.83–99.61%; K39: 84.30–98.21%) and specificities of 96.2% and 92.4% (95% CI = K28: 90.53–98.95%; K39: 85.54–96.65%) for rK28 and rK39, respectively. Of greater interest was the observation that individual VL sera with low rK39 reactivity often had much higher rK28 reactivity. This characteristic of the fusion protein was exploited in the development of rK28 rapid tests, which may prove to be crucial in detecting VL among patients with low rK39 antibody levels. Evaluation of two prototype lateral flow-based rK28 rapid tests on 53 VL patients in Sudan and 73 VL patients in Bangladesh provided promisingly high sensitivities (95.9% [95% CI = 88.46–99.1 in Sudan and 98.1% [95% CI = 89.93–99.95%] in Bangladesh) compared to the rK39 RDT (sensitivities of 86.3% [95% CI = 76.25–93.23%] in Sudan and 88.7% [95% CI = 76.97–95.73%] in Bangladesh).

Conclusions/Significance

Our study compares the diagnostic accuracy of rK39 and rK28 in detecting active VL cases and our findings indicate that rK28 polyprotein has great potential as a serodiagnostic tool. A new rK28-based RDT will prove to be a valuable asset in simplifying VL disease confirmation at the point-of-care.     

Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting

Background/Objective

The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF).

Methods

Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM.

Results

Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs. >200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98).

Conclusions

Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression.