"One teabag is better than four": Participants response to the discontinuation of 2% PRO2000/5 microbicide gel in KwaZulu-Natal, South Africa

Introduction

The Microbicides Development Programme evaluated the safety and effectiveness of 0.5% and 2% PRO2000/5 microbicide gels in reducing the risk of vaginally acquired HIV. In February 2008 the Independent Data Monitoring Committee recommended that evaluation of 2% PRO2000/5 gel be discontinued due to futility. The Africa Centre site systematically collected participant responses to this discontinuation.

Methods

Clinic and field staff completed field reports using ethnographic participant observation techniques. In-depth-interviews and focus group discussions were conducted with participants discontinued from 2% gel. A total of 72 field reports, 12 in-depth-interviews and 3 focus groups with 250 women were completed for this analysis. Retention of discontinued participants was also analysed. Qualitative data was analysed using NVivo 2 and quantitative data using STATA 10.0.

Results

Participants responded initially with fear that discontinuation was due to harm, followed by acceptance after effective messaging, and finally with disappointment. Participants reported that their initial fear was exacerbated by being contacted and advised to visit the clinic for information about the closure. Operational changes were subsequently made to the contact procedures. By incorporating feedback from participants, messages were continuously revised to ensure that information was comprehensible and misconceptions were addressed quickly thereby enabling participants to accept the discontinuation. Participants were disappointed that 2% PRO2000/5 was being excluded as a HIV prevention option, but also that they would no longer have access to gel that improved their sexual relationships with their partners and assisted condom negotiations. In total 238 women were discontinued from gel and 185 (78%) went on to complete their scheduled follow-up period.

Discussion

The use of qualitative social science techniques allowed the site team to amend operational procedures and messaging throughout the discontinuation period. This proved instrumental in ensuring that the discontinuation was successfully completed in a manner that was both understandable and acceptable to participants.

Trial registration

Current Controlled Trials. ISRCTN64716212.     

False-positive human immunodeficiency virus enzyme immunoassay results in pregnant women

Objective

Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others).

Design

To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008.

Methods

Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status.

Results

HIV prevalence was 0.06% among 921,438 pregnant women and 1.34% among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14% vs. 0.21%, odds ratio 0.65 [95% confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p<0.01) to have Western blot-negative (52.9% vs. 9.8%) and indeterminate results (17.0% vs. 3.7%) and lower PPV (30% vs. 87%). The p24 band was detected more often among pregnant women (p<0.01).

Conclusions

False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others. Pregnant women with reactive EIAs were more likely to have negative and indeterminate Western blot results due to lower HIV prevalence and higher p24 reactivity, respectively. Indeterminate results may complicate clinical management during pregnancy. Alternative methods are needed to rule out infection in persons with reactive EIAs from low prevalence populations.     

Detection of recent HIV-1 infection using a new limiting-antigen avidity assay: potential for HIV-1 incidence estimates and avidity maturation studies

Background

Accurate and reliable laboratory methods are needed for estimation of HIV-1 incidence to identify the high-risk populations and target and monitor prevention efforts. We previously described a single-well limiting-antigen avidity enzyme immunoassay (LAg-Avidity EIA) to detect recent HIV-1 infection.

Methods

We describe here further optimization and characterization of LAg-Avidity EIA, comparing it to the BED assay and a two-well avidity-index (AI) EIA. Specimen sets included longitudinal sera (n = 393), collected from 89 seroconverting individuals from 4 cohorts representing 4 HIV-1 subtypes, and sera from AIDS patients (n = 488) with or without TB co-infections from 3 different cohorts. Ninety seven HIV-1 positive specimens were purchased commercially. The BED assay, LAg-Avidity EIA, AI-EIA and HIV serology were performed, as needed.

Results

Monitoring quality control specimens indicated high reproducibility of the LAg-Avidity EIA with coefficient of variation of <10% in the dynamic range. The LAg-Avidity EIA has an overall mean duration of recency (ω) of 141 days (95% CI 119–160) at normalized optical density (ODn) cutoff of 1.0, with similar ω in different HIV-1 subtypes and populations (132 to 143 days). Antibody avidity kinetics were similar among individuals and subtypes by both the LAg-Avidity EIA and AI-EIA compared to the HIV-IgG levels measured by the BED assay. The false recent rate among individuals with AIDS was 0.2% with the LAg-Avidity EIA, compared to 2.9% with the BED assay. Western blot profiles of specimens with increasing avidity confirm accurate detection of recent HIV-1 infections.

Conclusions

These data demonstrate that the LAg-Avidity EIA is a promising assay with consistent ω in different populations and subtypes. The assay should be very useful for 1) estimating HIV-1 incidence in cross-sectional specimens as part of HIV surveillance, 2) identifying risk factors for recent infections, 3) measuring impact of prevention programs, and 4) studying avidity maturation during vaccine trials.     

Programmatic evaluation of a combined antigen and antibody test for rapid HIV diagnosis in a community and sexual health clinic screening programme

Background

A substantial proportion of HIV-infected individuals in the UK are unaware of their status and late presentations continue, especially in low prevalence areas. Fourth generation antigen/antibody rapid test kits could facilitate earlier diagnosis of HIV in non-clinical settings but lack data on performance under programmatic conditions.

Methods and Findings

We evaluated the performance of Determine HIV-1/2 Ag/Ab Combo Test (Determine Combo), a rapid test with indicators for both HIV antibodies and p24 antigen, in participants recruited from community outreach and hospital-based sexual health clinics. HIV infection was confirmed using laboratory enzyme-linked immunosorbent assay (EIA), Line Immuno Assay (LIA) and quantitative polymerase chain reaction (PCR). In total, 953 people underwent HIV testing. HIV antibody (Ab) prevalence was 1.8% (17/953). Four false positive rapid tests were identified: two antibody and two p24 antigen (Ag) reactions. Of participants diagnosed as HIV Ab positive, 2/17 (12%) were recent seroconverters based on clinical history and HIV antibody avidity test results. However, none of these were detected by the p24 antigen component of the rapid test kit. There were no other true positive p24 Ag tests.

Conclusion

These data lend support to an increasing body of evidence suggesting that 4th generation rapid HIV tests have little additional benefit over 3rd generation HIV kits for routine screening in low prevalence settings and have high rates of false positives. In order to optimally combine community-based case-finding among hard-to-reach groups with reliable and early diagnosis 3rd generation kits should be primarily used with laboratory testing of individuals thought to be at risk of acute HIV infection. A more reliable point of care diagnostic is required for the accurate detection of acute HIV infection under programmatic conditions.     

Estimation of HIV Incidence in a Large,Community-Based,Randomized Clinical Trial: NIMH Project Accept (HIV Prevention Trials Network 043)

Background

National Institute of Mental Health Project Accept (HIV Prevention Trials Network [HPTN] 043) is a large, Phase III, community-randomized, HIV prevention trial conducted in 48 matched communities in Africa and Thailand. The study intervention included enhanced community-based voluntary counseling and testing. The primary endpoint was HIV incidence, assessed in a single, cross-sectional, post-intervention survey of >50,000 participants.

Methods

HIV rapid tests were performed in-country. HIV status was confirmed at a central laboratory in the United States. HIV incidence was estimated using a multi-assay algorithm (MAA) that included the BED capture immunoassay, an avidity assay, CD4 cell count, and HIV viral load.

Results

Data from Thailand was not used in the endpoint analysis because HIV prevalence was low. Overall, 7,361 HIV infections were identified (4 acute, 3 early, and 7,354 established infections). Samples from established infections were analyzed using the MAA; 467 MAA positive samples were identified; 29 of those samples were excluded because they contained antiretroviral drugs. HIV prevalence was 16.5% (range at study sites: 5.93% to 30.8%). HIV incidence was 1.60% (range at study sites: 0.78% to 3.90%).

Conclusions

In this community-randomized trial, a MAA was used to estimate HIV incidence in a single, cross-sectional post-intervention survey. Results from this analysis were subsequently used to compare HIV incidence in the control and intervention communities.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00203749","term_id":"NCT00203749"}}NCT00203749     

Obtaining valid laboratory data in clinical trials conducted in resource diverse settings: lessons learned from a microbicide phase III clinical trial

Background

Over the last decade several phase III microbicides trials have been conducted in developing countries. However, laboratories in resource constrained settings do not always have the experience, infrastructure, and the capacity to deliver laboratory data meeting the high standards of clinical trials. This paper describes the design and outcomes of a laboratory quality assurance program which was implemented during a phase III clinical trial evaluating the efficacy of the candidate microbicide Cellulose Sulfate 6% (CS) [1].

Methodology

In order to assess the effectiveness of CS for HIV and STI prevention, a phase III clinical trial was conducted in 5 sites: 3 in Africa and 2 in India. The trial sponsor identified an International Central Reference Laboratory (ICRL), responsible for the design and management of a quality assurance program, which would guarantee the reliability of laboratory data. The ICRL provided advice on the tests, assessed local laboratories, organized trainings, conducted supervision visits, performed re-tests, and prepared control panels. Local laboratories were provided with control panels for HIV rapid tests and Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG) amplification technique. Aliquots from respective control panels were tested by local laboratories and were compared with results obtained at the ICRL.

Results

Overall, good results were observed. However, discordances between the ICRL and site laboratories were identified for HIV and CT/NG results. One particular site experienced difficulties with HIV rapid testing shortly after study initiation. At all sites, DNA contamination was identified as a cause of invalid CT/NG results. Both problems were timely detected and solved. Through immediate feedback, guidance and repeated training of laboratory staff, additional inaccuracies were prevented.

Conclusions

Quality control guidelines when applied in field laboratories ensured the reliability and validity of final study data. It is essential that sponsors provide adequate resources for implementation of such comprehensive technical assessment and monitoring systems.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00153777","term_id":"NCT00153777"}}NCT00153777 and Current Controlled Trials ISRCTN95638385     

Comparative Performance of Electrochemiluminescence Immunoassay and EIA for HIV Screening in a Multiethnic Region of China

Background

The recent approval of 4th generation HIV tests has forced many laboratories to decide whether to shift from 3rd to these tests. There are limited published studies on the comparative evaluation of these two different assays. We compare the performance of fourth-generation electrochemiluminescence immunoassay (ChIA) and third-generation enzyme linked immunosorbent assay (EIA) for human immunodeficiency virus (HIV) screening and gauge whether the shift from EIA to ChIA could be better in a multiethnic region of China.

Methodology/Principal Findings

We identified a large number of routine specimens (345,492) using two different assays from Jan 2008 to Aug 2011 in a teaching hospital with high sample throughput. Of the 344,596 specimens with interpretable HIV test results, 526(0.23%) of 228,761 using EIA and 303(0.26%) of 115,835 using ChIA were HIV-1 positive. The false-positive rate of EIA was lower than that of ChIA [0.03% vs. 0.08%, odds ratio 0.33 (95% confidence interval 0.24, 0.45)]. The positive predictive value (PPV) of EIA (89.6%) was significantly higher than that of ChIA (76.1%) (<0.001), reflecting the difference between the two assays. The clinical sensitivities of two assays in this study were 99.64% for EIA and 99.88% for ChIA.

Conclusion

Caution is needed before shifting from 3rd to 4th generation HIV tests. Since none of these tests are perfect, different geographic and ethnic area probably require different considerations with regard to HIV testing methods, taking into account the local conditions.     

Similar Evolution of Cellular HIV-1 DNA Level in Darunavir/Ritonavir Monotherapy versus Triple Therapy in MONOI -ANRS136 Trial over 96 Weeks

Background

A higher proportion of intermittent viremia (to have a HIV-1 RNA viral load>50 copies/mL not confirmed) was reported in the boosted protease inhibitor monotherapy arm in some studies including MONOI trial, and that could have an impact on the replenishment of the HIV-1 DNA reservoirs. The HIV-1 DNA level is an interesting marker which reflects the size of cellular HIV reservoir. Our objectives were to study the impact of 96 weeks of Darunavir/ritonavir monotherapy versus a triple standard combination on the HIV-1 blood reservoir and factors associated with HIV-1 plasma DNA at baseline in MONOI trial sub-study.

Methodology/Principal Findings

This sub-study is focused on 160 patients (79 patients in monotherapy arm and 81 in tritherapy arm) for whom blood cells were available both at baseline and at week 96 (W96). Baseline HIV-1 plasma DNA was associated with CD4 nadir, pre therapeutic HIV-1 RNA viral load and baseline HIV-1 RNA measured by ultrasensitive assay. A similar median delta HIV-DNA was observed between D0 and W96 in both arms; 0.35 log copies/10⁶ leucocytes in monotherapy arm versus 0.51 log copies/10⁶ leucocytes in tritherapy arm.

Conclusion/Significance

Despite a higher proportion of intermittent viremia in monotherapy arm, a similar evolution of cellular HIV-1 DNA level was observed between mono and triple therapy arm.

Trial Registration

ClinicalTrials. gov {"type":"clinical-trial","attrs":{"text":"NCT00421551","term_id":"NCT00421551"}}NCT00421551 <{"type":"clinical-trial","attrs":{"text":"NCT00421551","term_id":"NCT00421551"}}NCT00421551>     

SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria

Background

The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.

Methodology/Principal Findings

This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1∶1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use.

Conclusions/Significance

SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00130078","term_id":"NCT00130078"}}NCT00130078     

Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054)

Background

Individuals without prior immunity to a vaccine vector may be more sensitive to reactions following injection, but may also show optimal immune responses to vaccine antigens. To assess safety and maximal tolerated dose of an adenoviral vaccine vector in volunteers without prior immunity, we evaluated a recombinant replication-defective adenovirus type 5 (rAd5) vaccine expressing HIV-1 Gag, Pol, and multiclade Env proteins, VRC-HIVADV014-00-VP, in a randomized, double-blind, dose-escalation, multicenter trial (HVTN study 054) in HIV-1-seronegative participants without detectable neutralizing antibodies (nAb) to the vector. As secondary outcomes, we also assessed T-cell and antibody responses.

Methodology/Principal Findings

Volunteers received one dose of vaccine at either 10¹⁰ or 10¹¹ adenovector particle units, or placebo. T-cell responses were measured against pools of global potential T-cell epitope peptides. HIV-1 binding and neutralizing antibodies were assessed. Systemic reactogenicity was greater at the higher dose, but the vaccine was well tolerated at both doses. Although no HIV infections occurred, commercial diagnostic assays were positive in 87% of vaccinees one year after vaccination. More than 85% of vaccinees developed HIV-1-specific T-cell responses detected by IFN-γ ELISpot and ICS assays at day 28. T-cell responses were: CD8-biased; evenly distributed across the three HIV-1 antigens; not substantially increased at the higher dose; and detected at similar frequencies one year following injection. The vaccine induced binding antibodies against at least one HIV-1 Env antigen in all recipients.

Conclusions/Significance

This vaccine appeared safe and was highly immunogenic following a single dose in human volunteers without prior nAb against the vector.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00119873","term_id":"NCT00119873"}}NCT00119873     

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.     

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania

Background

Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania.

Methods

Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA.

Results

Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32–47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97–439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2–13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8–99.6%) and specificity at 100% (95% CI, 98.9–100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0–6.4%) of patients.

Conclusion

This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.     

Safety and efficacy of the 10-day melarsoprol schedule for the treatment of second stage rhodesiense sleeping sickness

Objective

Assessment of the safety and efficacy of a 10-day melarsoprol schedule in second stage T.b. rhodesiense patients and the effect of suramin-pretreatment on the incidence of encephalopathic syndrome (ES) during melarsoprol therapy.

Design

Sequential conduct of a proof-of-concept trial (n = 60) and a utilization study (n = 78) using historic controls as comparator.

Setting

Two trial centres in the T.b. rhodesiense endemic regions of Tanzania and Uganda. Participants: Consenting patients with confirmed second stage disease and a minimum age of 6 years were eligible for participation. Unconscious and pregnant patients were excluded.

Main Outcome Measures

The primary outcome measures were safety and efficacy at end of treatment. The secondary outcome measure was efficacy during follow-up after 3, 6 and 12 months.

Results

The incidence of ES in the trial population was 11.2% (CI 5–17%) and 13% (CI 9–17%) in the historic data. The respective case fatality rates were 8.4% (CI 3–13.8%) and 9.3% (CI 6–12.6%). All patients discharged alive were free of parasites at end of treatment. Twelve months after discharge, 96% of patients were clinically cured. The mean hospitalization time was reduced from 29 to 13 days (p<0.0001) per patient.

Conclusions

The 10-day melarsoprol schedule does not expose patients to a higher risk of ES or death than does treatment according to national schedules in current use. The efficacy of the 10-day melarsoprol schedule was highly satisfactory. No benefit could be attributed to the suramin pre-treatment.

Trial Registration

Current Controlled Trials ISRCTN40537886     

Effectiveness of family meetings for family caregivers on delaying time to nursing home placement of dementia patients: a randomized trial

Background

Interventions relieving the burden of caregiving may postpone or prevent patient institutionalization. The objective of this study was to determine whether a family meetings intervention was superior to usual care in postponing nursing home placement of patients with dementia.

Methods

A randomized multicenter trial was conducted among 192 patients with a clinical diagnosis of dementia living at home at enrolment and their primary family caregiver. Dyads of caregivers and patients were randomized to the family meetings intervention (n = 96) or usual care (n = 96) condition. The intervention consisted of two individual sessions with the primary caregiver and four family counseling sessions that included family members and friends. The primary outcome measure was the time until institutionalization of the patient. Intention-to-treat as well as per protocol analyses were performed. Survival analyses were carried out to evaluate the effectiveness of the intervention.

Results

During 18 months follow-up 23 of 96 relatives with dementia of caregivers in the intervention group and 18 of 96 relatives with dementia of caregivers in the usual care group were institutionalized. No significant difference between the intervention and the usual care group was found in time until institutionalization (adjusted hazard ratio (HR) 1.46, 95% confidence interval (CI) 0.78 to 2.74). The per-protocol analysis revealed no significant effect either (adjusted HR 0.57, 95% CI 0.21 to 1.57), although the number of placements among the adherers was relatively low (9.4%). A subgroup effect was found for patients’ age, with a significantly higher risk of institutionalization for ‘younger’ patients in the intervention group compared with the usual care group (adjusted HR = 4.94, 95% CI 1.10 to 22.13).

Conclusion

This family meetings intervention for primary caregivers of patients with dementia did not postpone patient institutionalization more than usual care.

Trial Registration: Controlled-Trials.com ISRCTN90163486

     

Detection of antibodies to HIV in homologous sets of plasma, urine and oral mucosal transudate samples using rapid assays in Tanzania

The aim of this study was to evaluate the performance of commercially available anti-HIV assays when testing plasma, urine and oral mucosal transudate (OMT) samples for the presence of antibodies to HIV. Homologous sets of plasma, urine and oral mucosal transudate specimens were collected from 288 hospitalized patients in northern Tanzania and tested for antibodies to HIV using a routine enzyme immunoassay (Recombinant 3rd Generation EIA, Abbott) and two rapid assays (Testpack HIV-1/HIV-2; Abbott and SUDS HIV-1, Murex). Incubation times and/or sample volumes when testing OMT or urine were increased as compared to those recommended for plasma. The corresponding plasma specimens from all repeatedly reactive samples and samples presenting discordant results were subjected to confirmational testing by an HIV-1/2 Western blot. A total of 15.3% (44/288) of the plasma samples were anti-HIV-1 positive by Western blot. The sensitivity using plasma was 100% by all assays, 69.7-97.7% using urine, and 92.7-100% using oral transudate specimens. The sensitivity of both rapid assays was excellent and higher than the EIA when testing OMT. Specificities ranged from 98.8-100% for plasma, 99-100% for urine and were 100% by all assays using oral samples. The results obtained using oral mucosal transudate specimens and rapid assays were at least comparable to those obtained with plasma, while the use of urine specimens produced suboptimal sensitivities with two of the three assays. The testing of alternative body fluids for antibodies to HIV is yet another strategy that may be applicable, particularly in developing countries.     

Multi-Centre Evaluation of the Determine HIV Combo Assay when Used for Point of Care Testing in a High Risk Clinic-Based Population

Background

Determine HIV Combo (DHC) is the first point of care assay designed to increase sensitivity in early infection by detecting both HIV antibody and antigen. We conducted a large multi-centre evaluation of DHC performance in Sydney sexual health clinics.

Methods

We compared DHC performance (overall, by test component and in early infection) with conventional laboratory HIV serology (fourth generation screening immunoassay, supplementary HIV antibody, p24 antigen and Western blot tests) when testing gay and bisexual men attending four clinic sites. Early infection was defined as either acute or recent HIV infection acquired within the last six months.

Results

Of 3,190 evaluation specimens, 39 were confirmed as HIV-positive (12 with early infection) and 3,133 were HIV-negative by reference testing. DHC sensitivity was 87.2% overall and 94.4% and 0% for the antibody and antigen components, respectively. Sensitivity in early infection was 66.7% (all DHC antibody reactive) and the DHC antigen component detected none of nine HIV p24 antigen positive specimens. Median HIV RNA was higher in false negative than true positive cases (238,025 vs. 37,591 copies/ml; p = 0.022). Specificity overall was 99.4% with the antigen component contributing to 33% of false positives.

Conclusions

The DHC antibody component detected two thirds of those with early infection, while the DHC antigen component did not enhance performance during point of care HIV testing in a high risk clinic-based population.     

Nurse-Led,Telephone-Based,Secondary Preventive Follow-Up after Stroke or Transient Ischemic Attack Improves Blood Pressure and LDL Cholesterol: Results from the First 12 Months of the Randomized,Controlled NAILED Stroke Risk Factor Trial

Background

Enhanced secondary preventive follow-up after stroke or transient ischemic attack (TIA) is necessary for improved adherence to recommendations regarding blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels. We investigated whether nurse-led, telephone-based follow-up was more efficient than usual care at improving BP and LDL-C levels at 12 months after hospital discharge.

Methods

We randomized 537 patients to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C measurements were performed at 1 month (baseline) and 12 months post-discharge. Intervention group patients who did not meet target values at baseline received additional follow-up, including titration of medication and lifestyle counselling, to reach treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L).

Results

At 12 months, mean systolic BP, diastolic BP and LDL-C was 3.3 (95% CI 0.3 to 6.3) mmHg, 2.3 mmHg (95% CI 0.5 to 4.2) and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group compared to controls. Among participants with values above the treatment goal at baseline, the difference in systolic BP and LDL-C was more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1, and 0.6 mmol/L, 95% CI 0.4 to 0.9). A larger proportion of the intervention group reached the treatment goal for systolic BP (68.5 vs. 56.8%, p = 0.008) and LDL-C (69.7% vs. 50.4%, p < 0.001).

Conclusions

Nurse-led, telephone-based secondary preventive follow-up, including medication adjustment, was significantly more efficient than usual care at improving BP and LDL-C levels by 12 months post-discharge.

Trial Registration

ISRCTN Registry ISRCTN23868518     

Subtype Classification of Iranian HIV-1 Sequences Registered in the HIV Databases, 2006-2013

Background

The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory.

Methods

All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods.

Results

A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported.

Conclusions

Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.     

Personalised Normative Feedback for Preventing Alcohol Misuse in University Students: Solomon Three-Group Randomised Controlled Trial

Background

Young people tend to over-estimate peer group drinking levels. Personalised normative feedback (PNF) aims to correct this misperception by providing information about personal drinking levels and patterns compared with norms in similar aged peer groups. PNF is intended to raise motivation for behaviour change and has been highlighted for alcohol misuse prevention by the British Government Behavioural Insight Team. The objective of the trial was to assess the effectiveness of PNF with college students for the prevention of alcohol misuse.

Methodology

Solomon three-group randomised controlled trial. 1751 students, from 22 British Universities, allocated to a PNF group, a normal control group, or a delayed measurement control group to allow assessment of any measurement effects. PNF was provided by email. Participants completed online questionnaires at baseline, 6- and 12-months (only 12-months for the delayed measurement controls). Drinking behaviour measures were (i) alcohol disorders; (ii) frequency; (iii) typical quantity, (iv) weekly consumption; (v) alcohol-related problems; (vi) perceived drinking norms; and (vii) positive alcohol expectancies. Analyses focused on high-risk drinkers, as well as all students, because of research evidence for the prevention paradox in student drinkers.

Principal Findings

Follow-up rates were low, with only 50% and 40% responding at 6- and 12-months, respectively, though comparable to similar European studies. We found no evidence for any systematic attrition bias. Overall, statistical analyses with the high risk sub-sample, and for all students, showed no significant effects of the intervention, at either time-point, in a completed case analysis and a multiple imputation analysis.

Conclusions

We found no evidence for the effectiveness of PNF for the prevention of alcohol misuse and alcohol-related problems in a UK student population.

Registration

Controlled-Trials.com ISRCTN30784467