Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial

Background Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. Methods and Findings Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. Conclusions In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation

HIV Surveillance in a Large, Community-Based Study: Results from the Pilot Study of Project Accept (HIV Prevention Trials Network 043)

<p>Abstract</p> <p>Background</p> <p>Project Accept is a community randomized, controlled trial to evaluate the efficacy of community mobilization, mobile testing, same-day results, and post-test support for the prevention of HIV infection in Thailand, Tanzania, Zimbabwe, and South Africa. We evaluated the accuracy of in-country HIV rapid testing and determined HIV prevalence in the Project Accept pilot study.</p> <p>Methods</p> <p>Two HIV rapid tests were performed in parallel in local laboratories. If the first two rapid tests were discordant (one reactive, one non-reactive), a third HIV rapid test or enzyme immunoassay was performed. Samples were designated HIV NEG if the first two tests were non-reactive, HIV DISC if the first two tests were discordant, and HIV POS if the first two tests were reactive. Samples were re-analyzed in the United States using a panel of laboratory tests.</p> <p>Results</p> <p>HIV infection status was correctly determined based on-in country testing for 2,236 (99.5%) of 2,247 participants [7 (0.37%) of 1,907 HIV NEG samples were HIV-positive; 2 (0.63%) of 317 HIV POS samples were HIV-negative; 2 (8.3%) of 24 HIV DISC samples were incorrectly identified as HIV-positive based on the in-country tie-breaker test]. HIV prevalence was: Thailand: 0.6%, Tanzania: 5.0%, Zimbabwe 14.7%, Soweto South Africa: 19.4%, Vulindlela, South Africa: 24.4%, (overall prevalence: 14.4%).</p> <p>Conclusions</p> <p>In-country testing based on two HIV rapid tests correctly identified the HIV infection status for 99.5% of study participants; most participants with discordant HIV rapid tests were not infected. HIV prevalence varied considerably across the study sites (range: 0.6% to 24.4%).</p> <p>Trial Registration</p> <p>ClinicalTrials.gov registry number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00203749">NCT00203749</a>.</p

Business’ role in exercising leadership, promoting equity, embracing accountability, and developing partnerships

The World Economic Forum, the Global Business Coalition on HIV/AIDS, and the South African Business Coalition on HIVand AIDS have placed the role of business in HIV/AIDS prevention and care high on their agendas. These groups have secured endorsement from leading companies for specific policies related to HIV/AIDS in the workplace. Business involvement in HIV/AIDS activities can occur at several levels. Industries and businesses can adopt policies and recommendations regarding HIV/AIDS in the workplace. They can spearhead treatment initiatives and routinely offer prevention and diagnostic services, such as voluntary counselling and testing, in the workplace and in communities. They can examine policy, economic, and structural barriers and facilitators to prevention and care, and engage in structural changes to produce better health outcomes. They can engage as leaders in advocating for similar businesses or their suppliers to adopt workplace policies and programmes. They can also engage in philanthropy that might stimulate and support government programmes, provide pilot grants to initiate programmes and research, build facilities and structures, or promote programmes that governments or other funders might avoid. In an effort to advance the discussion and implementation of business action on HIV/AIDS, the UCLA Program in Global Health at the David Geffen School of Medicine at the University of California, Los Angeles, USA, hosted a think tank in Durban, South Africa, from 21 to 23 June 2006. The meeting brought together businesses, civil society organizations and academic researchers from southern Africa, the United States, and Europe. Its goals were: To review and consider available evidence on the epidemiology and impact of HIV/AIDS in the workplace; To establish how businesses have responded to the HIV/AIDS epidemic, and document what is known about the efficacy of workplace prevention and care programmes; To assess the wider role of the private sector in advancing the key goals of accountability, equity and leadership in the fight against the virus; To determine future research needs and how those needs can be met; To make evidence-based programmatic and policy recommendations to maximize the contributions that the business sector can make towards HIV/AIDS prevention and care in South Africa

Quality assurance testing.

<p>Abbreviations: WB: Western blot; HIV Combo: ARCHITECT HIV Ag/Ab Combo assay.</p>a<p>The HIV status of study participants was initially characterized based on the results of the two HIV rapid tests performed in-country (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068349#s2" target="_blank">Methods</a>): HIV POS: two reactive HIV rapid tests. HIV DISC: one reactive and one non-reactive HIV rapid test. HIV NEG: two non-reactive HIV rapid tests. The testing algorithm used to confirm the HIV status of HIV NEG and HIV DISC samples (quality assurance testing) are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068349#pone-0068349-g001" target="_blank">Figure 1</a>. Quality assurance testing was only performed for HIV POS samples if results from the avidity assay suggested absent or extremely low levels of anti-HIV antibodies.</p>b<p>This indicates the number of samples that had reactive results using the HIV Combo assay (signal/cutoff >1). According to the package insert, specimens that are initially reactive with HIV Combo should be retested in duplicate and only repeatedly reactive specimens are considered reactive. In this study, samples were analyzed only once using the HIV Combo assay.</p>c<p>28 samples were excluded for reasons other than contamination, including: no CD4 cell count obtained (N = 5); insufficient quantity of plasma stored for testing (N = 2); failure of sample tracking (N = 17); protocol violation (N = 4).</p>d<p>These three samples were subsequently classified as MAA positive.</p>e<p>These three samples were subsequently classified as MAA negative.</p

Detection of antiretroviral drugs in study samples.

<p>Abbreviations: ARV: antiretroviral; MAA: multi-assay algorithm; N: number of samples/participants.</p

Algorithms used for quality assurance testing of study samples.

<p>The figure illustrates the testing algorithms that were used to determine and/or confirm the HIV status of study samples. This quality assurance testing was performed at the HPTN Network Laboratory (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068349#s2" target="_blank">Methods</a>). The algorithm used for quality assurance testing was determined by results obtained from HIV rapid testing performed at the study sites (for samples initially designated as HIV NEG, HIV DISC, and HIV POS, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068349#s2" target="_blank">Methods</a>). Quality assurance testing was performed for HIV POS samples if results from the avidity assay suggested absent or very low levels of anti-HIV antibodies (weird avidity). In this case, the HIV DISC algorithm was used to determine HIV status. Neg indicates that a negative or non-reactive test result was obtained. Pos indicates that a positive or reactive test result was obtained. Arrows (non-bolded) indicate the next step in sample testing. The following abbreviations were used to describe assays and tests used in the analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0068349#s2" target="_blank">Methods</a>): HIV Combo: ARCHITECT® HIV Ag/Ab Combo assay; EIA: Vitros EIA Human Immunodeficiency Virus Type 1 and/or 2 (HIV-1/2) Antibody Detection in Human Serum and Plasma; GA RNA: APTIMA® HIV-1 RNA Qualitative Assay; WB: Genetics System HIV-1 Western Blot.</p