Electronic Partner Notification for Sexually Transmitted Infections: A Qualitative Assessment of Patient, Clinical Staff, and State Field Epidemiologist Perspectives.

In Massachusetts (MA), partner notification is routinely offered for new HIV and infectious syphilis cases, but there are no formal partner notification services for gonorrhea and chlamydia. Electronic partner notification (ePN), which allows patients to anonymously notify their partners of sexually transmitted infection exposure, could fill this gap. We evaluated the acceptability of and ideal characteristics for a statewide ePN service in MA. We performed semistructured interviews with patients at a Boston area sexual health clinic and conducted focus groups with clinicians and Massachusetts Department of Public Health Field Epidemiologists (FEs). We developed a codebook and thematically analyzed interview and focus group data; 25% of interviews were double coded. We identified six main themes from our data: (1) partner notification is a relational process and (2) partner notification is situation dependent. There are three pairs of challenges and core values for an effective ePN system: (3) stigmatization versus inclusivity, (4) trust versus mistrust, and (5) privacy versus helpful information sharing. Therefore, (6) a statewide ePN platform must be customizable at each possible step. Although ePN was acceptable across all three groups, the likelihood of individual use was grounded in a patient's sociocultural context, interpersonal relationships, trust in the platform and health authorities, desire to avoid stigmatization, and privacy needs. These factors are best accommodated by a platform that adapts to users' preferences and needs. ePN presents an opportunity to link partners at risk for gonorrhea or chlamydia to clinical care that is complementary to the more labor-intensive FE role.

Evaluation of four chemotherapy regimens for treatment of advanced AIDS-associated Kaposi sarcoma in Kenya: a cost-effectiveness analysis.

BACKGROUND: The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan Africa due to limited availability and high cost. We examined the clinical impact, costs, and cost-effectiveness of paclitaxel or PLD in Kenya, compared with etoposide or bleomycin-vincristine. METHODS: In this study, we use the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International Model to project clinical outcomes and costs among people living with HIV and advanced Kaposi sarcoma on antiretroviral therapy. We compared four different treatment strategies: etoposide, bleomycin-vincristine, paclitaxel, or PLD. We derived cohort characteristics and costs from the Kenyan Academic Model for Providing Access to Healthcare network, and adverse events, efficacy, and mortality from clinical trials. We projected model outcomes over a lifetime and included life expectancy, per-person lifetime costs, and incremental cost-effectiveness ratios (ICERs). We conducted budget impact analysis for 5-year total costs and did deterministic and probabilistic sensitivity analyses to evaluate the effect of uncertainty in input parameters. FINDINGS: We found that paclitaxel would be more effective than bleomycin-vincristine and would increase life expectancy by 4·2 years per person. PLD would further increase life expectancy by 0·6 years per person. Paclitaxel would be the most cost-effective strategy (ICER US$380 per year-of-life-saved compared with bleomycin-vincristine) and would remain cost-effective across a range of scenarios. PLD would be cost-effective compared with paclitaxel if its price were reduced to $100 per cycle (base case $180 per cycle). Implementing paclitaxel instead of bleomycin-vincristine would save approximately 6400 life-years and would increase the overall 5-year Kenyan health-care costs by $3·7 million; increased costs would be primarily related to ongoing HIV care given improved survival. INTERPRETATION: Paclitaxel would substantially increase life expectancy and be cost-effective compared with bleomycin-vincristine for advanced AIDS-associated Kaposi sarcoma in Kenya and should be the standard of care. PLD would further improve survival and be cost-effective with a 44% price reduction. FUNDING: US National Institutes of Health and Massachusetts General Hospital. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.

Modeling Adherence Interventions Among Youth with HIV in the United States: Clinical and Economic Projections.

The Adolescent Medicine Trials Network for HIV/AIDS Interventions is evaluating treatment adherence interventions (AI) to improve virologic suppression (VS) among youth with HIV (YWH). Using a microsimulation model, we compared two strategies: standard-of-care (SOC) and a hypothetical 12-month AI that increased cohort-level VS in YWH in care by an absolute ten percentage points and cost $100/month/person. Projected outcomes included primary HIV transmissions, deaths and life-expectancy, lifetime HIV-related costs, and incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). Compared to SOC, AI would reduce HIV transmissions by 15% and deaths by 12% at 12 months. AI would improve discounted life expectancy/person by 8 months at an added lifetime cost/person of $5,300, resulting in an ICER of $7,900/QALY. AI would be cost-effective at $2,000/month/person or with efficacies as low as a 1 percentage point increase in VS. YWH-targeted adherence interventions with even modest efficacy could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.

RESUMEN: La Red de Ensayos Médicos sobre Adolescentes para Realizar Intervenciones sobre el VIH/SIDA está evaluando intervenciones de adherencia (IAs) al tratamiento para mejorar la supresión virológica (SV) entre los jóvenes con VIH (JCV). Usando un modelo de microsimulación, comparamos dos estrategias: cuidado convencional (CC) y una intervención de adherencia hipotética durando 12 meses que aumentaría la SV a nivel de cohorte entre JCV en tratamiento por 10 puntos de porcentuales y que costaría US$ 100/mes/persona. Resultados proyectados incluyeron transmisiones de VIH primarias, muertes y esperanza de vida, costos de por vida asociados con el VIH, y razones incrementales de costo-efectividad (RICEs, $/año de vida ajustado por la calidad [AVAC]). Comparado al CC, la IA reduciría transmisiones de VIH por 15% y muertes por 12% a los 12 meses. La IA mejoraría esperanza de vida descontada/persona por 8 meses a un costo de por vida adicional/persona de US$ 5.300, resultando en una RICE de US$ 7.900/AVAC. La IA sería costo-efectiva a un costo de US$ 2.000/mes/persona o si mejorara SV por al menos un punto porcentual. Intervenciones de adherencia dirigidas a jóvenes con una eficacia incluso modesta podrían mejorar esperanza de vida, prevenir transmisiones de VIH, y ser costo-efectivas.

Global migration of clinical research during the era of trial registration.

BACKGROUND: Since the site of human subjects research has public health, regulatory, ethical, economic, and social implications, we sought to determine the global distribution and migration of clinical research using an open-access trial registry. METHODS: We obtained individual clinical trial data including location of trial sites, dates of operation, funding source (United States government, pharmaceutical industry, or organization), and clinical study phase (1, 1/2, 2, 2/3, or 3) from ClinicalTrials.gov. We used the World Bank's classification of each country's economic development status ["High Income and a Member of the Organization for Economic Co-operation and Development (OECD)", "High Income and Non-Member of the OECD", "Upper-Middle Income", "Lower-Middle Income", or "Low Income"] and United Nations Populations Division data for country-specific population estimates. We analyzed data from calendar year 2006 through 2012 by number of clinical trial sites, cumulative trial site-years, trial density (trial site-years/106 population), and annual growth rate (%) for each country, and by development category, funding source, and clinical study phase. RESULTS: Over a 7-year period, 89,647 clinical trials operated 784,585 trial sites in 175 countries, contributing 2,443,850 trial site-years. Among those, 652,200 trial sites (83%) were in 25 high-income OECD countries, while 37,195 sites (5%) were in 91 lower-middle or low-income countries. Trial density (trial site-years/106 population) was 540 in the United States, 202 among other high-income OECD countries (excluding the United States), 81 among high-income non-OECD countries, 41 among upper-middle income countries, 5 among lower-middle income countries, and 2 among low-income countries. Annual compound growth rate was positive (ranging from 0.8% among low-income countries to 14.7% among lower-middle income countries) among all economic groups, except the United States (-0.5%). Overall, 29,191 trials (33%) were funded by industry, 4,059 (5%) were funded by the United States government, and 56,397 (63%) were funded by organizations. Countries with emerging economies (low- and middle-income) operated 19% of phase 3 trial sites, as compared to only 6% of phase 1 trial sites. CONCLUSION: Human clinical research remains concentrated in high-income countries, but operational clinical trial sites, particularly for phase 3 trials, may be migrating to low- and middle-income countries with emerging economies.

A Comparison of Home-Based Versus Outreach Event-Based Community HIV Testing in Ugandan Fisherfolk Communities.

We compared two community-based HIV testing models among fisherfolk in Lake Victoria, Uganda. From May to July 2015, 1364 fisherfolk residents of one island were offered (and 822 received) home-based testing, and 344 fisherfolk on another island were offered testing during eight community mobilization events (outreach event-based testing). Of 207 home-based testing clients identified as HIV-positive (15% of residents), 82 were newly diagnosed, of whom 31 (38%) linked to care within 3 months. Of 41 who screened positive during event-based testing (12% of those tested), 33 were newly diagnosed, of whom 24 (75%) linked to care within 3 months. Testing costs per capita were similar for home-based ($45.09) and event-based testing ($46.99). Compared to event-based testing, home-based testing uncovered a higher number of new HIV cases but was associated with lower linkage to care. Novel community-based test-and-treat programs are needed to ensure timely linkage to care for newly diagnosed fisherfolk.

Financial incentives to improve progression through the HIV treatment cascade.

PURPOSE OF REVIEW: We reviewed recent literature on conditional and unconditional financial incentives for their impact on improving movement through the HIV care cascade and HIV prevention. RECENT FINDINGS: Concepts from behavioral economics may help improve engagement in HIV care by addressing upstream structural risk factors for HIV, such as poverty, or providing conditional rewards for immediate, measurable outcomes related to HIV care. Incentives have been shown to increase uptake of HIV testing. Yet, few studies to date focus on linkage to care: one large USA-based randomized trial failed to show an effect of incentives; and a smaller trial showed improved linkage to care among drug users, but no difference in virologic suppression. Several small USA-based studies have shown an impact of financial incentives on antiretroviral therapy adherence, but without durability beyond the incentive period. HIV prevention has the most robust evidence for decreasing HIV risk-taking behavior among adolescents and may serve as a model for research on the care cascade. SUMMARY: Financial incentives show promise for improving engagement in HIV testing, care, and prevention. Understanding the durability, scalability, ease of implementation, and cost-effectiveness of these different approaches will be critical for maximizing the impact of incentives in curtailing the HIV epidemic.

The clinical and economic impact of point-of-care CD4 testing in mozambique and other resource-limited settings: a cost-effectiveness analysis.

BACKGROUND: Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. METHODS AND FINDINGS: We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%-61.0%), increasing to 65.0% (95% CI, 64.9%-65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6-9.6 y) and US$2,440 (95% CI, US$2,440-US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3-10.3 y) and US$2,800 (95% CI, US$2,790-US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480-US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. CONCLUSIONS: POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summary.

Mobile HIV screening in Cape Town, South Africa: clinical impact, cost and cost-effectiveness.

BACKGROUND: Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. METHODS AND FINDINGS: We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%-58%, females 49%-58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, $29.30 per negative result and $31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be "very cost-effective" when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) ($8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was $2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. CONCLUSION: The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority.

Diagnostic point-of-care tests in resource-limited settings.

The aim of diagnostic point-of-care testing is to minimise the time to obtain a test result, thereby allowing clinicians and patients to make a quick clinical decision. Because point-of-care tests are used in resource-limited settings, the benefits need to outweigh the costs. To optimise point-of-care testing in resource-limited settings, diagnostic tests need rigorous assessments focused on relevant clinical outcomes and operational costs, which differ from assessments of conventional diagnostic tests. We reviewed published studies on point-of-care testing in resource-limited settings, and found no clearly defined metric for the clinical usefulness of point-of-care testing. Therefore, we propose a framework for the assessment of point-of-care tests, and suggest and define the term test efficacy to describe the ability of a diagnostic test to support a clinical decision within its operational context. We also propose revised criteria for an ideal diagnostic point-of-care test in resource-limited settings. Through systematic assessments, comparisons between centralised testing and novel point-of-care technologies can be more formalised, and health officials can better establish which point-of-care technologies represent valuable additions to their clinical programmes.

Linkage to HIV, TB and non-communicable disease care from a mobile testing unit in Cape Town, South Africa.

BACKGROUND: HIV counseling and testing may serve as an entry point for non-communicable disease screening. OBJECTIVES: To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. METHODS: A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. RESULTS: Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. CONCLUSION: Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care.

The clinical impact and cost-effectiveness of routine, voluntary HIV screening in South Africa.

BACKGROUND: Although 900,000 HIV-infected South Africans receive antiretroviral therapy, the majority of South Africans with HIV remain undiagnosed. METHODS: We use a published simulation model of HIV case detection and treatment to examine 3 HIV screening scenarios, in addition to current practice as follows: (1) one-time; (2) every 5 years; and (3) annually. South African model input data include the following: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including 2 sequential antiretroviral therapy regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness. RESULTS: HIV screening one-time, every 5 years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6, and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every 5 years. Screening every 5 years and annually each have incremental cost-effectiveness ratios of $1570/quality-adjusted life year and $1720/quality-adjusted life year. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case. CONCLUSIONS: In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment.

Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa.

BACKGROUND: The World Health Organization (WHO) recommends cough as the trigger for tuberculosis screening in human immunodeficiency virus (HIV)-infected patients, with acid-fast bacillus (AFB) smear as the initial diagnostic test. Our objective was to assess the yield and cost of a more intensive tuberculosis screening in HIV-infected patients starting antiretroviral therapy (ART) in Durban, South Africa. METHODS: We prospectively enrolled adults, regardless of tuberculosis signs/symptoms, who were undergoing ART training from May 2007 to May 2008. After the symptom screen, patients expectorated sputum for AFB smear, tuberculosis polymerase chain reaction (PCR), and mycobacterial culture. Sensitivity and specificity of different symptoms and tests, alone and in combination, were compared with the reference standard of 6-week tuberculosis culture results. Program costs included personnel, materials, and cultures. RESULTS: Of 1035 subjects, 487 (59%) were female; median CD4 cell count was 100 cells/microL. A total of 210 subjects (20%) were receiving tuberculosis treatment and were excluded. Of the remaining 825 subjects, 158 (19%) had positive sputum cultures, of whom 14 (9%) had a positive AFB smear and 82 (52%) reported cough. The combination of cough, other symptoms, AFB smear, and chest radiograph had 93% sensitivity (95% confidence interval, 88%-97%) and 15% specificity (95% confidence interval, 13%-18%). The incremental cost of intensive screening including culture was $360 per additional tuberculosis case identified. CONCLUSIONS: Nearly 20% of patients starting ART in Durban, South Africa, had undiagnosed, culture-positive pulmonary tuberculosis. Despite WHO recommendations, neither cough nor AFB smear were adequately sensitive for screening. Tuberculosis sputum cultures should be performed before ART initiation, regardless of symptoms, in areas with a high prevalence of HIV and tuberculosis.

Integrating HIV screening into routine health care in resource-limited settings.

The United Nations is committed to achieving universal access to human immunodeficiency virus (HIV) care, treatment, and prevention. Although the gateway to HIV care and secondary prevention is knowledge of serostatus, use of voluntary counseling and testing in resource-limited settings with the highest burden of HIV infection and AIDS has been limited. On the basis of evidence of increased patient uptake and the opportunity to avoid missed HIV testing opportunities in health care facilities, in 2007, the World Health Organization recommended provider-initiated HIV testing as a standard part of medical care in settings with generalized HIV epidemics. Although provider-initiated testing has shown promise, optimal implementation strategies that ensure broad coverage, while preserving human rights, remain an active area of research. We review the benefits of knowledge of HIV serostatus and evidence from multiple countries surrounding the successes and pitfalls of provider-initiated testing in health care and home-based settings.

Home testing for HIV infection in resource-limited settings.

Among an estimated 33 million individuals who are infected with HIV worldwide, only 10% are aware of their status. HIV testing is the cornerstone to preventing further transmission and to caring for those infected, particularly as access to treatment improves in resource-limited settings. However, efforts to expand testing through facilities-based testing have not achieved adequate testing coverage, prompting efforts to reach more individuals through strategies such as home-based HIV testing. Home testing is showing promising early results in some high-prevalence, resource-limited settings. This article reviews the mechanisms and literature to date of this door-to-door approach.

HIV/AIDS: AIDS Drug Assistance Programs in the era of routine HIV testing.

AIDS [Acquired Immunodeficiency Syndrome] Drug Assistance Programs, operating within the larger Ryan White Program, are state-based, discretionary programs that provide a drug "safety net" for low-income and uninsured individuals infected with human immunodeficiency virus (HIV). Although the AIDS Drug Assistance Programs and the primary care system that provides care for patients with HIV infection are already financially stressed, the Centers for Disease Control and Prevention recently issued guidelines recommending universal HIV testing to help identify the estimated 300,000 individuals in the United States who are unaware that they are infected with HIV. As the number of people living with HIV/AIDS who are coinfected with hepatitis C virus has grown and the cost and complexity of care have increased, the sustainability of the current HIV care system requires a reevaluation in light of the new testing guidelines. We examine the current state of the AIDS Drug Assistance Programs, discuss the implications of the Centers for Disease Control and Prevention guidelines for the already overstretched Ryan White Program, and consider a federally supported national program to ensure high-quality, efficient HIV care for low-income HIV-infected Americans.