OBJECTIVE: To develop and assess an alternative care model using community-based care groups for PLHIV and facilitated by trained lay personnel. METHODS: Geographic locations in the Academic Model Providing Access to Healthcare Kitale clinic catchment were randomized to standard of care versus a community-based care group (ART Co-op). Adults stable on ART and virally suppressed were eligible. Research Assistant led ART Co-ops met in the community every three months. Participants were seen in the HIV clinic only if referred by study staff or by self-referral. CD4 count and viral load were measured in clinic at enrollment and after 12 months. . Retention, viral suppression, and clinic utilization were compared between groups using Chi square, Fishers exact and Wilcoxon rank sum test. RESULTS: At 12 months there were no significant differences in mean CD4 count or viral load suppression. There was a significant difference in patient retention in assigned study group between the intervention and control group (81.6% versus 98.6%; p<0.001), with a number of intervention patients withdrawing due to stigma, relocation, pregnancy, and work conflicts. All study participants, however, were retained in a HIV care program for the study duration. The median number of clinic visits was lower for the intervention group than the control group (0 vs 3; p<0.001). CONCLUSION: Individuals retained in a community-based HIV care model had clinical outcomes equivalent to those receiving clinic-based care. This innovative model of HIV care addresses the problems of insufficient healthcare personnel and patient retention barriers including time, distance, and cost to attend clinic, and has the potential for wider implementation.

BACKGROUND: Substantial efforts have been made to ensure people living with HIV (PLHIV) are linked to and retained in care but many challenges deter care utilization. We report perceived benefits of seeking HIV care and barriers to HIV care that were identified through a formative assessment conducted to advise the development of an alternative care model to deliver antiretroviral treatment therapy (ART) in Trans Nzoia County, Kenya. METHODS: Data were collected in 2015 through key informant interviews (KIIs), in-depth interviews (IDIs), and focus group discussions (FGDs). The study involved 55 participants of whom 53% were female. Ten KIIs provided community contextual information and viewpoints on the HIV epidemic in Trans Nzoia County while 20 PLHIV (10 male and 10 female) participated in IDIs. Twenty-five individuals living with HIV participated in four FGDs - two groups for men and two for women. Key informants were purposively selected, while every third patient above 18 years at the Kitale HIV Clinic was invited to share their HIV care experience through IDIs or FGDs. Trained research assistants moderated all sessions and audio recordings were transcribed and analyzed thematically. RESULTS: Findings showed that PLHIV in Trans Nzoia County used both conventional and complementary alternative care for HIV; however, public health facilities were preferred. Popular perceived benefits of adopting care were relief from symptoms and the chance to live longer. Benefits of care uptake included weight gain, renewed energy, and positive behavior change. Individual-level barriers to HIV care included lack of money and food, use of alternative care, negative side effects of ART, denial, and disclosure difficulties. At the community level, stigma, limited social support for conventional HIV treatment, and poor means of transport were reported. The health system barriers were limited supplies and staff, long distance to conventional HIV care, and unprofessional providers. CONCLUSIONS: Diverse individual, community and health system barriers continue to affect HIV care-seeking efforts in Kenya. Appreciation of context and lived experiences allows for development of realistic care models.

Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/muL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,dagger, section sign To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.

Environmental exposures have been recognized as critical in the initiation and exacerbation of asthma, one of the most common chronic childhood diseases. The National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Environmental Health Sciences (NIEHS), National Heart, Lung, and Blood Institute (NHLBI), and Merck Childhood Asthma Network (MCAN) sponsored a joint workshop to discuss the current state of the science with respect to the indoor environment and its effects on the development and morbidity of childhood asthma. The workshop included U.S. and international experts with backgrounds in allergy/allergens, immunology, asthma, environmental health, environmental exposures and pollutants, epidemiology, public health, and bioinformatics. Workshop participants provided new insights into the biologic properties of indoor exposures, indoor exposure assessment and exposure reduction techniques. This informed a primary focus of the workshop-- to critically review trials and research relevant to the prevention or control of asthma through environmental intervention. The participants identified important limitations and gaps in the scientific methodologies and knowledge, and proposed and prioritized areas for future research. The group reviewed socioeconomic and structural challenges to changing environmental exposure and offered recommendations for creative study design to overcome these challenges in trials to improve asthma management. The recommendations of this workshop can serve as guidance for future research in the study of the indoor environment and on environmental interventions as they pertain to the prevention and management of asthma and airway allergies.

The recent Ebola virus outbreak in West Africa clearly demonstrated the critical role of laboratory systems and networks in responding to epidemics. Because of the huge challenges in establishing functional laboratories at all tiers of health systems in developing countries, strengthening specimen referral networks is critical. In this review article, we propose a platform strategy for developing specimen referral networks based on 2 models: centralized and decentralized laboratory specimen referral networks. These models have been shown to be effective in patient management in programs in resource-limited settings. Both models lead to reduced turnaround time and retain flexibility for integrating different specimen types. In Haiti, decentralized specimen referral systems resulted in a 182% increase in patients enrolling in human immunodeficiency virus treatment programs within 6 months. In Uganda, cost savings of up to 62% were observed with a centralized model. A platform strategy will create a network effect that will benefit multiple disease programs.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(dagger) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

Guidelines for antiretroviral (ARV) prophylaxis following high-risk exposure (postexposure prophylaxis—PEP) to human immunodeficiency virus (HIV) date to 1990, when the US Centers for Disease Control and Prevention (CDC) first considered such recommendations for persons with occupational exposures to HIV [1]. The US Public Health Service also issued recommendations focused on occupational exposures in 1996 [2]; these recommendations have been updated 5 times [3–7]. Prophylaxis after non-occupational exposures to HIV (via sexual contact and sharing of drug-using paraphernalia) was first addressed by the CDC in 1998 [8] and updated in 2005 [9]. The World Health Organization (WHO) first considered PEP in 2007 and included PEP recommendations in the 2013 consolidated guidelines; both documents focused on occupational exposures [10, 11]. The most recently published WHO guidelines on PEP recommend that a PEP regimen be administered as soon as possible within the 72-hour window period after an HIV-related exposure and that whereas a 2-drug antiretroviral regimen is acceptable, a 3-drug regimen is preferred [12].

BACKGROUND: During 2004-2009, >12,000 children (<15 years old) initiated antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes and temporal trends in outcomes were investigated. METHODS: Rates of death, loss to follow-up (LTFU), and attrition (death or LTFU) were evaluated in a nationally representative sample of 1,054 children, who initiated ART during 2004-2009 at 25 facilities randomly selected using probability-proportional-to-size sampling. RESULTS: At ART initiation during 2004-2009, 50% were male, median age was 3.3 years, median CD4% was 13%, median CD4 count was 375 cells/microL, and median weight-for-age z-score was -2.1. During 2004-2009, median time from HIV diagnosis to care initiation declined from 33 to 0 days (p=0.001), median time from care to ART declined from 93 to 62 days (p=0.004), the percentage aged <2 at ART initiation increased from 16% to 48% (p=0.021), the percentage of patients with prior tuberculosis declined from 50% to 10% (p=0.009), and the percentage with prior lymphocytic interstitial pneumonia declined from 16% to 1% (p<0.001). Over 2,652 person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition was 11% overall, but increased from 3% to 22% during 2004-2009, due mainly to increases in 12-month LTFU (from 3% to 18%). CONCLUSION: Declines in the prevalence of markers of advanced HIV disease at ART initiation probably reflect increasing ART access. However, 12-month LTFU increased during program expansion, and this negated any program improvements in outcomes that might have resulted from earlier ART initiation.

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/mul over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/mul, bias ranged from -35.2 to +13.1 cells/mul while at counts >350 cells/mul, bias ranged from -70.7 to +47 cells/mul, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/mul ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.

Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by age at enrollment: adolescents and young adults (aged 15-24 years), middle-aged adults (aged 25-49 years), and older adults (aged ≥50 years). Enrollees aged 15-24 years were predominantly female (81%-92%), commonly pregnant (3%-32% of females), unmarried (54%-73%), and, in four countries with employment data, unemployed (53%-86%). In comparison, older adults were more likely to be male (p<0.001), employed (p<0.001), and married, (p<0.05 in five countries). Compared with older adults, adolescents and young adults had higher LTFU rates in all seven countries, reaching statistical significance in three countries in crude and multivariable analyses. Evidence-based interventions to reduce LTFU for adolescent and young adult ART enrollees could help reduce mortality and HIV incidence in this age group.

In the article by Greig et al1 from Médecins sans Frontières, the authors compared data from their supported HIV/AIDS care and treatment programs at 17 sites in 9 countries in sub-Saharan Africa. Initially, their support began as vertical programs, but later they changed to an integrated model that incorporated HIV treatment into general health care services. In this retrospective study (2003–2010), they compared a number of clinical indicators of antiretroviral treatment (ART) outcome, although controlling for a variety of potential confounders. However, a major potential confounder, CD4 count at initiation of ART, was not included due to 30% with missing data. The study included 14,124 patients at 7 vertical program sites and 1279 at 10 integrated sites. All of the integrated sites were rural, whereas 4 of 7 vertical sites were urban. Programs were standardized across both program types. Training and advisory staff were similar for both. A standardized electronic database containing routinely collected data facilitated this study. Follow-up data were censored at 30 months on ART to make the follow-up time equal between the 2 programs. | Although the authors used data collected from a large number of sites in multiple countries, they examined only retrospective data and were unable to address specific country contexts and the relative costs of the 2 approaches. However, the study results add useful information to the small body of studies that evaluate the utility of integrated programs compared with vertical programs.

Estimation of HIV-1 incidence is an important public health tool for understanding the status of the epidemic, identifying high-risk populations, and assessing various intervention strategies. Several laboratory-based methods have been developed for distinguishing recent from long-term HIV-1 infection; however, each exhibits some degree of misclassification, particularly among AIDS patients and those taking antiretroviral therapy (ART). To improve upon the limitations associated with measuring responses to a single analyte, we have developed a bead-based, multiplex assay for determination of HIV recent infection based on total antibody binding and antibody avidity to multiple analytes. An HIV-specific, multiplex panel was created by coupling the recombinant HIV-1 proteins p66, gp120, gp160, and gp41 to Bio-Plex COOH microspheres. Longitudinal plasma specimens from recent seroconverters were tested for reactivity to the coupled microspheres using the Bio-Plex 200 System. For each analyte, HIV-specific antibody binding and avidity increased for 1-2 years post-seroconversion, leading to a significant difference in reactivity between recent and long-term specimens. While the potential for misclassification of individuals diagnosed with AIDS or receiving antiretroviral therapy appears to be minimal with avidity measures, the impact on total antibody binding was variable, depending on the individual analyte. This bead-based, HIV-specific multiplex assay measures several distinct immune responses in a single assay plate, allowing for sampling of multiple analytes in the determination of recent infection, which could aid in the development of improved statistical methods or algorithms that will more accurately estimate HIV incidence.

Quality assurance (QA) is a systematic process to monitor and improve clinical laboratory practices. The fundamental components of a laboratory QA program include providing a functional and safe laboratory environment, trained and competent personnel, maintained equipment, adequate supplies and reagents, testing of appropriate specimens, internal monitoring of quality, accurate reporting, and external quality assessments. These components are necessary to provide accurate and precise CD4 T-cell counts, an essential test to evaluate start of and monitor effectiveness of antiretroviral therapy for HIV-infected patients. In recent years, CD4 testing has expanded dramatically in resource-limited settings. Information on a CD4 QA program as described in this article will provide guidelines not only for clinical laboratory staff but also for managers of programs responsible for supporting CD4 testing. All agencies involved in implementing CD4 testing must understand the needs of the laboratory and provide advocacy, guidance, and financial support to established CD4 testing sites and programs. This article describes and explains the procedures that must be put in place to provide reliable CD4 determinations in a variety of settings.