Background: Diarrhea is an important health problem among HIV-infected patients. This study evaluated the role of HIV in the epidemiology, etiology, and severity of diarrheal disease among children. Methods: The Global Enteric Multicenter Study enrolled children with moderate-to-severe diarrhea (MSD) and less-severe diarrhea (LSD) between December 2007 and November 2012. One to three controls for MSD cases and one per LSD case were enrolled and matched by age, sex, and neighborhood. All children were tested for HIV. Clinical data, anthropometric data, and stool samples were collected. Follow-up was performed at 60 days. Results: Two hundred and fourteen MSD cases and 418 controls, together with 349 LSD cases and 214 controls were tested. HIV prevalence was 25% among MSD cases (4% for matched controls) and 6% among LSD cases (6% among matched controls). HIV-infected children were more likely to have MSD (odds ratio 5.6, p < 0.0001). Mortality rates were higher among HIV-infected children than among the uninfected (34 vs. 5 per 1000 child-weeks at risk; p = 0.0039). Cryptosporidium, Giardia, and enteroaggregative Escherichia coli (aatA only) were more prevalent among HIV-infected MSD cases than among uninfected ones. Conclusion: HIV is an important risk factor for MSD. The high mortality rate implies that children with MSD should be screened for HIV and managed accordingly. © 2018 The Author(s)

Several different assay methodologies have been described for the evaluation of HIV or SIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC). Commonly used assays measure ADCC by evaluating effector cell functions, or by detecting elimination of target cells. Signaling through Fc receptors, cellular activation, cytotoxic granule exocytosis, or accumulation of cytolytic and immune signaling factors have been used to evaluate ADCC at the level of the effector cells. Alternatively, assays that measure killing or loss of target cells provide a direct assessment of the specific killing activity of antibodies capable of ADCC. Thus, each of these two distinct types of assays provides information on only one of the critical components of an ADCC event; either the effector cells involved, or the resulting effect on the target cell. We have developed a simple modification of our previously described high-throughput ADCC GranToxiLux (GTL) assay that uses area scaling analysis (ASA) to facilitate simultaneous quantification of ADCC activity at the target cell level, and assessment of the contribution of natural killer cells and monocytes to the total observed ADCC activity when whole human peripheral blood mononuclear cells are used as a source of effector cells. The modified analysis method requires no additional reagents and can, therefore, be easily included in prospective studies. Moreover, ASA can also often be applied to pre-existing ADCC-GTL datasets. Thus, incorporation of ASA to the ADCC-GTL assay provides an ancillary assessment of the ability of natural and vaccine-induced antibodies to recruit natural killer cells as well as monocytes against HIV or SIV; or to any other field of research for which this assay is applied. Copyright 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC. Copyright 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.

Background: Implementation research (IR) facilitates health systems strengthening and optimal patient outcomes by generating evidence for scale-up of efficacious strategies in context. Thus, difficulties in generating IR evidence, particularly in limited-resource settings with wide disease prevention and treatment gaps, need to be anticipated and addressed. Nigeria is a priority country for the prevention of mother-to-child transmission of HIV (PMTCT). This paper analyses the experiences of four PMTCT IR studies in Nigeria, and proffers solutions to major challenges encountered during implementation. Studies included and findings: Multicentre PMTCT IR studies conducted in Nigeria during the Global Plan's assessment period (2011 to 2015) were included. Four studies were identified, namely The Baby Shower Trial, Optimizing PMTCT, MoMent and Lafiyan Jikin Mata. Major common challenges encountered were categorised as 'External' (beyond the control of study teams) and 'Internal' (amenable to rectification by study teams). External challenges included healthcare worker strikes and turnover, acts and threats of ethnic and political violence and terrorism, and multiplicity of required local ethical reviews. Internal challenges included limited research capacity among study staff, research staff turnover and travel restrictions hindering study site visits. Deliberate research capacity-building was provided to study staff through multiple opportunities before and during study implementation. Post-study employment opportunities and pathways for further research career-building are suggested as incentives for study staff retention. Engagement of study community-resident personnel minimised research staff turnover in violence-prone areas. Conclusions: The IR environment in Nigeria is extremely diverse and challenging, yet, with local experience and anticipatory planning, innovative solutions can be implemented to modulate internal challenges. Issues still remain with healthcare worker strikes and often unpredictable insecurity. There is a dire need for cooperation between institutional review boards across Nigeria in order to minimise the multiplicity of reviews for multicentre studies. External challenges need to be addressed by high-level stakeholders, given Nigeria's crucial regional and global position in the fight against the HIV epidemic. Copyright 2018 The Author(s).

Background: HIV status disclosure to male partners is important for optimal outcomes in the prevention of mother-to-child transmission of HIV (PMTCT). Depending on timing of HIV diagnosis or pregnancy status, readiness to disclose and disclosure rates may differ among HIV-positive women. We sought to determine rates, patterns, and experiences of disclosure among Nigerian women along the PMTCT cascade. Methods: HIV-positive women in rural North-Central Nigeria were purposively recruited according to their PMTCT cascade status: pregnant-newly HIV-diagnosed, pregnant-in care, postpartum, and lost-to-follow-up (LTFU). Participants were surveyed to determine rates of disclosure to male partners and others; in-depth interviews evaluated disclosure patterns and experiences. Tests of association were applied to quantitative data. Qualitative data were manually analysed by theme and content using the constant comparative method in a Grounded Theory approach. Results: We interviewed 100 women; 69% were 21-30 years old, and 86% were married. There were 25, 26, 28 and 21 women in the newly-diagnosed, in-care, postpartum, and LTFU groups, respectively. Approximately 81% of all participants reported disclosing to anyone; however, family members were typically disclosed to first. Ultimately, more women had disclosed to male partners (85%) than to family members (55%). Rates of disclosure to anyone varied between groups: newly-diagnosed and LTFU women had the lowest (56%) and highest (100%) rates, respectively (p = 0.001). However, family (p = 0.402) and male partner (p = 0.218) disclosure rates were similar between cascade groups. Across all cascade groups, fear of divorce and intimate partner violence deterred women from disclosing to male partners. However, participants reported that with assistance from healthcare workers, disclosure and post-disclosure experiences were mostly positive. Conclusion: In our study cohort, although disclosure to male partners was overall higher, family members appeared more approachable for initial disclosure. Across cascade groups, male partners were ultimately disclosed to at rates > 75%, with no significant inter-group differences. Fear appears to be a major reason for non-disclosure or delayed disclosure by women to male partners. Augmentation of healthcare workers' skills and involvement can mediate gender power differentials, minimize fear and shorten time to male partner disclosure among women living with HIV, regardless of their PMTCT cascade status. Trial registration: Clinicaltrials.gov registration number NCT 01936753, September 3, 2013 (retrospectively registered). Copyright 2018 The Author(s).

Introduction Surveillance of HIV drug resistance (HIVDR) is crucial to ensuring the continued success of antiretroviral therapy (ART) programs. With the concern of reduced genotyping sensitivity of HIV on dried blood spots (DBS), DBS for HIVDR surveillance have been limited to ART-naïve populations. To investigate if DBS under certain conditions may also be a feasible sample type for HIVDR testing in ART patients, we piloted nationwide surveys for HIVDR among ART patients using DBS in two African countries with rapid scale-up of ART. Methods EDTA-venous blood was collected to prepare DBS from adult and pediatric ART patients receiving treatment during the previous 12-36 months. DBS were stored at ambient temperature for two weeks and then at -80C until shipment at ambient temperature to the WHO-designated Specialized HIVDR Laboratory at CDC in Atlanta. Viral load (VL) was determined using NucliSENS ® HIV-1 v2.0 kits; HIVDR genotyping was performed using the ATCC HIV-1 Drug Resistance Genotyping kits. Results DBS were collected from 1,368 and 1,202 ART patients; 244 and 255 these specimens had VL 1,000 copies/mL in Kenya and Tanzania, respectively. The overall genotyping rate of those DBS with VL 1,000 copies/mL was 93.0% (95% CI: 89.1%-95.6%) in Kenya and 91.8% (87.7%-94.6%) in Tanzania. The turnaround times for the HIVDR surveys from the time of collecting DBS to completing laboratory testing were 6.5 months and 9.3 months for the Kenya and Tanzania surveys, respectively. Conclusions The study demonstrates a favorable outcome of using DBS for nationwide surveillance of HIVDR in ART patients. Our results confirm that DBS collected and stored at ambient temperature for two weeks, and shipped with routine courier services are a reliable sample type for large-scale surveillance of acquired HIVDR. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

BACKGROUND: In HIV programs, mentor mothers (MMs) are women living with HIV who provide peer support for other women to navigate HIV care, especially in the prevention of mother-to-child transmission of HIV (PMTCT). Nigeria has significant PMTCT program gaps, and in this resource-constrained setting, lay health workers such as MMs serve as task shifting resources for formal healthcare workers and facility-community liaisons for their clients. However, challenging work conditions including tenuous working relationships with healthcare workers can reduce MMs' impact on PMTCT outcomes. This study explores the experiences and opinions of MMs with respect to their work conditions and relationships with healthcare workers. METHODS: This study was nested in the prospective two-arm Mother Mentor (MoMent) study, which evaluated structured peer support in PMTCT. Thirty-six out of the 38 MMs who were ever engaged in the MoMent study were interviewed in seven focus group discussions, which focused on MM workload and stipends, scope of work, and relationships with healthcare workers. English and English-translated Hausa-language transcripts were manually analyzed by theme and content in a grounded theory approach. RESULTS: Both intervention and control-arm MMs reported positive and negative relationships with healthcare workers, modulated by individual healthcare worker and structural factors. Issues with facility-level scope of work, workplace hierarchy, exclusivism and stigma/discrimination from healthcare workers were discussed. MMs identified clarification, formalization, and health system integration of their roles and services as potential mitigations to tenuous relationships with healthcare workers and challenging working conditions. CONCLUSIONS: MMs function in multiple roles, as task shifting resources, lay community health workers, and peer counselors. MMs need a more formalized, well-defined niche that is fully integrated into the health system and is responsive to their needs. Additionally, the definition and formalization of MM roles have to take healthcare worker orientation, sensitization, and acceptability into consideration.

Introduction: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. Methods: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-Analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low-And middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. Results and discussion: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. Conclusions: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS. Copyright 2017 Haberer JE et al.

Patients with perinatally acquired HIV may be at risk for the development of age-related non-AIDS diseases. The primary aim of this study was to describe patterns of systemic hypertension among a cohort of adults (≥18 years) with perinatally acquired HIV. A retrospective cohort study was conducted among adults (≥18 years) with perinatally acquired HIV infection. Primary outcomes included documentation of systemic hypertension as well as several additional non-AIDS-associated illnesses. Systemic hypertension incidence rates and rate ratios (RRs) were calculated among groups aged ≥18 and <18 years at the time of hypertension diagnosis. The overall prevalence of hypertension in the cohort (N = 109) was 26.6%, and the incidence rate of hypertension was significantly higher among those aged ≥18 years compared to those who are aged <18 years at the time of diagnosis (RR: 10.0, CI: 7.29-13.71). By multivariable analysis, only coexisting renal disease was associated with an increased risk of hypertension diagnosis. Copyright The Author(s) 2016.

Introduction: In patients with hepatitis C virus (HCV), human immunodeficiency virus (HIV) represents a major cause of morbidity and economic burden. Economic evaluations in HIV-HCV typically focus on government-sponsored insurance plans rather than a commercially insured cohort. This study evaluated the clinical and economic burden of HIV-HCV co-infection compared with HCV alone in commercially insured patients throughout the United States. Methods: Commercial medical and pharmacy claims from 2007 to 2015 from a 10% random sample of enrollees within the IQVIA PharMetrics Plus™ administrative claims database were analyzed. Patients were included based on the presence of a claim with a HCV diagnosis across three separate cross-sectional periods which were created from the full dataset (2007–2009, 2010–2012, and 2013–2015). Costs incurred were categorized as emergency department, inpatient, outpatient medical, outpatient pharmacy, and other, based on the claim place of service. Descriptive statistics and proportion of total costs in each group have been reported for all cost categories. Results: The samples included 22,329 from 2007 to 2009, 23,186 from 2010 to 2012, and 27,288 from 2013 to 2015. In all three cross-sections, HIV-HCV individuals were more likely to be male and carriers of hepatitis B virus. Pharmacy costs were $29,368 in the HCV-only group, compared to $73,547 in the HIV-HCV group (p < 0.0001). Pharmacy costs increased as a proportion of total costs for both groups, increasing after 2012 from 41% to 55% for HIV-HCV and from 19% to 34% for HCV-only. Conclusion: The present study describes the total direct health care costs in HIV-HCV co-infected individuals and HCV-only patients in commercially insured health plans. Spending on pharmacy increased as a proportion of total health care costs in both groups. Further clinical and economic evaluations in HCV and/or HIV populations in the US should consider system-level factors related to insurance type when applying to the entire population. Copyright 2019, The Author(s).

Background: Adolescents living with HIV (ALHIV) have worse health outcomes than other populations of people living with HIV. Contributing factors include lack of standard and comprehensive procedures for ALHIV transitioning from pediatric to adult care. This has contributed to poor retention at, and following transition, which is problematic especially in high ALHIV-burden, resource-limited settings like Nigeria. Methods: Using a two-arm cluster randomized control design, the Adolescent Coordinated Transition (ACT) trial will measure the comparative effectiveness of a graduated transition and organized support group intervention against the usual practice of abrupt transfer of Nigerian ALHIV from pediatric to adult care. This study will be conducted at 12 secondary and tertiary healthcare facilities (six intervention, six control) across all six of Nigeria's geopolitical zones. The study population is 13- to 17-year-old ALHIV (N = 216, n = 108 per study arm) on antiretroviral therapy. Study participants will be followed through a 12-month pre-transfer/transition period and for an additional 24 months post transfer/transition. The primary outcome measure is the proportion of ALHIV retained in care at 12 and 24 months post transfer. Secondary outcome measures are proportions of ALHIV achieving viral suppression and demonstrating increased psychosocial wellbeing and self-efficacy measured by psychometric tests including health locus of control, functional social support, perceived mental health, and sexual risk and behavior. Discussion: We hypothesize that the ACT intervention will significantly increase psychosocial wellbeing, retention in care and ultimately viral suppression among ALHIV. ACT's findings have the potential to facilitate the development of standard guidelines for transitioning ALHIV and improving health outcomes in this population. The engagement of a consortium of local implementing partners under the Nigeria Implementation Science Alliance allows for nationwide study implementation and expedient results dissemination to program managers and policy-makers. Ultimately, ACT may also provide evidence to inform transitioning guidelines not only for ALHIV but for adolescents living with other chronic diseases in resource-limited settings. Trial registration: ClinicalTrials.gov, ID: NCT03152006. Registered on May 12, 2017. Copyright 2017 The Author(s).