Ethical Considerations for Engaging Children and Adolescents Living with HIV in Research in African Countries: A Systematic Review.

Research engaging children and adolescents living with HIV (CALWH) is critical for youth-friendly services and HIV care, and researchers need to ensure that such engagement is ethical. We conducted a systematic review to identify key ethical considerations for the engagement of CALWH in research. The review focused on primary research articles conducted in African countries that examined ethical issues in CALWH engaged in research. Ten studies met the inclusion criteria; the following seven key domains were extracted: 1) justifications for engaging CALWH in research; 2) community involvement; 3) informed consent/assent; 4) caregiver involvement; 5) perceptions of benefits; 6) perception of the risks of involvement; and 7) confidentiality. These domains can inform the ethical engagement of CALWH in research.

Social, economic, and health effects of the COVID-19 pandemic on adolescents retained in or recently disengaged from HIV care in Kenya.

INTRODUCTION: Adolescents living with HIV (ALHIV, ages 10-19) experience complex challenges to adhere to antiretroviral therapy (ART) and remain in care, and may be vulnerable to wide-scale disruptions during the COVID-19 pandemic. We assessed for a range of effects of the pandemic on ALHIV in western Kenya, and whether effects were greater for ALHIV with recent histories of being lost to program (LTP). METHODS: ALHIV were recruited from an ongoing prospective study at 3 sites in western Kenya. The parent study enrolled participants from February 2019-September 2020, into groups of ALHIV either 1) retained in care or 2) LTP and traced in the community. Phone interviews from July 2020-January 2021 assessed effects of the pandemic on financial and food security, healthcare access and behaviors, and mental health. Responses were compared among the parent study groups. RESULTS: Phone surveys were completed with 334 ALHIV or their caregivers, including 275/308 (89.3%) in the retained group and 59/70 (84.3%) among those LTP at initial enrollment. During the pandemic, a greater proportion of LTP adolescents were no longer engaged in school (45.8% vs. 36.4%, p = 0.017). Over a third (120, 35.9%) of adolescents reported lost income for someone they relied on. In total, 135 (40.4%) did not have enough food either some (121, 36.2%) or most (14, 4.2%) of the time. More LTP adolescents (4/59, 6.8% vs. 2/275, 0.7%, p = 0.010) reported increased difficulties refilling ART. Adolescent PHQ-2 and GAD-2 scores were ≥3 for 5.6% and 5.2%, respectively. CONCLUSIONS: The COVID-19 pandemic has had devastating socioeconomic effects for Kenyan ALHIV and their households. ALHIV with recent care disengagement may be especially vulnerable. Meanwhile, sustained ART access and adherence potentially signal resilience and strengths of ALHIV and their care programs. Findings from this survey indicate the critical need for support to ALHIV during this crisis.

Dry Panels Supporting External Quality Assessment Programs for Next Generation Sequencing-Based HIV Drug Resistance Testing.

External quality assessment (EQA) is a keystone element in the validation and implementation of next generation sequencing (NGS)-based HIV drug resistance testing (DRT). Software validation and evaluation is a critical element in NGS EQA programs. While the development, sharing, and adoption of wet lab protocols is coupled with the increasing access to NGS technology worldwide, rendering it easy to produce NGS data for HIV-DRT, bioinformatic data analysis remains a bottleneck for most of the diagnostic laboratories. Several computational tools have been made available, via free or commercial sources, to automate the conversion of raw NGS data into an actionable clinical report. Although different software platforms yield equivalent results when identical raw NGS datasets are analyzed for variations at higher abundance, discrepancies arise when variations at lower frequencies are considered. This implies that validation and performance assessment of the bioinformatics tools applied in NGS HIV-DRT is critical, and the origins of the observed discrepancies should be determined. Well-characterized reference NGS datasets with ground truth on the genotype composition at all examined loci and the exact frequencies of HIV variations they may harbor, so-called dry panels, would be essential in such cases. The strategic design and construction of such panels are challenging but imperative tasks in support of EQA programs for NGS-based HIV-DRT and the validation of relevant bioinformatics tools. Here, we present criteria that can guide the design of such dry panels, which were discussed in the Second International Winnipeg Symposium themed for EQA strategies for NGS HIVDR assays.

External Quality Assessment Program for Next-Generation Sequencing-Based HIV Drug Resistance Testing: Logistical Considerations.

Next-generation sequencing (NGS) is likely to become the new standard method for HIV drug resistance (HIVDR) genotyping. Despite the significant advances in the development of wet-lab protocols and bioinformatic data processing pipelines, one often-missing critical component of an NGS HIVDR assay for clinical use is external quality assessment (EQA). EQA is essential for ensuring assay consistency and laboratory competency in performing routine biomedical assays, and the rollout of NGS HIVDR tests in clinical practice will require an EQA. In September 2019, the 2nd International Symposium on NGS HIVDR was held in Winnipeg, Canada. It convened a multidisciplinary panel of experts, including research scientists, clinicians, bioinformaticians, laboratory biologists, biostatisticians, and EQA experts. A themed discussion was conducted on EQA strategies towards such assays during the symposium. This article describes the logistical challenges identified and summarizes the opinions and recommendations derived from these discussions, which may inform the development of an inaugural EQA program for NGS HIVDR in the near future.

Online Hookup Sites for Meeting Sexual Partners Among Men Who Have Sex with Men in Rhode Island, 2013: A Call for Public Health Action.

Frequent use of websites and mobile telephone applications (apps) by men who have sex with men (MSM) to meet sexual partners, commonly referred to as "hookup" sites, make them ideal platforms for HIV prevention messaging. This Rhode Island case study demonstrated widespread use of hookup sites among MSM recently diagnosed with HIV. We present the advertising prices and corporate social responsibility (CSR) programs of the top five sites used by newly diagnosed HIV-positive MSM to meet sexual partners: Grindr, Adam4Adam, Manhunt, Scruff, and Craigslist. Craigslist offered universal free advertising. Scruff offered free online advertising to selected nonprofit organizations. Grindr and Manhunt offered reduced, but widely varying, pricing for nonprofit advertisers. More than half (60%, 26/43) of newly diagnosed MSM reported meeting sexual partners online in the 12 months prior to their diagnosis. Opportunities for public health agencies to promote HIV-related health messaging on these sites were limited. Partnering with hookup sites to reach high-risk MSM for HIV prevention and treatment messaging is an important public health opportunity for reducing disease transmission risks in Rhode Island and across the United States.

The centrality of laboratory services in the HIV treatment and prevention cascade: The need for effective linkages and referrals in resource-limited settings.

Strong laboratory services and systems are critical for delivering timely and quality health services that are vital to reduce patient attrition in the HIV treatment and prevention cascade. However, challenges exist in ensuring effective laboratory health systems strengthening and linkages. In particular, linkages and referrals between laboratory testing and other services need to be considered in the context of an integrated health system that includes prevention, treatment, and strategic information. Key components of laboratory health systems that are essential for effective linkages include an adequate workforce, appropriate point-of-care (POC) technology, available financing, supply chain management systems, and quality systems improvement, including accreditation. In this review, we highlight weaknesses of and gaps between laboratory testing and other program services. We propose a model for strengthening these systems to ensure effective linkages of laboratory services for improved access and retention in care of HIV/AIDS patients, particularly in low- and middle-income countries.

Optimal Allocation of Gold Standard Testing under Constrained Availability: Application to Assessment of HIV Treatment Failure.

The World Health Organization (WHO) guidelines for monitoring the effectiveness of HIV treatment in resource-limited settings (RLS) are mostly based on clinical and immunological markers (e.g., CD4 cell counts). Recent research indicates that the guidelines are inadequate and can result in high error rates. Viral load (VL) is considered the "gold standard", yet its widespread use is limited by cost and infrastructure. In this paper, we propose a diagnostic algorithm that uses information from routinely-collected clinical and immunological markers to guide a selective use of VL testing for diagnosing HIV treatment failure, under the assumption that VL testing is available only at a certain portion of patient visits. Our algorithm identifies the patient sub-population, such that the use of limited VL testing on them minimizes a pre-defined risk (e.g., misdiagnosis error rate). Diagnostic properties of our proposal algorithm are assessed by simulations. For illustration, data from the Miriam Hospital Immunology Clinic (RI, USA) are analyzed.

TREAT Asia Quality Assessment Scheme (TAQAS) to standardize the outcome of HIV genotypic resistance testing in a group of Asian laboratories.

The TREAT Asia (Therapeutics, Research, Education, and AIDS Training in Asia) Network is building capacity for Human Immunodeficiency Virus Type-1 (HIV-1) drug resistance testing in the region. The objective of the TREAT Asia Quality Assessment Scheme - designated TAQAS - is to standardize HIV-1 genotypic resistance testing (HIV genotyping) among laboratories to permit rigorous comparison of results from different clinics and testing centres. TAQAS has evaluated three panels of HIV-1-positive plasma from clinical material or low-passage, culture supernatant for up to 10 Asian laboratories. Laboratory participants used their standard protocols to perform HIV genotyping. Assessment was in comparison to a target genotype derived from all participants and the reference laboratory's result. Agreement between most participants at the edited nucleotide sequence level was high (>98%). Most participants performed to the reference laboratory standard in detection of drug resistance mutations (DRMs). However, there was variation in the detection of nucleotide mixtures (0-83%) and a significant correlation with the detection of DRMs (p<0.01). Interpretation of antiretroviral resistance showed approximately 70% agreement among participants when different interpretation systems were used but >90% agreement with a common interpretation system, within the Stanford University Drug Resistance Database. Using the principles of external quality assessment and a reference laboratory, TAQAS has demonstrated high quality HIV genotyping results from Asian laboratories.

Evaluation of two human immunodeficiency virus-1 genotyping systems: ViroSeq 2.0 and an in-house method.

Commercial HIV-1 genotypic resistance assays are very expensive, particularly for use in resource-constrained settings like India. Hence a cost effective in-house assay for drug resistance was validated against the standard ViroSeq HIV-1 Genotyping System 2.0 (Celera Diagnostics, CA, USA). A total of 50 samples were used for this evaluation (21 proficiency panels and 29 clinical isolates). Known resistance positions within HIV-1 protease (PR) region (1-99 codons) and HIV-1 reverse-transcriptase (RT) region (1-240 codons) were included. The results were analysed for each codon as follows: (i) concordant; (ii) partially concordant; (iii) indeterminate and (iv) discordant. A total of 2750 codons (55 codons per patient samplex50 samples) associated with drug resistance (1050 PR and 1700 RT) were analysed. For PR, 99% of the codon results were concordant and 1% were partially concordant. For RT, 99% of the codon results were concordant, 0.9% were partially concordant and 0.1% were discordant. No indeterminate results were observed and the results were reproducible. Overall, the in-house assay provided comparable results to those of US FDA approved ViroSeq, which costs about a half of the commercial assay ($ 100 vs. $ 230), making it suitable for resource-limited settings.