Nigeria is one of six countries with half the global burden of youth living with HIV. Interventions to date have been inadequate as AIDS-related deaths in Nigeria's youth have remained unchanged in ...recent years. The iCARE Nigeria HIV treatment support intervention, a combination of peer navigation and SMS text message medication reminders to promote viral suppression, demonstrated initial efficacy and feasibility in a pilot trial among youth living with HIV in Nigeria. This paper describes the study protocol for the large-scale trial of the intervention.
The iCARE Nigeria-Treatment study is a randomized stepped wedge trial of a combination (peer navigation and text message reminder) intervention, delivered to youth over a period of 48 weeks to promote viral suppression. Youth receiving HIV treatment at six clinical sites in the North Central and South Western regions of Nigeria were recruited for participation. Eligibility criteria included registration as a patient at participating clinics, aged 15-24 years, on antiretroviral therapy for at least three months, ability to understand and read English, Hausa, Pidgin English, or Yoruba, and intent to remain a patient at the study site during the study period. The six clinic sites were divided into three clusters and randomized to a sequence of control and intervention periods for comparison. The primary outcome is plasma HIV-1 viral load suppression, defined as viral load ≤ 200 copies/mL, in the intervention period versus the control period at 48 weeks of intervention.
Evidence-based interventions to promote viral load suppression among youth in Nigeria are needed. This study will determine efficacy of a combination intervention (peer navigation and text message reminder) and collect data on potential implementation barriers and facilitators to inform scale-up if efficacy is confirmed.
ClinicalTrials.gov number, NCT04950153, retrospectively registered July 6, 2021, https://clinicaltrials.gov/.
Introduction
Adolescents are a unique and sometimes neglected group in the planning of healthcare services. This is the case in many parts of sub‐Saharan Africa, where more than eight out of ten of ...the world's HIV‐infected adolescents live. Although the last decade has seen a reduction in AIDS‐related mortality worldwide, largely due to improved access to effective antiretroviral therapy (ART), AIDS remains a significant contributor to adolescent mortality in sub‐Saharan Africa. Although inadequate access to ART in parts of the subcontinent may be implicated, research among youth with HIV elsewhere in the world suggests that suboptimal adherence to ART may play a significant role. In this article, we summarize the epidemiology of HIV among sub‐Saharan African adolescents and review their adherence to ART, emphasizing the unique challenges and factors associated with adherence behaviour.
Methods
We conducted a comprehensive search of online databases for articles, relevant s, and conference reports from meetings held between 2010 and 2014. Our search terms included “adherence,” “compliance,” “antiretroviral use” and “antiretroviral adherence,” in combination with “adolescents,” “youth,” “HIV,” “Africa,” “interventions” and the MeSH term “Africa South of the Sahara.” Of 19,537 articles and s identified, 215 met inclusion criteria, and 148 were reviewed.
Discussion
Adolescents comprise a substantial portion of the population in many sub‐Saharan African countries. They are at particular risk of HIV and may experience worse outcomes. Although demonstrated to have unique challenges, there is a dearth of comprehensive health services for adolescents, especially for those with HIV in sub‐Saharan Africa. ART adherence is poorer among older adolescents than other age groups, and psychosocial, socio‐economic, individual, and treatment‐related factors influence adherence behaviour among adolescents in this region. With the exception of a few examples based on affective, cognitive, and behavioural strategies, most adherence interventions have been targeted at adults with HIV.
Conclusions
Although higher levels of ART adherence have been reported in sub‐Saharan Africa than in other well‐resourced settings, adolescents in the region may have poorer adherence patterns. There is substantial need for interventions to improve adherence in this unique population.
In this randomized pilot clinical trial, dolutegravir plus lamivudine was noninferior to continuation of standard 3-drug maintenance antiretroviral therapy. There was no emergence of drug resistance ...in the participant who experienced virologic failure while receiving dolutegravir plus lamivudine.
Africa is the second most populous continent and has perennial health challenges. Of the estimated 181 million school aged children in sub-Saharan Africa (SSA), nearly half suffer from ascariasis, ...trichuriasis, or a combination of these infections. Coupled with these is the problem of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection, which is a leading cause of death in the region. Compared to the effect of the human immunodeficiency virus on the development of TB, the effect of chronic helminth infections is a neglected area of research, yet helminth infections are as ubiquitous as they are varied and may potentially have profound effects upon host immunity, particularly as it relates to TB infection, diagnosis, and vaccination. Protection against active TB is known to require a clearly delineated T-helper type 1 (Th1) response, while helminths induce a strong opposing Th2 and immune-regulatory host response. This Review highlights the potential challenges of helminth-TB co-infection in Africa and the need for further research.
Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine.
A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) ...plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA ≥1000 and <500000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was the proportion with HIV-1 RNA <50 copies/mL (FDA US Food and Drug Administration Snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20 or >200 copies/mL at or after week 24. Dolutegravir levels and drug resistance testing were performed at VF.
One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA >100000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm3. Virologic efficacy at week 24 was 108/120 (90%, confidence interval 83%, 95%), with comparable results in the >100000 copies/mL and ≤100000 copies/mL strata, that is, 89% (75%, 97%) and 90% (82%, 96%), respectively. Three participants with VF, had undetected plasma dolutegravir at ≥1 time points; the M184V and R263R/K mutations developed in 1 participant. Two participants experienced grade 3 possible/probable treatment-related adverse events; none discontinued treatment due to adverse events.
Dolutegravir plus lamivudine demonstrated efficacy in individuals with pretreatment HIV-1 RNA up to 500000 copies/mL in this pilot trial, but a participant developed resistance mutations.
NCT02582684.
With advances in HIV treatment, people with HIV (PWH) are living longer but experience aging-related comorbidities, including cognitive deficits, at higher rates than the general population. Previous ...studies have shown alterations in lysosomal proteins in blood from PWH with severe dementia. However, these markers have not been evaluated in PWH with milder neurocognitive impairment. We sought to determine whether levels of the lysosomal cysteine protease cathepsin B (CatB) and its endogenous inhibitor cystatin B (CysB) were altered in PWH with neurocognitive impairment and whether antiretroviral therapy (ART) further influenced these levels. Peripheral blood mononuclear cells were obtained from the tenofovir arm of a multicenter clinical trial in which ART-naive, HIV+ participants received treatment for 48 weeks (ACTG A5303, NCT01400412). PWH were divided by neurocognitive status (eg, with or without neurocognitive impairment) before ART initiation. Intracellular levels of CatB and CysB were measured in T cells and monocytes by means of flow cytometry. Levels of CysB were significantly decreased in both CD4 + T cells and CD8 + T cells after 48 weeks of ART in HIV+ participants without neurocognitive impairment but not in participants with neurocognitive impairment. Levels of CysB were increased in CD14 + monocytes from the participants with neurocognitive impairment after ART. Levels of CysB and CatB positively correlated regardless of HIV, neurocognitive status, or exposure to ART. These findings suggest that CysB has the potential to provide mechanistic insight into HIV-associated neurocognitive disorders or provide a molecular target for systemic monitoring or treatment of neurocognitive impairment in the context of ART and should be investigated further.
Disparities in SARS-CoV-2 genomic surveillance have limited our understanding of the viral population dynamics and may delay identification of globally important variants. Despite being the most ...populated country in Africa, Nigeria has remained critically under sampled. Here, we report sequences from 378 SARS-CoV-2 isolates collected in Oyo State, Nigeria between July 2020 and August 2021. In early 2021, most isolates belonged to the Alpha "variant of concern" (VOC) or the Eta lineage. Eta outcompeted Alpha in Nigeria and across West Africa, persisting in the region even after expansion of an otherwise rare Delta sub-lineage. Spike protein from the Eta variant conferred increased infectivity and decreased neutralization by convalescent sera in vitro. Phylodynamic reconstructions suggest that Eta originated in West Africa before spreading globally and represented a VOC in early 2021. These results demonstrate a distinct distribution of SARS-CoV-2 lineages in Nigeria, and emphasize the need for improved genomic surveillance worldwide.
The advent of combination antiretroviral therapy (ART) has significantly decreased AIDS-related morbidity and mortality. Nevertheless, the benefits of ART are only realized through adherence to ...lifelong treatment. Though contemporary antiretroviral (ARV) drugs have fewer adverse effects in comparison to older ARV drugs, many agents are associated with negative or unknown long-term effects. There is increasing evidence that two-drug (dual-therapy) regimens may be an effective alternative to the currently recommended three-drug (triple-therapy) regimens. In this review, we provide a comprehensive and critical review of recently completed and ongoing trials of dual-therapy regimens in treatment-naïve and treatment-experienced HIV-1-infected patients. We also review current HIV/AIDS society recommendations regarding dual therapy as well as future therapeutic possibilities.
With the second-generation integrase inhibitors (dolutegravir and bictegravir) extending the attributes of earlier integrase inhibitors, three-drug regimens containing integrase inhibitors plus two ...nucleos(t)ide reverse transcriptase inhibitors are now widely recommended for first-line (initial) treatment of human immunodeficiency virus-1 infection. Led by dolutegravir plus lamivudine, two-drug therapy is emerging as a way to reduce antiretroviral therapy cost and adverse effects without compromising treatment options should virologic failure occur. Initial two-drug therapy has limitations, including the relative incompatibility with the coemerging concept of same-day antiretroviral therapy initiation.
Purpose of Review
Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. ...Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals.
Recent Findings
Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development. Long-acting modalities in earlier development stages employ drug-loaded implants, microparticles, or targeted mutagenesis, among other innovations.
Summary
Long-acting antiretroviral drugs promise new options for HIV prevention and treatment, and ways to address poor adherence and treatment fatigue. Further studies will identify the long-acting agents or combinations that are suitable for routine use. Creative solutions will be needed for anticipated implementation challenges.
PDF
