Realist evaluation of a community-based antiretroviral therapy (CBART) programme for key populations in Benue State in Nigeria.

BACKGROUND: World Health Organization recommended community-based ART (CBART) approaches to improve access to antiretroviral treatment (ART) and treatment outcomes among key populations living with (KPLHIV). Key populations (KP) are female sex workers, men who have sex with men, persons who inject drugs, and transgender people. How CBART for KP (KP-CBART) worked and why, for whom and in what circumstances it worked within KP communities or at community sites, are yet to be described. The aim of this study is to describe the different KP-CBART approaches or models in Nigeria, identifying the context conditions and mechanisms that are likely to produce the desired outcomes. METHOD: Building on our previous study eliciting an initial programme theory for KP-CBART, we used a multiple case design and cross-case analysis to evaluate 3 KP-CBART approaches, namely: One Stop Shop clinic; community drop-in centre; and outreach venue. Between 2021 and 2023, we conducted a retrospective cohort study, 99 indepth interviews and 5 focused group discussions with various actors. Using realist evaluation, we synthesised context-mechanism-outcome configurations (CMOCs) and developed programme theory for each of the cases and an overall theory. RESULT: The analysis showed the central importance of decentralizing ART service delivery to a safe place within the community for KPLHIV. The provision of ART in a KP friendly environment triggered a feeling of safety and trust in the healthcare workers among KPLHIV, resulting in KP-CBART acceptance and improved ART uptake, medication adherence and retention on ART. KP community engagement in ART delivery, peer support through support group meetings, and linkages with KP-led organizations improved self-efficacy, fostered solidarity and a sense of belonging among KP. These resources encouraged and motivated clients to engage with the KP-CBART model. However, fear of disclosure of HIV and KP status, and lack of trust between KP groups, demotivated and discouraged KPLHIV from initiating ART and continuing their treatment in KP-CBART. CONCLUSION: To optimise access to ART and treatment outcomes for KPLHIV, policy makers and health practitioners should ensure the provision of a safe place for ART service delivery that can be trusted by the clients and the KP communities.

Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines.

The development of broadly neutralizing antibody (bnAb)-based therapeutic HIV-1 vaccines and cure concepts depends on monitoring bnAb plasma activity in people with HIV (PWH) on suppressive antiretroviral therapy (ART). To enable this, analytical strategies must be defined to reliably distinguish antibody-based neutralization from drug inhibition. Here, we explore strategies that either utilize drug-resistant viruses or remove drugs from plasma. We develop ART-DEX (ART dissociation and size exclusion), an approach which quantitatively separates drugs from plasma proteins following pH-triggered release allowing accurate definition of antibody-based neutralization. We demonstrate that ART-DEX, alone or combined with ART-resistant viruses, provides a highly effective and scalable means of assessing antibody neutralization during ART. Implementation of ART-DEX in standard neutralization protocols should be considered to enhance the analytical capabilities of studies evaluating bnAb therapeutics and therapeutic vaccines, furthering the development of advanced ART and HIV-1 cure strategies.

Relationship between Modern ART Regimens and Immunosenescence Markers in Patients with Chronic HIV Infection.

The increased life expectancy of PLHIV (People Living with HIV) and the successful highly combined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection "accelerates" aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterized by inflammation and immune activation that persists despite cART, and that may contribute to the development of co-morbid conditions. In this regard, we aimed to compare current cART regimens in light of premature aging to evaluate differences in their ability to reduce immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1ß, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and affordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show a less favorable regimen profile containing a protease inhibitor. Our data suggest an incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the interest in various biomarkers related to immune activation and inflammation as predictors of clinical outcomes among PLHIV will increase in the future.

Phylogenetic Network Analyses Reveal the Influence of Transmission Clustering on the Spread of HIV Drug Resistance in Quebec from 2002 to 2022.

BACKGROUND: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. METHODS: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced (n = 3500) and ART-naïve persons (n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- (n = 1577) and post-ART experience (n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2-5, vs. 6+ members per cluster as categorical variables. RESULTS: Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007-2011, 2012-2016, and 2017-2022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14-73 IQR) and 16 (9-26 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1-2%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-naïve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies/mL, respectively (p < 0.0001). CONCLUSION: Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR.

Antiretroviral therapy adherence among peripartum women with HIV in Kenya: an explanatory mixed methods study using dry blood spot measures and narrative interviews.

ABSTRACTAdherence to antiretroviral therapy (ART) remains sub-optimal among pregnant and postpartum women with HIV (PPWH) in high HIV prevalence low resource settings with few effective behavioral interventions. A large body of qualitative literature has established general barriers and facilitators to ART adherence in PPWH at various levels (individual, interpersonal, structural). However, research exploring the underlying behavioral mechanisms of ART adherence in PPWH with objectively verified adherence biomarkers is extremely limited. We conducted 24 in-depth interviews with postpartum women in western Kenya who had linked ART drug concentrations obtained from three dried blood spot samples across the peripartum period. Among PPWH with a low drug concentration (n = 13) compared to those with continuously high drug concentrations (n = 11), distinct themes emerged related to HIV status disclosure, social support, interactions with the health system, and health beliefs. By combining ART biomarkers with patient reported challenges, there is the potential for real-time interventions to support sustained ART adherence among PPWH and improve maternal and infant health outcomes.

No increased risk of tuberculosis-related immune reconstitution inflammatory syndrome with integrase inhibitor-based antiretroviral therapy in people with HIV with profound immunosuppression.

INTRODUCTION: The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis-related immune reconstitution inflammatory syndrome (TB-IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB-HIV initiating antiretroviral therapy (ART) in Hong Kong. METHODS: This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. RESULTS: Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0-32.7) and 14 of 63 patients (22.2%; 95% CI 12.0-32.5) from the INSTI and non-INSTI groups experienced TB-IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0-7.8] vs. 4 weeks [IQR 2.0-5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS-related death in either group. The risk of TB-IRIS with INSTI versus non-INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 µL (10/33 [30.3%; 95% CI 14.6-46.0] vs. 10/22 [45.5%; 95% CI 24.7-66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti-TB treatment (10/26 [38.5%; 95% CI 19.8-57.2] vs. 10/23 [43.5%; 95% CI 23.2-63.7], p = 0.721). CONCLUSION: Our cohort study did not offer support for an increased risk of TB-IRIS with INSTIs compared with non-INSTIs, even in severely immunocompromised people with HIV.

Opportunistic infections among people living with HIV/AIDS attending antiretroviral therapy clinics in Gedeo Zone, Southern Ethiopia.

INTRODUCTION: Opportunistic infections (OIs) are more common and severe among people with suppressed immunity like those living with HIV/AIDS (PLWH). This study aimed to assess the prevalence of OIs and associated factors among PLWH attending antiretroviral therapy (ART) clinics in the Gedeo zone, Southern Ethiopia. METHODS: A facility based retrospective cohort study was conducted from April to June 2018 among PLWH attending ART clinics in Gedeo zone, Ethiopia from November 2016 - November 2017. A simple random sampling method was used to select the both paper based and electronic study participants' charts. Adjusted odds ratios were calculated using multivariable logistic regression analysis for variables statistically significant at 95% confidence interval under bivariable logistic regression analysis, and significance was declared at P < 0.05. RESULTS: a total of 266 PLWH attended the selected ART clinics of Gedeo zone during the one year period were participated in the current study. The majority 104(39.1%) were within the age group 30-39, 106(60.2%) male, 184(69.2%) married, and 167(62.9%) urban residents. The study revealed the prevalence of OIs was 113(42.5%) with oral candidiasis 28(24.5%) the most prevalent followed by pulmonary tuberculosis 22(19.5%) and herpes zoster 15(13.4%). Further, study participants with ambulatory [AOR = 2.40(95% CI: 1.14, 5.03)], and bedridden [AOR = 3.27(95% CI:1.64, 6.52)] working functional status; with lower CD4 count: less than 200cells/mm3 [AOR = 9.14(95% CI: 2.75, 30.39)], 200-350cells/mm3 [AOR = 9.45(95% CI: 2.70,33.06)], 351-500cells/mm3 [AOR = 5.76(95% CI: 1.71, 19.39)]; being poor in ART adherence level [AOR = 10.05(95% CI: 4.31,23.46)]; being in stage III/IV WHO clinical stage of HIV/AIDS [AOR = 2.72(95% CI: 1.42, 5.20)]; and being chewing khat [AOR = 2.84(95% CI: 1.21, 6.65)] were found positively predicting the occurrence of OIs. CONCLUSION: This study speckled a high prevalence of OIs with several predicting factors. Therefore, the study acmes there should be interventional means which tackles the higher prevalence of OIs with focus to the predicting factors like lower CD4 count level, less/bedridden working functional status, poor ART adherence level, advanced stage of HIV/AIDS stage and chewing khat.

The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.

INTRODUCTION: To assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart. METHODS: Medline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R. RESULTS: Of 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59). DISCUSSION: When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies. CONCLUSIONS: The majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression.

Nucleoside/nucleotide reverse transcriptase inhibitor-associated weight gain in people living with HIV: data from the Copenhagen Comorbidity in HIV Infection (COCOMO) study.

Weight gain effects of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in people with HIV (PWH) have been sparsely studied.Participants were enrolled in the Copenhagen Comorbidity in HIV Infection (COCOMO) study. PWH receiving a backbone of emtricitabine, or lamivudine combined with abacavir, tenofovir disoproxil, or tenofovir alafenamide were analysed. Weight gain according to ART backbone and to the third drug was analysed using a multiple linear regression model. Non-ART risk factors were also determined using multiple linear regression.A total of 591 participants were included in the analysis. The majority were middle-aged, virally suppressed males with a mean BMI just above the normal range. Both tenofovir disoproxil/emtricitabine or lamivudine and abacavir /emtricitabine or lamivudine, but not tenofovir alafenamide /emtricitabine or lamivudine were associated with weight gain over two years (0.6 kg, p = 0.025; 1.0 kg, p = 0.005). The third drugs associated with weight increase were non-nucleoside reverse transcriptase inhibitors (NNRTI) (p = 0.035), dolutegravir (p = 0.008) and atazanavir (p = 0.040). Non-ART risk factors for gaining weight were low or normal BMI, age <40 years, underweight, inactivity or highly active at baseline.Tenofovir disoproxil and abacavir-based ART regimens were associated with a small weight gain. Third drug NNRTI, dolutegravir and atazanavir were associated with an increase in weight.

Multilevel determinants of antiretroviral therapy initiation and retention in the test-and-treat era of Nepal: a qualitative study.

BACKGROUND: The transition to the "test-and-treat" policy in Nepal in 2017, coupled with the rapid initiation of antiretroviral therapy (ART) in 2020, necessitates an in-depth understanding of factors influencing ART initiation and retention. This study investigates these factors from the perspectives of healthcare providers, families/communities, and people living with HIV (PLHIV). METHODS: Employing a qualitative design, in-depth interviews were conducted with 24 ART clients and 26 healthcare providers across different provinces of Nepal. A comprehensive interview guide facilitated the exploration of experiences and perceptions. Interviews were transcribed verbatim, and thematic analysis was applied to distill key insights. Guided by a socio-ecological model, interviews were analyzed to identify the barriers and facilitators to ART initiation and continuation at the individual, family/community, and health system levels. RESULTS: Facilitators and barriers were identified at three levels. Individual-level facilitators included fear of death, perceived health benefits, knowledge about HIV/ART, confidentiality, and financial support. Barriers encompassed concerns about lifelong medication, side effects, denial of HIV status, fear of disclosure, and financial constraints. At the family/community level, support from family and community health workers facilitated ART adherence, while social stigma and discrimination posed barriers. The health system's role was dual; the provision of free treatment, a client tracking system and a robust drug supply chain were facilitators, whereas logistical challenges and service accessibility during the COVID-19 pandemic were notable barriers. CONCLUSIONS: This study highlights the various factors that influence ART initiation and retention in Nepal during the test-and-treat era. Tailored interventions should focus on increasing awareness about HIV and ART, strengthening healthcare systems, ensuring availability of medications, and providing accessible treatment during service disruptions. Furthermore, these interventions should encourage supportive environments at the individual, community, and healthcare system levels. Taking this holistic approach is essential for effectively implementing ART and achieving long-term health outcomes in light of changing public health policies.

Noma Masquerading as Squamous Cell Carcinoma - A Case Report in an AIDS Patient.

Rationale: Cancrum oris, also known as noma, is a rare and rapidly progressing gangrenous infection affecting the oral cavity, commonly seen in malnourished children. We discuss the clinical presentation, diagnostic dilemma and management in a 54-year-old male human immunodeficiency virus-positive patient with oral ulceration clinically resembling squamous cell carcinoma (SCC). Patient Concerns: The patient had severe oral ulceration with pain and difficulty eating food. Diagnosis: Histopathological examination was misleading as it revealed features akin to early invasion of SCC. Immunohistochemistry findings were not in favour of SCC. Treatment: Antiretroviral therapy was started owing to the decreased CD4 cell count. Outcomes: Lesions began to show signs of healing on follow-up. Take-away Lessons: This case aims to highlight the unique challenges of diagnosing and emphasises the importance of considering opportunistic infections in immunocompromised patients presenting with oral ulcerations to prevent misdiagnosis and maltreatment.

Suppressed HIV antibody responses following exposure to antiretrovirals - evidence from PrEP randomized trials and early antiretroviral treatment initiation studies.

BACKGROUND: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening. METHODS: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP). RESULTS: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users. Among RV254 participants, reactivity in Ag/Ab assays was <100% at all timepoints, and lower among those initiating ART earlier. Seroreversions occurred for 29% (16/55), and blood donation screening with NAT and Ag/Ab assays could have missed up to 36% (20/55) of RV254 participants. For SIPP participants, who started ART at later timepoints, Ag/Ab assays identified infections with no evidence of reactivity waning. CONCLUSION: PrEP and early ART initiation can delay or reduce HIV detectability. Considerations for the implementation of NAT and Ag/Ab tests in PrEP/PEP programs relying on Ab-only RDTs should be balanced according to feasibility and public health impact. While blood transfusion services using Ab-only RDTs for HIV screening should adopt higher sensitivity tests, surveillance and further research are needed to determine the need for novel HIV testing algorithms for those already using NAT and Ag/Ab screening assays.

Client-reported challenges and opportunities for improved antiretroviral therapy services uptake at a secondary health facility in Ghana.

Antiretroviral therapy (ART) regimens in African countries, including Ghana, are often faced with the challenge of treatment default. To maximize ART utilization and efficiency among people living with HIV (PLHIV), it is pertinent to ensure that ART-related challenges that clients encounter are identified and addressed holistically. A phenomenological qualitative study of thirty participants recruited through the purposive sampling technique was conducted using in-depth interviews from June to July 2021. Independent coding was done using Atlas ti. Sub-themes were developed from the codes, using the most expressive phrases, and grouped under two broad themes, challenges, and opportunities to maximise ART uptake. Ten different challenges, grouped into the health system and individual constraints were reported. Health system constraints included stigmatisation and discrimination by healthcare workers, queuing outside while waiting to be served, long waiting periods, non-communication of laboratory test results to clients, lack of proper education on side effects associated with ART, and language barrier. Individual constraints included financial constraints, perceived non-improvement in health outcomes, food insecurity, and forgetfulness. Opportunities identified for improved ART uptake were assuring ART clients of improved health outcomes, leveraging the good rapport between ART clients and healthcare providers, leveraging the better counselling services offered to PLHIV at the ART clinic, provision of varied ART treatment regimens to clients, routine communication of laboratory test results to clients, and leveraging clients' satisfaction with ART services at ART clinic. We recommend health system reforms targeting healthcare service delivery to PLHIV to encourage linkage, continuity, and retention in care and augmenting ART regimes with financial and nutritional support while encouraging status disclosure to a trusted family member.

Virological impact of HIV drug-resistance testing in children, adolescents, and adults failing first-line ART in Tanzania.

BACKGROUND: Prospective data on the effectiveness of resistance testing in informing treatment decisions and outcomes in with first-line failure in these settings is limited. This study aimed to assess the virological impact of HIV drug-resistance testing in patients with virological failure in Tanzania. METHODS: Participants were randomly assigned to either the control or the experimental group. In addition to the standard of care, patients in the experimental group had access to genotypic drug-resistance testing, information used during treatment change, and were followed up at six-and 12-months to determine virological suppression. RESULTS: A total of 261 patients with a median age of 32 (14.7-44.7) years were enrolled. In the intention-to-treat analysis, at 6-months, suppression was achieved in 58 (42.3%; 95% CI, 34.1-50.1) experimental group patients versus 51 (41.1%; 95% CI, 32.5-49.8) control group patients, with a p-value of 0.4. At-12 months, suppression was achieved in 110 (80.3%; 95% CI, 73.6-87) experimental patients versus 99 (79.8%; 95% CI, 72.8-86.9) control patients, with a p-value of 0.5. In the per-protocol analysis, at 6-months, suppression was observed in 38.46% (95% CI, 27.6-49.3) experimental patients versus 38.6% (95% CI, 26.0-51.2) control patients, with a p-value of 0.5. At 12-months, suppression was observed in 79.49% (95% CI, 70.5-88.5) of experimental patients versus 75.44% (95% CI, 64.3-86.6) of control patients, with a p-value of 0.3. CONCLUSION: Conducting HIV drug-resistance testing, and switch to individualised second-line regimens did not significantly improve virological suppression in patients experiencing first-line ART failure in Tanzania.

Patient and clinic staff perspectives on the implementation of a long-acting injectable antiretroviral therapy program in an urban safety-net health system.

BACKGROUND: Long-acting injectable cabotegravir plus rilpivirine (LAI CAB/RPV) has several potential benefits over daily oral formulations for HIV treatment, including the potential to facilitate long-term adherence and reduce pill fatigue. We aimed to assess facilitators of and barriers to LAI CAB/RPV implementation and delivery through the perspectives of physicians and clinical staff, and the experiences of LAI CAB/RPV use among people living with HIV (PLWH) at a Ryan-White supported safety-net clinic in North Texas. METHODS: We conducted semi-structured interviews with recruited clinic staff (physicians, nurses, and support staff) involved with LAI CAB/RPV implementation and PLWH who switched to LAI CAB/RPV and consented to participate in individual interviews. Data were collected from July to October 2023. Our interview guide was informed by the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM), and Proctor Implementation Outcomes frameworks. Qualitative data were analyzed using a rapid qualitative analysis approach to summarize key themes. RESULTS: We recruited and interviewed 15 PLWH who transitioned to LAI CAB/RPV and 11 clinic staff serving these patients. PLWH conveyed that emotional and informational support from family or a trusted clinician influenced their decision to switch to LAI CAB/RPV. PLWH also reported that injectable treatment was more effective, convenient, and acceptable than oral antiretroviral therapy. Clinic staff and physicians reported that staff training, pharmacist-led medication switches, flexible appointments, refrigeration space and designated room for injection delivery facilitated implementation. Clinic staff cited medication costs, understaffing, insurance prior authorization requirements, and lack of medication access through state drug assistance programs as critical barriers. CONCLUSIONS: Our study offers insights into real-world experiences with LAI usage from the patient perspective and identifies potential strategies to promote LAI CAB/RPV uptake. The barriers to and facilitators of LAI CAB/RPV program implementation reported by clinic staff in our study may be useful for informing strategies to optimize LAI CAB/RPV programs.

Cardiometabolic complications in children and adolescents with HIV on antiretroviral therapy.

INTRODUCTION: The course of HIV infection has changed radically with the introduction of antiretroviral therapy (ART), which has significantly reduced mortality and improved quality of life. However, antiretroviral drugs can cause adverse effects, including cardiometabolic complications and diseases, which are among the most common. Compared to the adult population, there are fewer studies in the pediatric population on treatment-related complications. The purpose of this review is to provide an update on the literature regarding cardiometabolic complications and diseases in children and adolescents with HIV. AREAS COVERED: A comprehensive literature review was conducted using PubMed and related bibliographies to provide an overview of the current knowledge of metabolic complications (dyslipidemia, insulin resistance, lipodystrophy, weight gain and liver complications) and diseases (prediabetes/diabetes and cardiovascular diseases) associated with ART in children and adolescents with HIV. EXPERT OPINION: Metabolic complications are conditions that need to be closely monitored in children and adolescents with HIV, as they increase the risk of early development of non-communicable diseases, such as cardiovascular disease. Key areas for improvement include ensuring access to treatment, reducing side effects and improving diagnostic capabilities. Overcoming existing challenges will require collaborative efforts across disciplines, advances in technology, and targeted interventions to address socioeconomic disparities.

Long-acting injectable antiretroviral treatment: experiences of people with HIV and their healthcare providers in Uganda.

INTRODUCTION: Long-acting injectable antiretroviral treatment (LAI-ART) has emerged as a novel alternative to the burden of daily oral pills. The bi-monthly intramuscular injectable containing cabotegravir and rilpivirine holds the promise of improving adherence to ART. The perspectives of potential users of LAI-ART, the majority of whom reside in Eastern and Southern Africa, are still largely unexplored. We set out to understand the experiences of people with HIV (PWH) who received LAI-ART at Fort Portal Regional Referral Hospital in mid-Western Uganda for at least 12 months. METHODS: This qualitative study, conducted between July and August 2023, was nested within a larger study. We conducted four focus groups with 32 (out of 69) PWH who received intramuscular injections of cabotegravir and rilpivirine. In-depth interviews were held with six health workers who delivered LAI-ART to PWH. Data were analyzed by thematic approach broadly modeled on the five domains of the Consolidated Framework for Implementation Research (CFIR). RESULTS: There was high acceptability of LAI-ART (30 /32 or 94%) participants requested to remain on LAI-ART even after the end of the 12-month trial. Adherence to ART was reportedly improved when compared to daily oral treatment. Participants credited LAI-ART with; superior viral load suppression, redemption from the daily psychological reminder of living with HIV, enhanced privacy in HIV care and treatment, reduced HIV-related stigma associated with taking oral pills and that it absolved them from carrying bulky medication packages. Conversely, nine participants reported pain around the injection site and a transient fever soon after administering the injection as side effects of LAI-ART. Missed appointments for receiving the bi-monthly injection were common. Providers identified health system barriers to the prospective scale-up of LAI-ART which include the perceived high cost of LAI-ART, stringent cold chain requirements, physical space limitations, and workforce skills gaps in LAI-ART delivery as potential drawbacks. CONCLUSION: Overall, PWH strongly preferred LAI-ART and expressed a comparatively higher satisfaction with this treatment alternative. Health system barriers to potential scale-up are essential to consider if a broader population of PWH will benefit from this novel HIV treatment option in Uganda and other resource-limited settings. TRIAL REGISTRATION: Trial Registry Number PACTR ID PACTR202104874490818 (registered on 16/04/2021).

Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility.

Skeletal alterations and their complications can significantly impact the quality of life and overall prognosis of patients living with HIV (PLWHIV). Considering skeletal alterations are often asymptomatic and unapparent during routine clinical evaluation, these conditions are frequently overlooked in the clinical management of PLWHIV. However, since the use of combined antiretroviral therapy (cART) has increased life expectancy in PLWHIV effectively, osteopenia, osteoporosis, and bone fragility are now considered to have a major health impact, with a substantial increase in healthcare costs. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to bone changes in PLWHIV, focusing on the importance of taking a multi-scale approach in the assessment of bone hierarchical organization. Even though a low bone mineral density is frequently reported in PLWHIV, numerous ambiguities still remain to be solved. Recent data suggest that assessment of other bone properties (on various levels of the bone structure) could contribute to our understanding of bone fragility determinants in these individuals. Special attention is needed for women living with HIV/AIDS since a postmenopausal status was described as an important factor that contributes to skeletal alterations in this population. Further research on complex etiopathogenetic mechanisms underlying bone alterations in PLWHIV may lead to the development of new therapeutic approaches specifically designed to reduce the health burden associated with skeletal disorders in this population. A major challenge in the clinical management of PLWHIV lies in the adverse skeletal effects of some frequently prescribed cART regimens (e.g., regimens containing tenofovir disoproxil fumarate), which may require a switch to other pharmacological approaches for maintained HIV infection (e.g., regimens containing tenofovir alafenamide). Taken together, the findings are indicative that the HIV/AIDS status should be taken into consideration when designing new guidelines and strategies for individualized prevention, diagnosis, and treatment of increased bone fragility.

Enhancing Precision in HIV Treatment: Validation of a Robust Next-Generation Sequencing System for Drug Resistance Mutation Analysis.

BACKGROUND: Multidrug-resistant HIV strains challenge treatment efficacy and increase mortality rates. Next-generation sequencing (NGS) technology swiftly detects variants, facilitating personalized antiretroviral therapy. AIM: This study aimed to validate the Vela Diagnostics NGS platform for HIV drug resistance mutation analysis, rigorously assessed with clinical samples and CAP proficiency testing controls previously analyzed by Sanger sequencing. METHOD: The experimental approach involved the following: RNA extraction from clinical specimens, reverse transcription polymerase chain reaction (RT-PCR) utilizing the Sentosa SX 101 platform, library preparation with the Sentosa SQ HIV Genotyping Assay, template preparation, sequencing using the Sentosa SQ301 instrument, and subsequent data analysis employing the Sentosa SQ Suite and SQ Reporter software. Drug resistance profiles were interpreted using the Stanford HIV Drug Resistance Database (HIVdb) with the HXB2 reference sequence. RESULTS: The Vela NGS system successfully identified a comprehensive array of drug resistance mutations across the tested samples: 28 nucleoside reverse transcriptase inhibitors (NRTI), 25 non-nucleoside reverse transcriptase inhibitors (NNRTI), 25 protease inhibitors (PI), and 10 integrase gene-specific variants. Dilution experiments further validated the system's sensitivity, detecting drug resistance mutations even at viral loads lower than the recommended threshold (1000 copies/mL) set by Vela Diagnostics. SCOPE: This study underscores the validation and clinical applicability of the Vela NGS system, and its implementation may offer clinicians enhanced precision in therapeutic decision-making for individuals living with HIV.

Safety of Antiretroviral Exposure During Pregnancy: Opportunities to Close Data Gaps.

Pregnant persons with chronic health conditions often require pharmacotherapy to remain healthy. The Antiretroviral Pregnancy Registry is a prospective, international, voluntary, and exposure registry that collects information on antiretroviral (ARV) exposure; however, a minority of providers use the registry, leaving critical gaps to guide prescribing in this population. The Task Force for the Elimination of Perinatal HIV Transmission in the United States, funded by the Centers for Disease Control and Prevention, has identified the monitoring of ARV safety as a paramount concern in the ongoing mission to eliminate perinatal human immunodeficiency virus (HIV) transmission. As active members of this task force, we urge all healthcare providers who care for pregnant individuals to prioritize reporting all ARV exposures to the registry.