HIV Virologic Suppression Research Articles

P-573. Analysis of Cabotegravir-Rilpivirine Use in HIV Patients at MedStar Washington Hospital Center

Abstract Background Intramuscular cabotegravir-rilpivirine (CAB-RPV) is a long-acting antiretroviral for the treatment of HIV which can be administered every 1-2 months. Registration trials demonstrated the non-inferiority of CAB-RPV versus oral antiretroviral therapy, but data on the ‘real world’ performance of CAB-RPV is sparse. In addition, these trials required HIV virologic suppression (viral load (VL) < 50 copies/mL) with oral medications before transitioning to CAB-RPV. Small studies have reported success when CAB-RPV was started in patients with detectable viremia, and our study sought to build on those findings. Methods Descriptive, retrospective study based on patients who began treatment with CAB-RPV between May 2022-Nov 2023. Virologic undetectability (VL < 50 copies/mL), suppression (VL 51-200 copies/mL) and virologic failure (VL > 201 copies/mL) at last measurement are described among patients with a VL < 50 copies/mL, 51-200 copies/mL or >201 copies/mL at baseline. Results 42 patients are included in the analysis with a median age of 42 (range 27-80). The cohort was 93% African American, 60% male and 81% received Medicare/Medicaid or both as their primary insurer. Median CD4 count was 861 (range 15-1827) and median viral load was 40 copies/mL (range < 20-294,000). Among 38 patients with a baseline VL of < 50, 34 maintained viral undetectability, 1 become virally suppressed (VL=60) and 3 did not have results available due to recently starting CAB-RPV. One patient with baseline viral suppression (VL=90) became virally undetectable. Two patients with baseline virologic failure (VL 1,210 and 7,200) became virologically undetectable. One patient with baseline virological failure (VL=294,000) developed resistance shortly after starting therapy. Conclusion Similar to data in registration trials, CAB-RPV maintained viral suppression in 100% of patients who were at least virally suppressed at baseline. Two patients with virological failure at baseline achieved virological suppression, adding to data that CAB-RPV may be beneficial in patients who are unable to adhere to oral antivirals. One patient with baseline virological failure and high viral load quickly developed resistance after starting therapy, supporting data that CAB-RPV needs to be used carefully in certain populations. Disclosures All Authors: No reported disclosures

Booster-free anti-retroviral therapy for persons living with HIV and multidrug resistance (B-Free): protocol for a multicentre, multistage, randomised, controlled, non-inferiority trial

IntroductionAnti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk...

Risk of tuberculosis after achieving HIV virological suppression on antiretroviral therapy: a Danish nationwide prospective cohort study.

In countries with low tuberculosis (TB) burden, the risk of TB in people with HIV (PWH) once HIV virological suppression is achieved is not fully understood. In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior TB disease. We used Kaplan-Meier estimation and Poisson regression to calculate TB incidence rate (IR) after six months of ART, along with associated risk factors and mortality rates (MR). Among 6,849 PWH initiating ART (median follow-up 7.4 years), 84 developed TB (IR 1.4/1000 person-year [PY]), 54 of them beyond six months of ART initiation, IR 0.97/1000 PY (95%CI:1.17-1.79): 1.95 (95%CI:1.34-2.76) in non-Danish born, 0.36 (95%CI:0.21-0.62) in Danish-born without injection drug use (IDU), and 2.95 (95%CI:1.53-5.66) in Danish-born with IDU. Danish-born with suppressed viremia, and no IDU or known TB exposures had the lowest risk (IR 0.05/1000 PY).In the adjusted analysis, being non-Danish born (aIRR 4.27[95%CI:2.36-7.72]), IDU (aIRR 4.95[95%CI:2.55-9.62]), and previous AIDS-defining events (aIRR 2.05[95%CI:1.06-3.94]) raised TB risk, while suppressed HIV-RNA (aIRR 0.58[95%CI:0.34-0.99]) reduced it. The overall MR for HIV/TB co-infected post- ART was high, at 48.9/1000 PY (95%CI:30.4-78.7). The TB risk remains elevated in PWH beyond six months of ART initiation, especially among migrants, IDU, those without suppressed HIV-RNA, and individuals exposed to high TB endemic areas or with social risk determinants of health. Conversely, PWH without these risk factors have a TB risk similar to the general population and would not require targeted TB screening strategies.

Correction to: Multilevel Resilience and HIV Virologic Suppression Among African American/Black Adults in the Southeastern United States

Correction to: Multilevel Resilience and HIV Virologic Suppression Among African American/Black Adults in the Southeastern United States

Trajectories of CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio in patients with HIV and long-term virological suppression based on Yunnan HIV cohort.

Our objective was to evaluate the trajectory of immunology in patients with HIV with different baseline CD4 T-cell count strata after antiretroviral therapy (ART) under long-term viral suppression. This was a sub-analysis focused on patients with virological suppression for at least 5 years after ART. Data were obtained from the Yunnan HIV cohort in China. Patients were categorized according to prespecified baseline CD4 T-cell counts. The trajectories of CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio changing over time were fitted using a B-spline regression model. The Cox proportional hazards regression model was used to assess the association of baseline CD4 T-cell count with the risk of both immunological responder (IR) and CD4/CD8 ratio normalization. A total of 2618 patients with a median follow-up of 7.25 years (interquartile range [IQR] 5.92-8.75) were included. Over a period of 12 years, the mean CD4 T-cell count remained above 500 cells/μL in all groups. The mean CD4/CD8 ratio was solely normalized in patients whose baseline CD4 T-cell counts were above 350 cells/μL. Patients with higher baseline CD4 T-cell counts showed higher risks of both IR and CD4/CD8 ratio normalization than those with the lowest (all p trend <0.001). A higher baseline CD4 T-cell count predicted a shorter time for both IR and CD4/CD8 ratio normalization. Long-term, sustained viral suppression may not be able to fully normalize immunological functions in patients with HIV. A high baseline CD4 T-cell count benefits IR and CD4/CD8 ratio normalization.

Clinical Outcomes in Children With Human Immunodeficiency Virus Treated for Nonsevere Tuberculosis in the SHINE Trial.

Children with human immunodeficiency virus (HIV, CWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated outcomes in CWH and children not living with HIV treated for nonsevere TB in the SHINE trial. SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CWH. Of 1204 children enrolled, 127 (11%) were CWH, of similar age (median, 3.6 years; interquartile range, 1.2, 10.3 versus 3.5 years; 1.5, 6.9; P = .07) but more underweight (weight-for-age z score, -2.3; (3.3, -0.8 versus -1.0; -1.8, -0.2; P < .01) and anemic (hemoglobin, 9.5 g/dL; 8.7, 10.9 versus 11.5 g/dL; 10.4, 12.3; P < .01) compared with children without HIV. A total of 68 (54%) CWH were ART-naive; baseline median CD4 count was 719 cells/mm3 (241-1134), and CD4% was 16% (10-26). CWH were more likely to be hospitalized (adjusted odds ratio, 2.4; 1.3-4.6) and to die (adjusted hazard ratio [aHR], 2.6; 95% confidence interval [CI], 1.2 to 5.8). HIV status, age <3 years (aHR, 6.3; 1.5, 27.3), malnutrition (aHR, 6.2; 2.4, 15.9), and hemoglobin <7 g/dL (aHR, 3.8; 1.3,11.5) independently predicted mortality. Among children with available viral load (VL), 45% and 61% CWH had VL <1000 copies/mL at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 versus 6 months) on TB treatment outcomes by HIV status (P for interaction = 0.42). We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CWH treated for nonsevere TB. Irrespective of TB treatment duration, CWH had higher rates of mortality and hospitalization than their counterparts without HIV. Clinical Trials Registration. ISRCTN63579542.

Association between smoking and lack of HIV virological suppression in a cross-sectional study of persons with HIV on antiretroviral therapy in Uganda.

Smoking and alcohol use frequently co-occur and are the leading causes of preventable death in sub-Saharan Africa (SSA) and are common among people living with HIV (PLWH). While alcohol use has been shown to be associated with reduced adherence to antiretroviral treatment (ART), which may affect HIV viral suppression, the independent effect of smoking on HIV outcomes in SSA is unknown. We aimed to 1) describe the prevalence of current smoking and correlates of smoking; 2) assess the association of smoking with viral suppression, adjusting for level of alcohol use; 3) explore the relationship between smoking and CD4 cell count <350 cells/mm3, among participants who are virally suppressed. We analyzed data from the Drinkers Intervention to Prevent Tuberculosis (DIPT) and the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) studies conducted in Southwest Uganda. The studies enrolled PLWH who were on ART for at least 6 months and co-infected with latent tuberculosis and dominated with participants who had unhealthy alcohol use. Current smoking (prior 3 months) was assessed by self-report. Alcohol use was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C, modified for prior 3 months) and phosphatidylethanol (PEth), an alcohol biomarker. We used logistic regression to estimate the cross-sectional association between smoking and lack of virological suppression (≥40 copies/ml), adjusting for level of alcohol use and other covariates, and to examine the association between smoking and CD4 cell counts among PLWH with viral suppression. Of the 955 participants enrolled from 2017 to 2021 who had viral load (VL) results, 63% were men, median age was 40 years (interquartile range [IQR] 32-47), 63% engaged in high/very high-risk alcohol use (AUDIT-C≥6 or PEth≥200 ng/mL), and 22% reported smoking in the prior 3 months. Among 865 participants (91%) with viral suppression and available CD4 count, 11% had a CD4 cell count <350 cells/mm3. In unadjusted and adjusted analyses, there was no evidence of an association between smoking and lack of virological suppression nor between smoking and CD4 count among those with viral suppression. The prevalence of smoking was high among a study sample of PLWH in HIV care with latent TB in Southwest Uganda in which the majority of persons engaged in alcohol use. Although there was no evidence of an association between smoking and lack of virological suppression, the co-occurrence of smoking among PLWH who use alcohol underscores the need for targeted and integrated approaches to reduce their co-existence and improve health.

National impact of SARS-CoV-2 infection on HIV virological suppression in South Africa.

Coronavirus disease (COVID-19) severely disrupted routine healthcare globally. This study assessed the impact of successive COVID-19 waves on HIV viral load (VL) suppression in South Africa, using the national public sector laboratory database. Guidelines recommend VL monitoring at 6 months after treatment initiation, and annually once suppressed, or more frequently if unsuppressed. Specimen-level VL data was extracted for the period January 2019 to December 2021. We assessed the national percentage of samples with a VL <50 (virological suppression), 50-999 (low-level viremia) and ≥1000 (viraemia) copies/mL. Data was analysed by calendar year and month. Data for 2019 (pre-COVID-19) was compared to the 2020 and 2021 calendar years (lockdowns imposed). The national number of COVID-19 cases was reported to indicate the wave periods as follows: one (ancestral)-June to August 2020; two (Beta)-December 2020 to January 2021; three (Delta)-June to August 2021 and four (Omicron)-December 2021. Data is reported for 17,460,264 samples, with 5,608,733, 5,840,056 and 6,011,475 tests performed in 2019, 2020 and 2021 respectively. Overall, a VL of <50, 50-999 and ≥1000 copies/mL were reported for 69.4%, 17.3% and 13.4% of samples. A VL <50 copies/mL was reported for 67.7%, 70.3% and 70.0% of patients in 2019, 2020 and 2021 respectively. For the 2020 and 2021 calendar years, the monthly percentage of patients with a VL <50 copies/mL ranged between 64.6% to 72.7%. Our findings indicate that Covid-19 has not had a substantial impact on the percentage of samples with virological suppression at the national level.

IVY: protocol for a randomised clinical trial to test the effect of a technology-based intervention to improve virological suppression among young adults with HIV in the USA

IntroductionYoung adults with HIV (YWH) experience worse clinical outcomes than adults and have high rates of substance use (SU) and mental illness that impact their engagement in care and adherence...

Integrated Care Models: HIV and Substance Use.

Behaviors and practices associated with substance use contribute to lack of HIV virologic suppression and onward transmission. In the USA, many recent HIV outbreaks have been connected with substance use. Evidence-based strategies for integrating care of those at risk for and living with HIV and who use substances continue to evolve. This review, based on scientific and medical literature through March 2023, provides an overview and evaluation of initiatives for integrated care aimed to serve patients at risk for and with HIV and a substance use disorder. Integrated care services can improve health outcomes for patients at risk for and with HIV and a substance use disorder; for instance, treatment for an opioid use disorder can help improve HIV viral suppression. Brick-and-mortar facilities can provide successful care integration with appropriate clinic leadership to support multidisciplinary care teams, up-to-date provider training, and sufficient pharmacy stock for substance use treatment. Delivering healthcare services to communities (e.g., mobile healthcare clinics and pharmacies, telehealth) may prove to be an effective way to provide integrated services for those with or at risk of HIV and substance use disorders. Incorporating technology (e.g., mobile phone applications) may facilitate integrated care. Other venues, including harm reduction programs and carceral settings, should be targets for integrated services. Venues providing healthcare should invest in integrated care and support legislation that increases access to services related to HIV and substance use.

Telemedicine and HIV Care Quality Measures During the COVID-19 Pandemic.

During the COVID-19 pandemic, telemedicine was adopted to ensure continuity of HIV care. We examined how introducing televisits affected technical quality of care for people with HIV (PWH) during this time. PWH receiving HIV care at Howard Brown Health Centers and Northwestern University in Chicago, Illinois were included. HIV care quality indicators were calculated using data extracted from electronic medical records during 4 timepoints every 6 months from March, March 1, 2020 to September 1, 2021. Generalized linear mixed models estimated differences in indicators across timepoints within each site while controlling for multiple observations of individuals. Generalized linear mixed models were also used to compare differences in outcomes among PWH who attended all versus a combination of in-person and televisits versus no televisits across the study time periods. 6447 PWH were included in the analysis. Compared with prepandemic levels, there were significant declines in care utilization and processes of care measures. Measures of HIV virologic suppression, blood pressure control, and HbA1C <7% (in both people with and without diabetes) were stable with no significant differences noted across the study timepoints. Similar trends were observed across all age, race, and sex subgroups. In multivariable models, televisits were not associated with decreased HIV viral suppression. During the COVID-19 pandemic and rapid implementation of televisits, indicators of care utilization and processes of care decreased compared with prepandemic levels. Among PWH who remained in care, televisits were not associated with worse virologic, blood pressure, and glycemic control in PWH.

Patient perspectives of antiretroviral pharmacy services: A cross-sectional cohort study.

Adherence to antiretroviral therapy (ART) remains the main predictor of sustained HIV virologic suppression for people with HIV (PWH). Mail-order pharmacy services are often offered to patients as an alternative option to traditional pharmacy services. Some payers mandate ART to be dispensed from specific mail-order pharmacies regardless of patient choice complicating ART adherence for patients affected by social disparities. Yet, little is known about patient perspectives regarding mail-order mandates. Eligible patients of the HIV program at University of Nebraska Medical Center with experience receiving ART from both a local and mail-order pharmacy were invited to complete a 20-question survey with three core sections: experiences/perspectives on local and mail-order pharmacy settings; pharmacy attributes rankings; and pharmacy preference. Paired t-tests and Mann-Whitney tests were used to compare the agreement scores of pharmacy attributes. Sixty patients (N = 146; 41.1%) responded to the survey. Mean age was 52 years. Most were male (93%) and White (83%). The majority of participants were on ART for HIV treatment (90%) and 60% were using mail-order pharmacies for their prescription services. Significant scoring differences (p<0.05) were observed for all pharmacy attributes favoring local pharmacies. Refilling ease was the most important attribute noted. More respondents (68%) preferred local pharmacies versus mail-order pharmacies. Payer associated mail-order pharmacy mandates were experienced by 78% with half believing the mandates impacted their medical care negatively. In this cohort study, respondents preferred local pharmacies compared to mail-order pharmacy for ART prescription services and noted ease of refilling as the most important pharmacy attribute. Two-thirds of respondents believed mail-order pharmacy mandates negatively affected their health. Insurance payers should consider the removal of mail-order pharmacy mandates to allow patient choice of pharmacy, which may help remove barriers to ART adherence and improve long-term health outcomes.

Multilevel Resilience and HIV Virologic Suppression Among African American/Black Adults in the Southeastern United States.

To assess overall and byneighborhood risk environments whether multilevel resilience resources were associated with HIV virologic suppression among African American/Black adults in the Southeastern United States. This clinical cohort sub-study included 436 African American/Black participants enrolled in two parent HIV clinical cohorts. Resilience was assessed using the Multilevel Resilience Resource Measure (MRM) for African American/Black adults living with HIV, where endorsement of a MRM statement indicated agreement that a resilience resource helped a participant continue HIV care despite challenges or was present in a participant's neighborhood. Modified Poisson regression models estimated adjusted prevalence ratios (aPRs) for virologic suppression as a function of categorical MRM scores, controlling for demographic, clinical, and behavioral characteristics at or prior to sub-study enrollment. We assessed for effect measure modification (EMM) by neighborhood risk environments. Compared to participants with lesser endorsement of multilevel resilience resources, aPRs for virologic suppression among those with greater or moderate endorsement were 1.03 (95% confidence interval: 0.96-1.11) and 1.03 (0.96-1.11), respectively. Regarding multilevel resilience resource endorsement, there was no strong evidence for EMM by levels of neighborhood risk environments. Modest positive associations between higher multilevel resilience resource endorsement and virologic suppression were at times most compatible with the data. However, null findings were also compatible. There was no strong evidence for EMM concerning multilevel resilience resource endorsement, which could have been due to random error. Prospective studies assessing EMM by levels of the neighborhood risk environment with larger sample sizes are needed.

Leveraging mHealth and Patient Supporters for African Americans' and Latinxs' Engagement in HIV Care (LEAN): Protocol for a Randomized, Controlled, Effectiveness-Implementation Trial

Despite substantial investments in ending the HIV epidemic, disparities in HIV care persist, and there is an urgent need to evaluate novel and scalable approaches to improving HIV care engagement and viral suppression in real-world settings. This paper aims to describe a study protocol for a pragmatic type II hybrid effectiveness-implementation randomized controlled trial comparing existing standard of care clinic HIV linkage, adherence, and retention (LAR) protocols to a mobile health (mHealth)-enhanced linkage, adherence, and retention (mLAR) intervention. The study will enroll 450 participants from clinics in Baltimore City. Eligibility criteria include being ≥18 years of age, having a new HIV diagnosis or being HIV-positive and out of care, or being HIV-positive and deemed by clinic staff as someone who could benefit from linkage and retention services. Participants randomized to the intervention receive mHealth-supported patient navigation for 12 months. Participants in the control group receive the referring clinic's standard of care patient support. The primary outcome is HIV virologic suppression at 12 months. A subset of participants will be interviewed at 12 months to learn about their HIV care experiences and, for those in the intervention arm, their experiences with the mLAR intervention. This protocol was developed in collaboration with the Baltimore City Health Department (BCHD) and the Maryland Department of Health (MDH) and with input from a community advisory board. Enrollment began on February 25, 2020. As of August 11, 2022, 411 of the 450 target participants had been enrolled. Pragmatic implementation science trials designed with input from key stakeholders, including health departments and community members, can help evaluate the evidence for mHealth interventions to reduce HIV health disparities. ClinicalTrials.gov NCT03934437; https://clinicaltrials.gov/ct2/show/NCT03934437. DERR1-10.2196/42691.

1103. Virologic and Immunologic Outcomes in People Living with HIV in a Correctional Setting During the SARS-CoV-2 Pandemic

Abstract Background It is known that the pandemic increased the risk of severe illness from SARS-CoV-2 infection in immunocompromised patients as compared to the general public. To combat this issue, telemedicine was utilized in various settings, but there is very little data on the adequate continuity of care (COC) and sustainability of telehealth throughout the pandemic. There is even less data on the effects of the pandemic in special populations, such as people living with human immunodeficiency virus (PLWH) and within the correctional setting. The purpose of this study was to investigate rates of HIV virologic suppression (VS) and the sustainability of telemedicine throughout the SARS-CoV-2 pandemic. Methods This was a retrospective, pre-post cohort study of PLWH who received antiretroviral therapy (ART) within Illinois Department of Corrections (IDOC) / University of Illinois Chicago telemedicine clinic between 3/2019 and 3/2021. Patients who were released from IDOC or reincarcerated during the study period were excluded. The primary endpoint compared the rate of HIV VS pre-, peri- and post-SARS-CoV-2 restrictions. Secondary endpoints included change in immunologic function pre-, peri- and post-SARS-CoV-2 restrictions, incidence of SARS-CoV-2 infection, number of hospitalizations, development of virologic failure, and change in ART post-pandemic. Other factors known to influence COC were also collected. Results Of 320 patients screened, 225 were included. The majority were Black males (73.7%) and 95.1% had a CD4 T-cell count &amp;gt; 200 cells/mm3 at baseline. Approximately 88% of patients were on a single tablet regimen, with most receiving bictegravir/emtricitabine/tenofovir alafenamide. Rates of HIV VS are summarized in Figure 1 and secondary outcomes are summarized in table 1. Factors associated with disruption of COC included non-adherence to appointments (62.6%) and ART (4.4%). Figure 1Rates of HIV viral suppression (&amp;lt;200 copies/mL), n(%) Table 1 Secondary outcomes Conclusion Results demonstrated that PLWH within IDOC had sustained VS and COC throughout the SARS-CoV-2 pandemic with telemedicine. These results describe how the pandemic impacted PLWH in a correctional setting and future studies could contribute to creating national guidance for telemedicine models to streamline clinical practice. Disclosures All Authors: No reported disclosures.

Response of Care Services for Patients with HIV/AIDS during a Pandemic: Perspectives of Health Staff in Bolivia.

The COVID-19 pandemic has caused an unprecedented crisis striking health services, generating risks of setbacks in health care and affecting the most vulnerable populations such as HIV patients. This study aims to explore the impact of the COVID-19 pandemic on the operational management of health services for people living with HIV/AIDS in Cochabamba, Bolivia. We applied a qualitative approach using semi-structured in-depth interviews with ten key health professionals who care for patients with HIV/AIDS in Cochabamba, Bolivia. Interviews were transcribed verbatim and uploaded to Atlas.ti software for analysis. We used an ethnographic approach within the interpretive paradigm to carry out the thematic analysis, considering the “Determinants of health systems resilience framework” of five dimensions developed by the World Health Organization. Even though the provision of services in public care services was not interrupted during the COVID-19 pandemic, health service delivery was severely affected. Digital technology could be used to compensate in urban areas. Regarding the distribution of medications, adaptative strategies to reduce patient complications were implemented. Unfortunately, the complementary tests availability was limited. The COVID-19 pandemic had a significant impact on HIV/AIDS patient care services in Cochabamba, with repercussions for HIV treatment access and virologic suppression.

HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population.

Dolutegravir and doravirine are individually safe and effective antiretroviral therapy (ART) components, but their combined use has not been studied in clinical trials and is not recommended in HIV treatment guidelines. We noted persons with HIV (PWH) receiving dolutegravir with doravirine at our Washington, DC, infectious disease clinic and undertook a service evaluation to understand why providers selected this ART, whether HIV virologic suppression was achieved and identify adverse effects of concomitant use. Case registry and prescriptions data identified 21 PWH receiving concomitant dolutegravir and doravirine with mean follow-up 576.1days (range 413-751); frequent reasons for switching were multiple ART resistance (57.1%), proton pump inhibitor usage (28.6%) and renal failure (28.6%), with 52.4% switched from protease inhibitor or cobicistat-boosted regimens. Dolutegravir with doravirine alone was prescribed for 60%, and additional ART in 40%. During 12 months follow-up mean CD4 was 585.9 (baseline 570.7) with undetectable viral load in 77.8% (baseline 66.7%). No discontinuations for drug-related adverse events or virologic failure occurred. Dolutegravir with doravirine was well tolerated in small numbers of highly treatment experienced PWH at our clinic, achieving virologic suppression in most. Establishing the efficacy and safety of dolutegravir with doravirine for HIV treatment in randomized trials remains important.

Providing “a beam of light to see the gaps”: determinants of implementation of the Systems Analysis and Improvement Approach applied to the pediatric and adolescent HIV cascade in Kenya

BackgroundChildren and adolescents living with HIV have poorer rates of HIV testing, treatment, and virologic suppression than adults. Strategies that use a systems approach to optimize these multiple, linked steps simultaneously are critical to close these gaps.MethodsThe Systems Analysis and Improvement Approach (SAIA) was adapted and piloted for the pediatric and adolescent HIV care and treatment cascade (SAIA-PEDS) at 6 facilities in Kenya. SAIA-PEDS includes three tools: continuous quality improvement (CQI), flow mapping, and pediatric cascade analysis (PedCAT). A predominately qualitative evaluation utilizing focus group discussions (N = 6) and in-depth interviews (N = 19) was conducted with healthcare workers after implementation to identify determinants of implementation. Data collection and analysis were grounded in the Consolidated Framework for Implementation Research (CFIR).ResultsOverall, the adapted SAIA-PEDS strategy was acceptable, and the three tools complemented one another and provided a relative advantage over existing processes. The flow mapping and CQI tools were compatible with existing workflows and resonated with team priorities and goals while providing a structure for group problem solving that transcended a single department’s focus. The PedCAT was overly complex, making it difficult to use. Leadership and hierarchy were complex determinants. All teams reported supportive leadership, with some describing in detail how their leadership was engaged and enthusiastic about the SAIA-PEDS process, by providing recognition, time, and resources. Hierarchy was similarly complex: in some facilities, leadership stifled rapid innovation by insisting on approving each change, while at other facilities, leadership had strong and supportive oversight of processes, checking on the progress frequently and empowering teams to test innovative ideas.ConclusionCQI and flow mapping were core components of SAIA-PEDS, with high acceptability and consistent use, but the PedCAT was too complex. Leadership and hierarchy had a nuanced role in implementation. Future SAIA-PEDS testing should address PedCAT complexity and further explore the modifiability of leadership engagement to maximize implementation.

A small cluster randomised clinical trial to improve health outcomes among Argentine patients disengaged from HIV care

SummaryBackgroundPatients disengaged from HIV care, e.g., missed medication pick-ups, not attending physician visits, account for ≥70% of new HIV infections. Re-engaging and sustaining engagement is essential to controlling the HIV pandemic. This study tested a physician-delivered evidence-based intervention, Motivational Interviewing (MI), to improve health outcomes, adherence to antiretroviral therapy (ART), HIV virologic suppression, CD4+ count, retention in HIV care, and self-efficacy among patients disengaged from care in Argentina.MethodsRegional clinics (n = 6) were randomised to condition, MI Intervention or Enhanced Standard of Care (ESOC), and recruited N = 360 patients disengaged from HIV care. ART adherence, HIV RNA viral load, CD4+ count retention, and self-efficacy were assessed at baseline, 6, 12, 18, and 24-months. Indirect effects from condition to main outcomes were examined using patient–provider relationship as a mediator. The study was a cluster-randomised clinical trial entitled Conexiones y Opciones Positivas en la Argentina 2 (COPA2) and was registered at clinicaltrials.gov, NCT02846350.FindingsParticipants were an average age of 39·15 (SD = 10·96), 51% were women; intervention participants were older (p = ·019), and more ESOC participants were women (60% vs. 42%, p = 0·001). Using mixed models, the intervention had no effect on ART adherence over time by condition on HIV RNA viral load, CD4+ count retention, or self-efficacy. However, analysing mediated paths, there was an indirect effect of condition on ART adherence (B = 0·188, p = 0·009), HIV viral load (B = −0·095, P = 0·027), and self-efficacy (B = 0·063, P = 0·001), suggesting the intervention was associated with improved patient–provider relationships, which was in turn associated with increased ART adherence, lower HIV viral load, and higher self-efficacy.InterpretationThese findings suggest that physician-delivered MI may enhance the patient-provider relationship, self-efficacy, and ART adherence, and reduced HIV viral load in patients disengaged from HIV care. However, these findings are preliminary due to the small number of clusters randomised, and replication is warranted.FundingNational Institutes of Health.

Two or more significant life-events in 6-months are associated with lower rates of HIV treatment and virologic suppression among youth with HIV in Uganda and Kenya

ABSTRACT Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15–24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (<400 copies/ul). Recent significant life-events were prevalent (57.7%). Having >2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa. Trial registration: ClinicalTrials.gov identifier: NCT03848728..