Growing literature has shown heterogenous effects of conditional cash incentives (CCIs) on HIV care retention. The field lacks insights into reasons why incentives impact various patients in different ways–differences that may be due to variations in psychological and social mechanisms of effect. A deeper understanding of patients’ perceptions and experiences of CCIs for retention may help to clarify these mechanisms. We conducted a qualitative study embedded in the ADAPT-R trial (NCT#02338739), a sequential multiple assignment randomized trial (SMART) that evaluated economic incentives to support retention in HIV care among persons living with HIV (PLHIV) initiating antiretroviral therapy in Kenya. Participants who attended their scheduled clinic visits received an incentive of approximately $4 each visit. Interviews were conducted between July 2016 and June 2017 with 39 participants to explore attitudes and experiences with economic incentives conditional on care engagement. Analyses revealed that incentives helped PLHIV prioritize care-seeking by alleviating transport barriers and food insecurity: “I decided to forgo [work] and attend clinic […] the voucher relieved me”. Patients who borrowed money for care-seeking reported feeling relieved from the burden of indebtedness to others: “I borrow with confidence that I will pay after my appointment.” Incentives fostered their autonomy, and enabled them to support others: “I used the money to buy some clothes and Pampers for the children.” Participants who were intrinsically motivated to engage in care (“my life depends on the drugs, not the incentive”), and those who mistrusted researchers, reported being less prompted by the incentive itself. For patients not already prioritizing care-seeking, incentives facilitated care engagement through alleviating transport costs, indebtedness and food insecurity, and also supported social role fulfillment. Conditional cash incentives may be an important cue to action to improve progression through the HIV treatment cascade, and contribute to better care retention.

Gaps in HIV RNA monitoring persist globally impeding the ability to determine clinical progress and outcomes. This study systematically evaluated provider (e.g., guideline non-adherence), system (e.g., laboratory error) and participant-level (e.g., refusal) drivers of missed viral load (VL) monitoring measurements among people with HIV in Kenya. Adults aged 18-65 years were followed across five health facilities in Kenya as part of a clinical trial (NCT#02338739) where HIV RNA monitoring was done routinely. Instances of missed VL despite being indicated per Kenyan guidelines were identified. An algorithm for assessing root causes of missing HIV RNA was developed and generalized linear models estimated the risk ratios (RR) for participant-level characteristics associated with missed viral load. Among 1,754 participants (66% female), the prevalence of missed viral load in year one and two was 24.4% and 29.4%, respectively. Drivers for missed viral load measurements included loss to follow up (51.5% in year one and 57.8% in year two), clinician non-adherence with guidelines (36.7% in year one and 32.2% in year two), unknown (10.3% in year one and 8.6% in year two), and requested but not collected (1.5% in year one and 1.3% in year two). Participants aged < 24 years (RR 2.27, 95% CI: 1.66-3.12), those with higher socioeconomic status (RR 1.47, 95% CI: 1.03-1.91), receiving HIV treatment at a rural clinic (RR 1.22, 95% CI: 1.02-1.46) and with advanced HIV disease (RR 2.39, 95% CI: 1.52-3.73) were more likely to miss VL monitoring. Missed routine viral load monitoring remains high, primarily due to loss to follow-up, and may substantially alter suppression estimates. Sustainable approaches to keep people with HIV engaged in care, alongside strengthening providers' clinical practices and alignment with national guidelines, are necessary for optimizing viral monitoring and accurately assessing viral suppression within public health systems.

The causal dose response curve is commonly selected as the statistical parameter of interest in studies where the goal is to understand the effect of a continuous exposure on an outcome.Most of the available methodology for statistical inference on the dose-response function in the continuous exposure setting requires strong parametric assumptions on the probability distribution. Such parametric assumptions are typically untenable in practice and lead to invalid inference. It is often preferable to instead use nonparametric methods for inference, which only make mild assumptions about the data-generating mechanism. We propose a nonparametric test of the null hypothesis that the dose-response function is equal to a constant function. We argue that when the null hypothesis holds, the dose-response function has zero variance. Thus, one can test the null hypothesis by assessing whether there is sufficient evidence to claim that the variance is positive. We construct a novel estimator for the variance of the dose-response function, for which we can fully characterize the null limiting distribution and thus perform well-calibrated tests of the null hypothesis. We also present an approach for constructing simultaneous confidence bands for the dose-response function by inverting our proposed hypothesis test. We assess the validity of our proposal in a simulation study. In a data example, we study, in a population of patients who have initiated treatment for HIV, how the distance required to travel to an HIV clinic affects retention in care.

Background:Consistent engagement in HIV treatment is needed for healthy outcomes, yet substantial loss-to-follow up persists, leading to increased morbidity, mortality and onward transmission risk. Although conditional cash transfers (CCTs) address structural barriers, recent findings suggest that incentive effects are time-limited, with cessation resulting in HIV care engagement deterioration. We explored incentive experiences, perceptions, and effects after cessation to investigate potential mechanisms of this observation. Methods:This qualitative study was nested within a larger trial, AdaPT-R (NCT02338739), focused on HIV care engagement in western Kenya. A subset of participants were purposively sampled from AdaPT-R participants: adults with HIV who had recently started ART, received CCTs for one year, completed one year of follow-up without missing a clinic visit, and were randomized to either continue or discontinue CCTs for one more year of follow-up. In-depth interviews were conducted by an experienced qualitative researcher using a semi-structed guide within a month of randomization. Interviews were conducted in the participants' preferred language (Dholuo, Kiswahili, English). Data on patient characteristics, randomization dates, and clinic visit dates to determine care lapses were extracted from the AdaPT-R database. A codebook was developed deductively based on the guide and inductively refined based on initial transcripts. Transcripts were coded using Dedoose software, and thematic saturation was identified. Results:Of 38 participants, 15 (39%) continued receiving incentives, while 23 (61%) were discontinued from receiving incentives. Half were female (N = 19), median age was 30 years (range: 19-48), and about three-quarters were married or living with partners. Both groups expressed high intrinsic motivation to engage in care, prioritized clinic attendance regardless of CCTs and felt the incentives expanded their decision-making options. Despite high motivation, some participants reported that cessation of the CCTs affected their ability to access care, especially those with constrained financial situations. Participants also expressed concerns that incentives might foster dependency. Conclusions:This study helps us better understand the durability of financial incentives for HIV care engagement, including when incentives end. Together with the quantitative findings in the parent AdaPT-R study, these results support the idea that careful consideration be exercised when implementing incentives for sustainable engagement effects.

PURPOSE:Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort. METHODS:In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4+ ≥50 cells/μL and HIV plasma RNA <200 copies/mL. Pembrolizumab 200 mg intravenously was administered once every 3 weeks for up to 35 cycles. The primary end point was safety, and the secondary end point was KS response by modified AIDS Clinical Trials Group Criteria. RESULTS:Thirty-two cisgender men enrolled with baseline median CD4+ T-cell count of 274 cells/µL. All but nine participants had received previous systemic KS therapy. Participants received a median of 11 cycles of pembrolizumab (range, 1-35). Sixty-six percent had grade ≥1 treatment-emergent adverse events, including one death from polyclonal KS herpesvirus-related B-cell lymphoproliferation. Thirty-one percent had ≥one immune-mediated AEs (imAEs) with 25% requiring systemic steroids. In 29 participants with evaluable KS, the overall response rate (ORR) was 62.1% (95% CI, 42.3 to 79.3) and did not differ by CD4+ T-cell count. ORR in the eight participants with evaluable disease without previous KS therapy was 87.5% (95% CI, 47.3 to 99.7). Median duration of response (DOR) was not reached, and the Kaplan-Meier estimate of DOR of ≥12 months was 92.3% (95% CI, 56.6 to 98.8). Median progression-free survival was 28.2 months (95% CI, 4.2 to noncalculable). CONCLUSION:Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.

Figure S5 shows physical wellbeing over time

Figure S8 shows social/family well-being over time by response

Background: Adolescents and young adults (AYA) aged 14-24 years living with HIV in Africa experience substantially higher rates of virological failure and HIV-related mortality than adults. We propose to utilize developmentally appropriate interventions with high potential for effectiveness, tailored by AYA pre-implementation, in a sequential multiple assignment randomized trial (SMART) aimed at improving viral suppression for AYA living with HIV in Kenya.Methods: Using a SMART design, we will randomize 880 AYA with HIV in Kisumu, Kenya to either youth-centered education and counseling (standard of care) or electronic peer navigation in which a peer provides support, information, and counseling via phone and automated monthly text messages. Those with a lapse in engagement (defined as either a missed clinic visit by > 14 days or HIV viral load > 1000 copies/ml) will be randomized a second time to one of three higher-intensity re-engagement interventions: (1) standard of care outreach and intensified counseling; (2) conditional cash transfers; and (3) in-person peer navigation. This study will evaluate which interventions and which dynamic sequence of interventions improve sustained viral suppression and HIV care engagement in AYA with HIV at 24 months post-enrollment and assess the cost-effectiveness of successful strategies.Discussion: The study utilizes promising interventions tailored to AYA with HIV while optimizing resources by intensifying services only for those AYA who need more support. Findings from this innovative study will offer evidence for public health programming to end the HIV epidemic as a public health threat for AYA in Africa.

Figure S12 shows functional well-being over time by response

Table S1 shows summary of all adverse events

Figure S2 shows summary of normalized serum levels of cytokins/chemokines/growth factors at week 4

Figure S1 shows tumor marker over time

Figure S9 shows emotional well-being over time

Purpose:Mistletoe extract (ME) is widely used for patients with cancer to support therapy and to improve quality of life (QoL). However, its use is controversial due to suboptimal trials and a lack of data supporting its intravenous administration.Materials and Methods:This phase I trial of intravenous mistletoe (Helixor M) aimed to determine the recommended phase II dosing and to evaluate safety. Patients with solid tumor progressing on at least one line of chemotherapy received escalating doses of Helixor M three times a week. Assessments were also made of tumor marker kinetics and QoL.Results:Twenty-one patients were recruited. The median follow-up duration was 15.3 weeks. The MTD was 600 mg. Treatment-related adverse events (AE) occurred in 13 patients (61.9%), with the most common being fatigue (28.6%), nausea (9.5%), and chills (9.5%). Grade 3+ treatment-related AEs were noted in 3 patients (14.8%). Stable disease was observed in 5 patients who had one to six prior therapies. Reductions in baseline target lesions were observed in 3 patients who had two to six prior therapies. Objective responses were not observed. The disease control rate (percentage of complete/partial response and stable disease) was 23.8%. The median stable disease was 15 weeks. Serum cancer antigen-125 or carcinoembryonic antigen showed a slower rate of increase at higher dose levels. The median QoL by Functional Assessment of Cancer Therapy-General increased from 79.7 at week 1 to 93 at week 4.Conclusions:Intravenous mistletoe demonstrated manageable toxicities with disease control and improved QoL in a heavily pretreated solid tumor population. Future phase II trials are warranted.Significance:Although ME is widely used for cancers, its efficacy and safety are uncertain. This first phase I trial of intravenous mistletoe (Helixor M) aimed to determine phase II dosing and to evaluate safety. We recruited 21 patients with relapsed/refractory metastatic solid tumor. Intravenous mistletoe (600 mg, 3/week) demonstrated manageable toxicities (fatigue, nausea, and chills) with disease control and improved QoL. Future research can examine ME's effect on survival and chemotherapy tolerability.

Table S2 shows treatment-related adverse events by dose level

Table S3 shows reasons for discontinuation with patient charateristics

Figure S7 shows social/family well-being over time

Background Mobile Health (“mHealth”) interventions have shown promise in improving HIV treatment outcomes for stigmatized populations. This paper presents the findings from a randomized controlled trial to assess the efficacy, participant-level feasibility and acceptability of a theory-informed mHealth intervention, Motivation Matters! , designed to improve viral suppression and ART adherence among HIV-seropositive women who engage in sex work in Mombasa, Kenya. Methods A total of 119 women were randomized between the intervention and standard of care control. The primary outcome examined viral suppression ( ≤ 30 copies/mL) six months following ART initiation. ART adherence was assessed monthly using a visual analogue scale. Participant-level feasibility was measured through response rates to study text messages. Acceptability was assessed through qualitative exit interviews. Results Six months following treatment initiation, 69% of intervention and 63% of control participants were virally suppressed (Risk Ratio [RR] = 1.09, 95% Confidence Interval [95% CI] (0.83, 1.44). Among women who were viremic at baseline and endorsed engagement in sex work, 74% of women in the intervention arm compared with 46% of women in the control arm achieved viral suppression at month six RR = 1.61, 95% CI (1.02, 2.55). Adherence was higher in intervention versus control participants every month. All participants responded to at least one message, and there was a 55% overall response rate to intervention text messages. Qualitative exit interviews suggested high acceptability and perceived impact of the intervention. Conclusion The improvements in ART adherence and viral suppression, combined with encouraging data on feasibility and acceptability, provides preliminary evidence that Motivation Matters! could support ART adherence and viral suppression in women who engage in sex work. Trial registration This trial was registered with ClinicalTrials.gov (NCT02627365, 10/12/2015; http://clinicaltrials.gov ).

Figure S3 shows functional assessment of cancer therapy - general over time

Figure S4 shows functional assessment of cancer therapy - general over time by response