Novel community health worker strategy for HIV service engagement in a hyperendemic community in Rakai,Uganda: A pragmatic,cluster-randomized trial

BackgroundEffective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called “Health Scouts” to promote engagement in HIV treatment and prevention services.Methods and findingsThe study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV–positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV–positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect.ConclusionsA novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02556957","term_id":"NCT02556957"}}NCT02556957.

Larry Chang and co-workers study an intervention by which community health workers aim to promote engagement in HIV treatment and prevention services in Uganda.     

SMS messaging to improve retention and viral suppression in prevention of mother-to-child HIV transmission (PMTCT) programs in Kenya: A 3-arm randomized clinical trial

BackgroundPregnant and postpartum women living with HIV (WLWH) need support for HIV and maternal child health (MCH) care, which could be provided using short message service (SMS).Methods and findingsWe compared 2-way (interactive) and 1-way SMS messaging to no SMS in a 3-arm randomized trial in 6 MCH clinics in Kenya. Messages were developed using the Health Belief Model and Social Cognitive Theory; HIV messages were integrated into an existing MCH SMS platform. Intervention participants received visit reminders and prespecified weekly SMS on antiretroviral therapy (ART) adherence and MCH, tailored to their characteristics and timing. Two-way participants could message nurses as needed. Clinic attendance, viral load (VL), and infant HIV results were abstracted from program records. Primary outcomes were viral nonsuppression (VL ≥1,000 c/ml), on-time clinic attendance, loss to follow-up from clinical care, and infant HIV-free survival. Among 824 pregnant women randomized between November 2015 and May 2017, median age was 27 years, gestational age was 24.3 weeks, and time since initiation of ART was 1.0 year. During follow-up to 2 years postpartum, 9.8% of 3,150 VL assessments and 19.6% of women were ever nonsuppressed, with no significant difference in 1-way versus control (11.2% versus 9.6%, adjusted risk ratio (aRR) 1.02 [95% confidence interval (CI) 0.67 to 1.54], p = 0.94) or 2-way versus control (8.5% versus 9.6%, aRR 0.80 [95% CI 0.52 to 1.23], p = 0.31). Median ART adherence and incident ART resistance did not significantly differ by arm. Overall, 88.9% (95% CI 76.5 to 95.7) of visits were on time, with no significant differences between arms (88.2% in control versus 88.6% in 1-way and 88.8% in 2-way). Incidence of infant HIV or death was 3.01/100 person-years (py), with no significant difference between arms; risk of infant HIV infection was 0.94%. Time to postpartum contraception was significantly shorter in the 2-way arm than control. Study limitations include limited ability to detect improvement due to high viral suppression and visit attendance and imperfect synchronization of SMS reminders to clinic visits.ConclusionsIntegrated HIV/MCH messaging did not improve HIV outcomes but was associated with improved initiation of postpartum contraception. In programs where most women are virally suppressed, targeted SMS informed by VL data may improve effectiveness. Rigorous evaluation remains important to optimize mobile health (mHealth) interventions.Trial registrationClinicalTrials.gov number {"type":"clinical-trial","attrs":{"text":"NCT02400671","term_id":"NCT02400671"}}NCT02400671.

John Kinuthia and co-workers study one- and two-way text messaging for impact on HIV and maternal health outcomes in women with HIV infection.     

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis

BackgroundSuboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD).Methods and findingsIn this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon.ConclusionsDCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment.Trial registrationclinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03519425","term_id":"NCT03519425"}}NCT03519425.

In a randomised trial, Peter MacPherson and colleagues investigate the costs, timeliness, and completeness of computer-aided X-ray screening for tuberculosis and HIV testing in adults with cough in Malawi.     

Financial incentives and deposit contracts to promote HIV retesting in Uganda: A randomized trial

BackgroundFrequent retesting for HIV among persons at increased risk of HIV infection is critical to early HIV diagnosis of persons and delivery of combination HIV prevention services. There are few evidence-based interventions for promoting frequent retesting for HIV. We sought to determine the effectiveness of financial incentives and deposit contracts in promoting quarterly HIV retesting among adults at increased risk of HIV.Methods and findingsIn peri-urban Ugandan communities from October to December 2018, we randomized HIV–negative adults with self-reported risk to 1 of 3 strategies to promote HIV retesting: (1) no incentive; (2) cash incentives (US$7) for retesting at 3 and 6 months (total US$14); or (3) deposit contracts: participants could voluntarily deposit US$6 at baseline and at 3 months that would be returned with interest (total US$7) upon retesting at 3 and 6 months (total US$14) or lost if participants failed to retest. The primary outcome was retesting for HIV at both 3 and 6 months. Of 1,482 persons screened for study eligibility following community-based recruitment, 524 participants were randomized to either no incentive (N = 180), incentives (N = 172), or deposit contracts (N = 172): median age was 25 years (IQR: 22 to 30), 44% were women, and median weekly income was US$13.60 (IQR: US$8.16 to US$21.76). Among participants randomized to deposit contracts, 24/172 (14%) made a baseline deposit, and 2/172 (1%) made a 3-month deposit. In intent-to-treat analyses, HIV retesting at both 3 and 6 months was significantly higher in the incentive arm (89/172 [52%]) than either the control arm (33/180 [18%], odds ratio (OR) 4.8, 95% CI: 3.0 to 7.7, p < 0.001) or the deposit contract arm (28/172 [16%], OR 5.5, 95% CI: 3.3 to 9.1, p < 0.001). Among those in the deposit contract arm who made a baseline deposit, 20/24 (83%) retested at 3 months; 11/24 (46%) retested at both 3 and 6 months. Among 282 participants who retested for HIV during the trial, three (1%; 95%CI: 0.2 to 3%) seroconverted: one in the incentive group and two in the control group. Study limitations include measurement of retesting at the clinic where baseline enrollment occurred, only offering clinic-based (rather than community-based) HIV retesting and lack of measurement of retesting after completion of the trial to evaluate sustained retesting behavior.ConclusionsOffering financial incentives to high-risk adults in Uganda resulted in significantly higher HIV retesting. Deposit contracts had low uptake and overall did not increase retesting. As part of efforts to increase early diagnosis of HIV among high-risk populations, strategic use of incentives to promote retesting should receive greater consideration by HIV programs.Trial registrationclinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02890459","term_id":"NCT02890459"}}NCT02890459.

Gabriel Chamie and colleagues report on a trial of financial incentives for testing in people at risk of HIV infection.     

Offering ART refill through community health workers versus clinic-based follow-up after home-based same-day ART initiation in rural Lesotho: The VIBRA cluster-randomized clinical trial

BackgroundCommunity-based antiretroviral therapy (ART) dispensing by lay workers is an important differentiated service delivery model in sub-Sahara Africa. However, patients new in care are generally excluded from such models. Home-based same-day ART initiation is becoming widespread practice, but linkage to the clinic is challenging. The pragmatic VIBRA (Village-Based Refill of ART) trial compared ART refill by existing lay village health workers (VHWs) versus clinic-based refill after home-based same-day ART initiation.Methods and findingsThe VIBRA trial is a cluster-randomized open-label clinical superiority trial conducted in 249 rural villages in the catchment areas of 20 health facilities in 2 districts (Butha-Buthe and Mokhotlong) in Lesotho. In villages (clusters) randomized to the intervention arm, individuals found to be HIV-positive during a door-to-door HIV testing campaign were offered same-day ART initiation with the option of refill by VHWs. The trained VHWs dispensed drugs and scheduled clinic visits for viral load measurement at 6 and 12 months. In villages randomized to the control arm, participants were offered same-day ART initiation with clinic-based ART refill. The primary outcome was 12-month viral suppression. Secondary endpoints included linkage and 12-month engagement in care. Analyses were intention-to-treat. The trial was registered on ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT03630549","term_id":"NCT03630549"}}NCT03630549). From 16 August 2018 until 28 May 2019, 118 individuals from 108 households in 57 clusters in the intervention arm, and 139 individuals from 130 households in 60 clusters in the control arm, were enrolled (150 [58%] female; median age 36 years [interquartile range 30–48]; 200 [78%] newly diagnosed). In the intervention arm, 48/118 (41%) opted for VHW refill. At 12 months, 46/118 (39%) participants in the intervention arm and 64/139 (46%) in the control arm achieved viral suppression (adjusted risk difference −0.07 [95% CI −0.20 to 0.06]; p = 0.256). Arms were similar in linkage (adjusted risk difference 0.03 [−0.10 to 0.16]; p = 0.630), but engagement in care was non-significantly lower in the intervention arm (adjusted risk difference −0.12 [−0.23 to 0.003]; p = 0.058). Seven and 0 deaths occurred in the intervention and control arm, respectively. Of the intervention participants who did not opt for drug refill from the VHW at enrollment, 41/70 (59%) mentioned trust or conflict issues as the primary reason. Study limitations include a rather small sample size, 9% missing viral load measurements in the primary endpoint window, the low uptake of the VHW refill option in the intervention arm, and substantial migration among the study population.ConclusionsThe offer of village-based ART refill after same-day initiation led to similar outcomes as clinic-based refill. The intervention did not amplify the effect of home-based same-day ART initiation alone. The findings raise concerns about acceptance and safety of ART delivered by lay health workers after initiation in the community.Trial registrationRegistered with Clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT03630549","term_id":"NCT03630549"}}NCT03630549).

Alain Amstutz and co-workers compare village- and clinic-based antiretroviral refills for people with HIV infection in Lesotho.     

Effects of community-based antiretroviral therapy initiation models on HIV treatment outcomes: A systematic review and meta-analysis

BackgroundAntiretroviral therapy (ART) initiation in the community and outside of a traditional health facility has the potential to improve linkage to ART, decongest health facilities, and minimize structural barriers to attending HIV services among people living with HIV (PLWH). We conducted a systematic review and meta-analysis to determine the effect of offering ART initiation in the community on HIV treatment outcomes.Methods and findingsWe searched databases between 1 January 2013 and 22 February 2021 to identify randomized controlled trials (RCTs) and observational studies that compared offering ART initiation in a community setting to offering ART initiation in a traditional health facility or alternative community setting. We assessed risk of bias, reporting of implementation outcomes, and real-world relevance and used Mantel–Haenszel methods to generate pooled risk ratios (RRs) and risk differences (RDs) with 95% confidence intervals. We evaluated heterogeneity qualitatively and quantitatively and used GRADE to evaluate overall evidence certainty. Searches yielded 4,035 records, resulting in 8 included studies—4 RCTs and 4 observational studies—conducted in Lesotho, South Africa, Nigeria, Uganda, Malawi, Tanzania, and Haiti—a total of 11,196 PLWH. Five studies were conducted in general HIV populations, 2 in key populations, and 1 in adolescents. Community ART initiation strategies included community-based HIV testing coupled with ART initiation at home or at community venues; 5 studies maintained ART refills in the community, and 4 provided refills at the health facility. All studies were pragmatic, but in most cases provided additional resources. Few studies reported on implementation outcomes. All studies showed higher ART uptake in community initiation arms compared to facility initiation and refill arms (standard of care) (RR 1.73, 95% CI 1.22 to 2.45; RD 30%, 95% CI 10% to 50%; 5 studies). Retention (RR 1.43, 95% CI 1.32 to 1.54; RD 19%, 95% CI 11% to 28%; 4 studies) and viral suppression (RR 1.31, 95% CI 1.15 to 1.49; RD 15%, 95% CI 10% to 21%; 3 studies) at 12 months were also higher in the community-based ART initiation arms. Improved uptake, retention, and viral suppression with community ART initiation were seen across population subgroups—including men, adolescents, and key populations. One study reported no difference in retention and viral suppression at 2 years. There were limited data on adherence and mortality. Social harms and adverse events appeared to be minimal and similar between community ART initiation and standard of care. One study compared ART refill strategies following community ART initiation (community versus facility refills) and found no difference in viral suppression (RD −7%, 95% CI −19% to 6%) or retention at 12 months (RD −12%, 95% CI −23% to 0.3%). This systematic review was limited by few studies for inclusion, poor-quality observational data, and short-term outcomes.ConclusionsBased on data from a limited set of studies, community ART initiation appears to result in higher ART uptake, retention, and viral suppression at 1 year compared to facility-based ART initiation. Implementation on a wider scale necessitates broader exploration of costs, logistics, and acceptability by providers and PLWH to ensure that these effects are reproducible when delivered at scale, in different contexts, and over time.

Ingrid Eshun-Wilson and co-workers assess the available evidence on community-based treatment initiation for people with HIV.     

Uptake of Home-Based HIV Testing,Linkage to Care,and Community Attitudes about ART in Rural KwaZulu-Natal,South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

BackgroundThe 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.ConclusionsHome-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01509508","term_id":"NCT01509508"}}NCT01509508     

Treatment of W. bancrofti (Wb) in HIV/Wb Coinfections in South India

BackgroundThe disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coincident infections.Conclusions/SignificanceWe were unable to find a significant effect of W. bancrofti infection or its treatment on HIV clinical course or surrogate markers of HIV disease progression though we recognized that our study was limited by the smaller than predicted sample size and by the use of ART in half of the patients. Treatment of W. bancrofti coinfection in HIV positive subjects (as is usual in mass drug administration campaigns) did not represent an increased risk to the subjects, and should therefore be considered for PLWHA living in W. bancrofti endemic areas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00344279","term_id":"NCT00344279"}}NCT00344279     

A Randomized Trial of Time-Limited Antiretroviral Therapy in Acute/Early HIV Infection

Background

It has been proposed that initiation of antiretroviral treatment (ART) very soon after establishment of HIV infection may be beneficial by improving host control of HIV replication and delaying disease progression.

Methods

People with documented HIV infection of less than 12 months’ duration in Baltimore MD and seven Canadian sites were randomized to either a) observation and deferred ART, or b) immediate treatment with ART for 12 months. All subjects not receiving ART were followed quarterly and permanent ART was initiated according to contemporaneous treatment guidelines. The endpoint of the trial was total ART-free time from study entry until initiation of permanent ART.

Results

One hundred thirteen people were randomized, 56 to the observation arm and 57 to the immediate treatment arm. Twenty-three had acute (<2 months) infection and 90 early (2–12 months) infection. Of those randomized to the immediate treatment arm, 37 completed 12 months of ART according to protocol, 9 declined to stop ART after 12 months, and 11 were nonadherent to the protocol or lost to follow-up. Comparing those in the observation arm to either those who completed 12 months of ART or all 56 who were randomized to immediate ART, there was no significant difference between the arms in treatment-free interval after study entry, which was about 18 months in both arms.

Conclusions

This study did not find a benefit from administration of a brief, time-limited (12-month) course of ART in acute or early HIV infection.

Trial Registration

ClinicalTrials.gov NCT00106171     

Integrating HIV services and other health services: A systematic review and meta-analysis

BackgroundIntegration of HIV services with other health services has been proposed as an important strategy to boost the sustainability of the global HIV response. We conducted a systematic and comprehensive synthesis of the existing scientific evidence on the impact of service integration on the HIV care cascade, health outcomes, and cost-effectiveness.Methods and findingsWe reviewed the global quantitative empirical evidence on integration published between 1 January 2010 and 10 September 2021. We included experimental and observational studies that featured both an integration intervention and a comparator in our review. Of the 7,118 unique peer-reviewed English-language studies that our search algorithm identified, 114 met all of our selection criteria for data extraction. Most of the studies (90) were conducted in sub-Saharan Africa, primarily in East Africa (55) and Southern Africa (24). The most common forms of integration were (i) HIV testing and counselling added to non-HIV services and (ii) non-HIV services added to antiretroviral therapy (ART). The most commonly integrated non-HIV services were maternal and child healthcare, tuberculosis testing and treatment, primary healthcare, family planning, and sexual and reproductive health services. Values for HIV care cascade outcomes tended to be better in integrated services: uptake of HIV testing and counselling (pooled risk ratio [RR] across 37 studies: 1.67 [95% CI 1.41–1.99], p < 0.001), ART initiation coverage (pooled RR across 19 studies: 1.42 [95% CI 1.16–1.75], p = 0.002), time until ART initiation (pooled RR across 5 studies: 0.45 [95% CI 0.20–1.00], p = 0.050), retention in HIV care (pooled RR across 19 studies: 1.68 [95% CI 1.05–2.69], p = 0.031), and viral suppression (pooled RR across 9 studies: 1.19 [95% CI 1.03–1.37], p = 0.025). Also, treatment success for non-HIV-related diseases and conditions and the uptake of non-HIV services were commonly higher in integrated services. We did not find any significant differences for the following outcomes in our meta-analyses: HIV testing yield, ART adherence, HIV-free survival among infants, and HIV and non-HIV mortality. We could not conduct meta-analyses for several outcomes (HIV infections averted, costs, and cost-effectiveness), because our systematic review did not identify sufficient poolable studies. Study limitations included possible publication bias of studies with significant or favourable findings and comparatively weak evidence from some world regions and on integration of services for key populations in the HIV response.ConclusionsIntegration of HIV services and other health services tends to improve health and health systems outcomes. Despite some scientific limitations, the global evidence shows that service integration can be a valuable strategy to boost the sustainability of the HIV response and contribute to the goal of ‘ending AIDS by 2030’, while simultaneously supporting progress towards universal health coverage.

Caroline Bulstra and co-workers assess evidence on the benefits of service integration in the HIV care cascade.     

Uptake,Accuracy, Safety,and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre,Malawi: A Community-Based Prospective Study

BackgroundHome-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population.ConclusionsCommunity-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.     

Monetary incentives and peer referral in promoting secondary distribution of HIV self-testing among men who have sex with men in China: A randomized controlled trial

BackgroundDigital network–based methods may enhance peer distribution of HIV self-testing (HIVST) kits, but interventions that can optimize this approach are needed. We aimed to assess whether monetary incentives and peer referral could improve a secondary distribution program for HIVST among men who have sex with men (MSM) in China.Methods and findingsBetween October 21, 2019 and September 14, 2020, a 3-arm randomized controlled, single-blinded trial was conducted online among 309 individuals (defined as index participants) who were assigned male at birth, aged 18 years or older, ever had male-to-male sex, willing to order HIVST kits online, and consented to take surveys online. We randomly assigned index participants into one of the 3 arms: (1) standard secondary distribution (control) group (n = 102); (2) secondary distribution with monetary incentives (SD-M) group (n = 103); and (3) secondary distribution with monetary incentives plus peer referral (SD-M-PR) group (n = 104). Index participants in 3 groups were encouraged to order HIVST kits online and distribute to members within their social networks. Members who received kits directly from index participants or through peer referral links from index MSM were defined as alters. Index participants in the 2 intervention groups could receive a fixed incentive ($3 USD) online for the verified test result uploaded to the digital platform by each unique alter. Index participants in the SD-M-PR group could additionally have a personalized peer referral link for alters to order kits online. Both index participants and alters needed to pay a refundable deposit ($15 USD) for ordering a kit. All index participants were assigned an online 3-month follow-up survey after ordering kits. The primary outcomes were the mean number of alters motivated by index participants in each arm and the mean number of newly tested alters motivated by index participants in each arm. These were assessed using zero-inflated negative binomial regression to determine the group differences in the mean number of alters and the mean number of newly tested alters motivated by index participants. Analyses were performed on an intention-to-treat basis. We also conducted an economic evaluation using microcosting from a health provider perspective with a 3-month time horizon. The mean number of unique tested alters motivated by index participants was 0.57 ± 0.96 (mean ± standard deviation [SD]) in the control group, compared with 0.98 ± 1.38 in the SD-M group (mean difference [MD] = 0.41),and 1.78 ± 2.05 in the SD-M-PR group (MD = 1.21). The mean number of newly tested alters motivated by index participants was 0.16 ± 0.39 (mean ± SD) in the control group, compared with 0.41 ± 0.73 in the SD-M group (MD = 0.25) and 0.57 ± 0.91 in the SD-M-PR group (MD = 0.41), respectively. Results indicated that index participants in intervention arms were more likely to motivate unique tested alters (control versus SD-M: incidence rate ratio [IRR = 2.98, 95% CI = 1.82 to 4.89, p-value < 0.001; control versus SD-M-PR: IRR = 3.26, 95% CI = 2.29 to 4.63, p-value < 0.001) and newly tested alters (control versus SD-M: IRR = 4.22, 95% CI = 1.93 to 9.23, p-value < 0.001; control versus SD-M-PR: IRR = 3.49, 95% CI = 1.92 to 6.37, p-value < 0.001) to conduct HIVST. The proportion of newly tested testers among alters was 28% in the control group, 42% in the SD-M group, and 32% in the SD-M-PR group. A total of 18 testers (3 index participants and 15 alters) tested as HIV positive, and the HIV reactive rates for alters were similar between the 3 groups. The total costs were $19,485.97 for 794 testers, including 450 index participants and 344 alter testers. Overall, the average cost per tester was $24.54, and the average cost per alter tester was $56.65. Monetary incentives alone (SD-M group) were more cost-effective than monetary incentives with peer referral (SD-M-PR group) on average in terms of alters tested and newly tested alters, despite SD-M-PR having larger effects. Compared to the control group, the cost for one more alter tester in the SD-M group was $14.90 and $16.61 in the SD-M-PR group. For newly tested alters, the cost of one more alter in the SD-M group was $24.65 and $49.07 in the SD-M-PR group. No study-related adverse events were reported during the study. Limitations include the digital network approach might neglect individuals who lack internet access.ConclusionsMonetary incentives alone and the combined intervention of monetary incentives and peer referral can promote the secondary distribution of HIVST among MSM. Monetary incentives can also expand HIV testing by encouraging first-time testing through secondary distribution by MSM. This social network–based digital approach can be expanded to other public health research, especially in the era of the Coronavirus Disease 2019 (COVID-19).Trial registrationChinese Clinical Trial Registry (ChiCTR) ChiCTR1900025433

Yi Zhou and colleagues investigate whether monetary incentives and peer referral could improve a secondary distribution program for HIV self-testing among men who have sex with men in China.     

Effectiveness of a primary care-based integrated mobile health intervention for stroke management in rural China (SINEMA): A cluster-randomized controlled trial

BackgroundManaging noncommunicable diseases through primary healthcare has been identified as the key strategy to achieve universal health coverage but is challenging in most low- and middle-income countries. Stroke is the leading cause of death and disability in rural China. This study aims to determine whether a primary care-based integrated mobile health intervention (SINEMA intervention) could improve stroke management in rural China.Methods and findingsBased on extensive barrier analyses, contextual research, and feasibility studies, we conducted a community-based, two-arm cluster-randomized controlled trial with blinded outcome assessment in Hebei Province, rural Northern China including 1,299 stroke patients (mean age: 65.7 [SD:8.2], 42.6% females, 71.2% received education below primary school) recruited from 50 villages between June 23 and July 21, 2017. Villages were randomly assigned (1:1) to either the intervention or control arm (usual care). In the intervention arm, village doctors who were government-sponsored primary healthcare providers received training, conducted monthly follow-up visits supported by an Android-based mobile application, and received performance-based payments. Participants received monthly doctor visits and automatically dispatched daily voice messages. The primary outcome was the 12-month change in systolic blood pressure (BP). Secondary outcomes were predefined, including diastolic BP, health-related quality of life, physical activity level, self-reported medication adherence (antiplatelet, statin, and antihypertensive), and performance in “timed up and go” test. Analyses were conducted in the intention-to-treat framework at the individual level with clusters and stratified design accounted for by following the prepublished statistical analysis plan. All villages completed the 12-month follow-up, and 611 (intervention) and 615 (control) patients were successfully followed (3.4% lost to follow-up among survivors). The program was implemented with high fidelity, and the annual program delivery cost per capita was US$24.3. There was a significant reduction in systolic BP in the intervention as compared with the control group with an adjusted mean difference: −2.8 mm Hg (95% CI −4.8, −0.9; p = 0.005). The intervention was significantly associated with improvements in 6 out of 7 secondary outcomes in diastolic BP reduction (p < 0.001), health-related quality of life (p = 0.008), physical activity level (p < 0.001), adherence in statin (p = 0.003) and antihypertensive medicines (p = 0.039), and performance in “timed up and go” test (p = 0.022). We observed reductions in all exploratory outcomes, including stroke recurrence (4.4% versus 9.3%; risk ratio [RR] = 0.46, 95% CI 0.32, 0.66; risk difference [RD] = 4.9 percentage points [pp]), hospitalization (4.4% versus 9.3%; RR = 0.45, 95% CI 0.32, 0.62; RD = 4.9 pp), disability (20.9% versus 30.2%; RR = 0.65, 95% CI 0.53, 0.79; RD = 9.3 pp), and death (1.8% versus 3.1%; RR = 0.52, 95% CI 0.28, 0.96; RD = 1.3 pp). Limitations include the relatively short study duration of only 1 year and the generalizability of our findings beyond the study setting.ConclusionsIn this study, a primary care-based mobile health intervention integrating provider-centered and patient-facing technology was effective in reducing BP and improving stroke secondary prevention in a resource-limited rural setting in China.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03185858","term_id":"NCT03185858"}}NCT03185858.

Lijing Yan and colleagues evaluate a mobile health intervention for secondary stroke prevention in China.     

The revolving door of HIV care: Revising the service delivery cascade to achieve the UNAIDS 95-95-95 goals

Peter Ehrenkranz and co-authors present a cyclical cascade of care for people with HIV infection, aiming to facilitate assessment of outcomes.

Summary points

• Antiretroviral therapy (ART) for human immunodeficiency virus (HIV) prevents illness and death from HIV disease and transmission of HIV infection. To encourage global scale-up of ART, the Joint UN Program on HIV/AIDS (UNAIDS) issued the “95-95-95” targets for the HIV “cascade of care.” These targets state that by 2030, 95% of individuals living with HIV will know their HIV status, 95% of people with diagnosed HIV infection will receive ART, and 95% of those taking ART will have achieved suppression of the virus.
• While tremendous progress has been made toward achieving these targets, substantial gaps remain. The challenge of closing the final gaps requires reconsideration of the cascade itself.
• The 95-95-95 HIV care cascade depicts a linear and unidirectional continuum of care with one starting point (HIV diagnosis) and one ending point (treatment discontination or death). This simplification of the cascade oversimplifies the complex cycle of engagement, disengagement, temporary disuptions, reengagement, and transitions in care experienced by many people living with HIV (PLHIV).
• As the proportion of PLHIV who reinitiate ART after previously starting and stopping increases, we propose to update the HIV cascade of care to better reflect actual experiences of PLHIV. The new cascade makes the cycle of engaging and reengaging in HIV care both explicit and expected.
• The revised cascade will inform and prioritize efforts by communities, healthcare workers, implementers, program managers, policymakers, and donors to prevent missed clinic visits, overcome barriers to care reentry, and minimize onset of advanced HIV disease. It will also emphasize that morbidity, mortality, and onward transmission can be minimized by focusing interventions on anticipating, and then reducing, the duration of gaps in care.

     

Postpartum depressive symptoms following implementation of the 10 steps to successful breastfeeding program in Kinshasa,Democratic Republic of Congo: A cohort study

BackgroundSocial support and relevant skills training can reduce the risk of postpartum depression (PPD) by reducing the impact of stressors. The 10-step program to encourage exclusive breastfeeding that forms the basis of the Baby-Friendly Hospital Initiative (BFHI) provides both, suggesting it may lessen depressive symptoms directly or by reducing difficulties associated with infant feeding. Our objective was to quantify the association of implementing Steps 1–9 or Steps 1–10 on postpartum depressive symptoms and test whether this association was mediated by breastfeeding difficulties.Methods and findingsWe used data from a breastfeeding promotion trial of all women who gave birth to a healthy singleton between May 24 and August 25, 2012 in 1 of the 6 facilities comparing different BFHI implementations (Steps 1–9, Steps 1–10) to the standard of care (SOC) randomized by facility in Kinshasa, Democratic Republic of Congo. Depressive symptoms, a non-registered trial outcome, was assessed at 14 weeks via the Edinburgh Postnatal Depression Scale (EPDS). Inverse probability weighting (IPW) was used to estimate the association of BFHI implementations on depressive symptoms and the controlled direct association through breastfeeding difficulties at 10 weeks postpartum.A total of 903 mother–infant pairs were included in the analysis. Most women enrolled had previously given birth (76%) and exclusively breastfed at 10 weeks (55%). The median age was 27 (interquartile range (IQR): 23, 32 years). The proportion of women reporting breastfeeding difficulties at week 10 was higher in both Steps 1–9 (75%) and Steps 1–10 (91%) relative to the SOC (67%). However, the number of reported difficulties was similar between Steps 1–9 (median: 2; IQR: 0, 3) and SOC (2; IQR: 0, 3), with slightly more in Steps 1–10 (2; IQR: 1, 3). The prevalence of symptoms consistent with probable depression (EPDS score >13) was 18% for SOC, 11% for Steps 1–9 (prevalence difference [PD] = −0.08; 95% confidence interval (CI): −0.14 to −0.01, p = 0.019), and 8% for Steps 1–10 (PD = −0.11, −0.16 to −0.05; p < 0.001). We found mediation by breastfeeding difficulties. In the presence of any difficulties, the PD was reduced for both Steps 1–9 (−0.15; 95% confidence level (CL): −0.25, −0.06; p < 0.01) and Steps 1–10 (−0.16; 95% CL: −0.25, −0.06; p < 0.01). If no breastfeeding difficulties occurred in the population, there was no difference in the prevalence of probable depression for Steps 1–9 (0.21; 95% CL: −0.24, 0.66; p = 0.365) and Steps 1–10 (−0.03; 95% CL: −0.19, 0.13; p = 0.735). However, a limitation of the study is that the results are based on 2 hospitals randomized to each group.ConclusionsIn conclusion, in this cohort, the implementation of the BFHI steps was associated with a reduction in depressive symptoms in the groups implementing BFHI Steps 1–9 or 1–10 relative to the SOC, with the implementation of Steps 1–10 associated with the largest decrease. Specifically, the reduction in depressive symptoms was observed for women reporting breastfeeding difficulties. PPD has a negative impact on the mother, her partner, and the baby, with long-lasting consequences. This additional benefit of BFHI steps suggests that renewed effort to scale its implementation globally may be beneficial to mitigate the negative impacts of PPD on the mother, her partner, and the baby.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01428232","term_id":"NCT01428232"}}NCT01428232

In a cohort study, Robert Agler and colleagues investigate the associations between postnatal depression symptoms and implementation of a Baby-Friendly Hospital Initiative in Kinshasa, Democratic Republic of Congo.     

HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

Background

The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence.

Methods and Findings

The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence.We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data.We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence.

Conclusions

The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.     

A Randomized,Controlled, Trial of Short Cycle Intermittent Compared to Continuous Antiretroviral Therapy for the Treatment of HIV Infection in Uganda

Background

Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs.

Methods

A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count ≥125 cells/mm³ and HIV RNA plasma levels <50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection.

Results

Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39).

Conclusions

Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00339456","term_id":"NCT00339456"}}NCT00339456     

Impact of Early Initiation of Antiretroviral Therapy in Patients with Acute HIV Infection in Vienna,Austria

BackgroundIt is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART.MethodsWe retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis.ResultsAmong the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004).ConclusionsInitiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits.     

Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial

BackgroundLow syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China.Methods and findingsAn open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing.ConclusionsCompared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested).Trial registrationChinese Clinical Trial Registry: ChiCTR1900022409.

In a multi-arm randomized controlled trial, Cheng Wang and colleagues determine the effectiveness and cost of expanding syphilis self testing among men who have sex with men in China.