A pilot project harnessing surveillance systems to support clinicians providing clinical care for people diagnosed with hepatitis C in Victoria, Australia, September 2021 to 31 March 2022.

BackgroundActive follow-up of chronic hepatitis C notifications to promote linkage to care is a promising strategy to support elimination.AimThis pilot study in Victoria, Australia, explored if the Department of Health could follow-up on hepatitis C cases through their diagnosing clinicians, to assess and support linkage to care and complete data missing from the notification.MethodsFor notifications received between 1 September 2021 and 31 March 2022 of unspecified hepatitis C cases (i.e. acquired > 24 months ago or of unknown duration), contact with diagnosing clinicians was attempted. Data were collected on risk exposures, clinical and demographic characteristics and follow-up care (i.e. HCV RNA test; referral or ascertainment of previous negative testing or treatment history). Reasons for unsuccessful doctor contact and gaps in care provision were investigated. Advice to clinicians on care and resources for clinical support were given on demand.ResultsOf 513 cases where information was sought, this was able to be obtained for 356 (69.4%). Reasons for unsuccessful contact included incomplete contact details or difficulties getting in touch across three attempts, particularly for hospital diagnoses. Among the 356 cases, 307 (86.2%) had received follow-up care. Patient-management resources were requested by 100 of 286 contacted diagnosing clinicians.ConclusionsMost doctors successfully contacted had provided follow-up care. Missing contact information and the time taken to reach clinicians significantly impeded the feasibility of the intervention. Enhancing system automation, such as integration of laboratory results, could improve completeness of notifications and support further linkage to care where needed.

Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana.

BACKGROUND: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown. METHODS: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals. RESULTS: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35). CONCLUSIONS: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.).

Reasons for discordance between antiretroviral adherence measures in adolescents.

Adolescents with suboptimal medication taking may deceive caregivers about non-adherence. We conducted a 5-year longitudinal study of adolescents monitored simultaneously with both easily manipulated (e.g., self-report) and hard to manipulate (e.g., microelectronic data) strategies. Adolescents with repeatedly high adherence on the former and low adherence on the latter were invited along with their parental figures ("parents") to participate. We conducted focus groups and semi-structured interviews, separately for adolescents and parents, to elucidate drivers of discordant measures. Forty-seven adolescents and 26 parents participated in focus groups and 4 adolescents were interviewed. Adolescents described hiding pills, discarding pills, and lying. Their motivations included fear of disappointing those who care about them, desire to avoid admonishment by parents and clinic staff, and desire to avoid remedial adherence counseling. Both adolescents and parents considered negative feedback for prior poor adherence to be key motivation to hide current poor adherence from clinic staff. Providing positive feedback for truth-telling, rather than for "evidence" of excellent adherence, might help adolescent patients and their parents to develop stronger treatment alliances with each other and with clinic staff. Such alliances would allow adherence interventions to be better targeted and more fruitful in increasing adherence.

Psychological Reactance is a Novel Risk Factor for Adolescent Antiretroviral Treatment Failure.

Psychological reactance is an aversive response to perceived threats against personal agency. For adolescents receiving HIV treatment in Botswana, we utilized a two-question, medication-specific reactance tool to assess whether: (1) verbal reminders to take medicines made adolescents want to avoid taking them, and, (2) whether adolescents felt anger when reminded to take medicines. Reactant adolescents had 2.05-fold (95% CI 1.23, 3.41) greater odds of treatment failure than non-reactant adolescents (p = 0.03). Adjusted risk of treatment failure was 14% (95% CI 3%, 28%) greater for each point elevation in reactance score (p = 0.016). Autonomy over medication-taking did not modify the association between reactance and treatment failure. Psychological reactance may be a useful interventional target for improving adolescent adherence.

Gaps in the HIV diagnosis and care cascade for migrants in Australia, 2013-2017: A cross-sectional study.

BACKGROUND: Globally, few studies compare progress toward the Joint United Nations Program on HIV/AIDS (UNAIDS) Fast-Track targets among migrant populations. Fast-Track targets are aligned to the HIV diagnosis and care cascade and entail achieving 90-90-90 (90% of people living with HIV [PLHIV] diagnosed, 90% of those diagnosed on treatment, and 90% of those on treatment with viral suppression [VS]) by 2020 and 95-95-95 by 2030. We compared cascades between migrant and nonmigrant populations in Australia. METHODS AND FINDINGS: We conducted a serial cross-sectional survey for HIV diagnosis and care cascades using modelling estimates for proportions diagnosed combined with a clinical database for proportions on treatment and VS between 2013-2017. We estimated the number of PLHIV and number diagnosed using New South Wales (NSW) and Victorian (VIC) data from the Australian National HIV Registry. Cascades were stratified by migration status, sex, HIV exposure, and eligibility for subsidised healthcare in Australia (reciprocal healthcare agreement [RHCA]). We found that in 2017, 17,760 PLHIV were estimated in NSW and VIC, and 90% of them were males. In total, 90% of estimated PLHIV were diagnosed. Of the 9,391 who were diagnosed and retained in care, most (85%; n = 8,015) were males. We excluded 38% of PLHIV with missing data for country of birth, and 41% (n = 2,408) of eligible retained PLHIV were migrants. Most migrants were from Southeast Asia (SEA; 28%), northern Europe (12%), and eastern Asia (11%). Most of the migrants and nonmigrants were males (72% and 83%, respectively). We found that among those retained in care, 90% were on antiretroviral therapy (ART), and 95% of those on ART had VS (i.e., 90-90-95). Migrants had larger gaps in their HIV diagnosis and care cascade (85-85-93) compared with nonmigrants (94-90-96). Similarly, there were larger gaps among migrants reporting male-to-male HIV exposure (84-83-93) compared with nonmigrants reporting male-to-male HIV exposure (96-92-96). Large gaps were also found among migrants from SEA (72-87-93) and sub-Saharan Africa (SSA; 89-93-91). Migrants from countries ineligible for RHCA had lower cascade estimates (83-85-92) than RHCA-eligible migrants (96-86-95). Trends in the HIV diagnosis and care cascades improved over time (2013 and 2017). However, there was no significant increase in ART coverage among migrant females (incidence rate ratio [IRR]: 1.03; 95% CI 0.99-1.08; p = 0.154), nonmigrant females (IRR: 1.01; 95% CI 0.95-1.07; p = 0.71), and migrants from SEA (IRR: 1.03; 95% CI 0.99-1.07; p = 0.06) and SSA (IRR: 1.03; 95% CI 0.99-1.08; p = 0.11). Additionally, there was no significant increase in VS among migrants reporting male-to-male HIV exposure (IRR: 1.02; 95% CI 0.99-1.04; p = 0.08). The major limitation of our study was a high proportion of individuals missing data for country of birth, thereby limiting migrant status categorisation. Additionally, we used a cross-sectional instead of a longitudinal study design to develop the cascades and used the number retained as opposed to using all individuals diagnosed to calculate the proportions on ART. CONCLUSIONS: HIV diagnosis and care cascades improved overall between 2013 and 2017 in NSW and VIC. Cascades for migrants had larger gaps compared with nonmigrants, particularly among key migrant populations. Tracking subpopulation cascades enables gaps to be identified and addressed early to facilitate achievement of Fast-Track targets.

Pharmacy Refill Data are Poor Predictors of Virologic Treatment Outcomes in Adolescents with HIV in Botswana.

In adults living with HIV, pharmacy refill data are good predictors of virologic failure (VF). The utility of pharmacy refill data for predicting VF in adolescents has not been reported. We evaluated data from 291 adolescents on antiretroviral therapy. The main outcome measure was VF, defined as two consecutive HIV viral load measurements ≥ 400 copies/mL during 24-months of follow-up. Pharmacy refill non-adherence was defined as two consecutive refill adherence measurements < 95% during the same period. Fifty-three (18%) adolescents experienced VF. One hundred twenty-eight (44%) adolescents had refill non-adherence. Refill non-adherence had poor discriminative ability for indicating VF (receiver operating characteristic AUC = 0.60). Sensitivity and specificity for predicting VF was poor (60% (95% CI 46-74%) and 60% (95% CI 53-66%), respectively). The lack of a viable surrogate for VF in adolescents highlights the urgent need for more access to virologic testing and novel methods of monitoring adolescent treatment adherence.

Distinctive barriers to antiretroviral therapy adherence among non-adherent adolescents living with HIV in Botswana.

Levels of adherence to HIV treatment are lower among adolescents compared with older and younger individuals receiving similar therapies. We purposely sampled the most and least adherent adolescents from a 300-adolescent longitudinal HIV treatment adherence study in Gaborone, Botswana. Multiple objective and subjective measures of adherence were available and study participants were selected based on sustained patterns of either excellent or poor adherence over a one-year period. Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with the adolescents and a subset of their caregivers with the goal of revealing barriers and facilitators of adherence. Focus groups were segregated by adherence classification of the participants. Following coding of transcripts, matrices were developed based on participants' adherence classifications in order to clarify differences in themes generated by individuals with different adherence characteristics. 47 adolescents and 25 adults were included. The non-adherent adolescents were older than the adherent adolescents (median age 18 years (IQR 16-19) vs. 14 years (IQR 12-15 years)), with median time on treatment near 10 years in both groups. Interference with daily activities, concerns about stigma and discrimination, side effects, denial of HIV status, and food insecurity arose as challenges to adherence among both those who were consistently adherent and those who were poorly-adherent to their medications. Low outcome expectancy, treatment fatigue, mental health and substance use problems, and mismatches between desired and received social support were discussed only among poorly adherent adolescents and their caregivers. Challenges raised only among adolescents and caregivers in the non-adherent groups are hypothesis-generating, identifying areas that may have a greater contribution to poor outcomes than challenges faced by both adherent and non-adherent adolescents. The contribution of these factors to poor outcomes should be explored in future studies.

Patterns of HIV Treatment Adherence do not Differ Between Male and Female Adolescents in Botswana.

We hypothesized that longer and more frequent dosing gaps among boys in Botswana taking antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection compared to girls could account for previously seen gender-specific differences in outcomes. We monitored 154 male and 134 female adolescents for 2 years with medication event monitoring systems (MEMS). Median adherence was 95.6 % for males and 95.7 % for females (p = 0.40). There were no significant gender differences in the number of ≥7 day (p = 0.55) and ≥14 day (p = 0.48) dosing gaps. The median maximal gap was 7.7 days for males and 8.0 days for females (p = 0.47). These findings are not consistent with clinically meaningful gender differences in adherence.

Prediction of HIV Virologic Failure Among Adolescents Using the Pediatric Symptom Checklist.

Psychosocial dysfunction is a risk factor for treatment non-adherence among children and adolescents. A previous study showed that high scores on the Pediatric Symptom Checklist (PSC) were associated with a history of HIV virologic failure. We assessed whether high scores on the PSC could predict virologic failure in HIV-infected youth. Caregivers of 234 adolescents between the ages of 10 and 16 years were asked to complete a PSC at baseline. Elevated PSC scores were associated with virologic failure in the subsequent 6 months. PSC scores may help guide resource utilization when viral load monitoring is limited.

The adherence-outcome relationship is not altered by diary-driven adjustments of microelectronic monitor data.

PURPOSE: The purpose of this study was to determine whether diary-driven adjustment of Medication Event Monitoring System (MEMS) data based on Supporting Information strengthens the relationship between measured antiretroviral medication adherence and plasma HIV viral load (VL). METHODS: HIV+ adolescents on antiretroviral treatment were monitored with MEMS for 30 days preceding a VL measurement. The primary outcome was VL ≥ 400 copies/mL. Handwritten diaries were used to comprehensively record deviations from recommended use (bottle opened but dose not taken or bottle not opened and dose taken). Data were adjusted ("cleaned") based on diary events. Data were "capped" at the prescribed number of doses/day. Receiver operator characteristic analysis compared the relationships between (i) raw MEMS data, (ii) diary-cleaned, (iii) capped, or (iv) cleaned and capped MEMS data and VL. RESULTS: Over 30 days preceding VL measurements, 273 adolescents had 465 diary events. Capping resulted in fewer patients classified as 95% adherent (65.2%) compared with raw data (71.4%), p < 0.001. Adherence was highly associated with VL (OR 1.05, p < 0.001). The area under the receiver operating characteristic curve for continuous adherence compared with VL was 0.89 (95%CI: 0.82-0.95). Neither diary-cleaning, capping, nor cleaning and capping MEMS data significantly altered the association between adherence and VL (p = 0.14, 0.40, and 0.19, respectively). CONCLUSION: Medication Event Monitoring System data-cleaning based on diary entries did not affect the adherence-VL relationship.

High prevalence of pre-treatment and acquired HIV-1 drug resistance mutations among non-citizens living with HIV in Botswana.

Background: Approximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana. Methods: A total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019-2021. Viral RNA isolated from plasma samples were genotyped for HIV drug resistance (HIVDR) using Sanger sequencing. Major known HIV drug resistance mutations (DRMs) in the pol region were determined using the Stanford HIV Drug Resistance Database. The proportions of HIV DRMs amongst TE and TN non-citizens were estimated with 95% confidence intervals (95% CI) and compared between the two groups. Results: A total of 60/152 (39.5%) participants had a detectable viral load (VL) >40 copies/mL and these were included in the subsequent analyses. The median age at enrollment was 43 years (Q1, Q3: 38-48). Among individuals with VL > 40 copies/mL, 60% (36/60) were treatment-experienced with 53% (19/36) of them on Atripla. Genotyping had a 62% (37/60) success rate - 24 were TE, and 13 were TN. A total of 29 participants (78.4, 95% CI: 0.12-0.35) had major HIV DRMs, including at least one non-nucleoside reverse transcriptase inhibitor (NNRTI) associated DRM. In TE individuals, ADR to any antiretroviral drug was 83.3% (20/24), while for PDR was 69.2% (9/13). The most frequent DRMs were nucleoside reverse transcriptase inhibitors (NRTIs) M184V (62.1%, 18/29), NNRTIs V106M (41.4%, 12/29), and K103N (34.4%, 10/29). No integrase strand transfer inhibitor-associated DRMs were reported. Conclusion: We report high rates of PDR and ADR in ART-experienced and ART-naïve non-citizens, respectively, in Botswana. Given the uncertainty of time of HIV acquisition and treatment adherence levels in this population, routine HIV-1C VL monitoring coupled with HIVDR genotyping is crucial for long-term ART success.

Connecting patients notified with hepatitis C to treatment (CONNECT Study): A randomized controlled trial of active case management by a health department to support primary care practitioners.

BACKGROUND: Despite subsidised access to direct-acting antivirals (DAAs), hepatitis C (HCV) treatment uptake in Australia is declining. Interventions are needed to link people living with HCV to care and treatment. We implemented and measured effectiveness of a state-wide, health department-led, enhanced case management through the primary care practitioner for all HCV notifications, aiming to encourage and support treatment commencement. METHODS: A randomised controlled trial compared enhanced case management, delivered by the health department to diagnosing clinicians, with standard of care using notifiable disease systems in Tasmania, Australia (2020-21). The intervention involved a nurse specialist contacting and providing support by telephone to primary care practitioners making an HCV notification. The primary outcome was the proportion of cases notified with chronic hepatitis C who commenced treatment within 12 weeks of notification. We allowed a 12-week extended follow-up period at the end of the study for participants with no outcomes. RESULTS: Eighty-five primary care practitioners randomised to the intervention and 86 to standard of care arms notified 111 and 115 HCV cases, respectively. The proportion of cases notified with chronic hepatitis (HCV RNA detected) commencing treatment within 12 weeks was similar between study arms (41% vs 33%; p=0·51) and after extended study follow-up (65% vs 48%; p=0·18). RNA test completion was higher in the intervention than in standard of care arm (89% vs. 78%; p=0·03), while completing pre-treatment workup for chronic patients (65% vs. 64%; p=0·93) was similar. CONCLUSION: This was the first prospective randomised study of the utility of immediate HCV notification follow-up of primary care practitioners to enhance treatment uptake using disease notification surveillance data. We demonstrated improvement in HCV RNA testing and trend toward better engagement in care, but no significant increase in treatment uptake.

Male circumcision uptake during the Botswana Combination Prevention Project.

INTRODUCTION: Voluntary medical male circumcision (VMMC) uptake has been slow in some countries, including Botswana. To inform demand creation efforts, we examined sociodemographic characteristics and referral procedures associated with VMMC uptake in the Botswana Combination Prevention Project (BCPP) and examined the effectiveness of referral of men to MC services from HIV testing venues. DESIGN: BCPP was a community-randomized trial evaluating the impact of a combination HIV prevention package which included VMMC on community HIV incidence. We conducted a sub-analysis of VMMC uptake in intervention communities. METHODS: During the initial VMMC campaign in 15 intervention communities, baseline male circumcision (MC) status was assessed among men eligible for HIV testing. Uncircumcised male community residents aged 16-49 years with negative/unknown HIV status were mobilized and linked to study VMMC services. Outcomes included MC baseline status and uptake through study services. Univariate and multivariate logistic regressions were performed to identify factors associated with MC uptake. RESULTS: Of 12,864 men eligible for testing, 50% (n = 6,448) were already circumcised. Among the uncircumcised men (n = 6,416), 10% (n = 635) underwent MC. Of the 5,071 men identified as eligible for MC through HIV testing services, 78% declined referral and less than 1% of those were circumcised. Of those accepting referral (n = 1,107), 16% were circumcised. Younger (16-24 years) (aOR: 1.51; 95%CI:1.22,1.85), unemployed men (aOR:1.34; 95%CI: 1.06,1.69), and those undergoing HIV testing at mobile venues (aOR: 1.88; 95%CI: 1.53,2.31) were more likely to get circumcised. Fear of pain was the most prevalent (27%) reason given for not being circumcised. CONCLUSION: Younger, unemployed men seeking HIV testing at mobile sites in Botswana were more likely to get VMMC. Addressing unique barriers for employed and older men may be necessary. Given the simplicity of VMMC as an intervention, the HIV testing programs offer a platform for identifying uncircumcised men and offering information and encouragement to access services.

Randomised controlled trial of active case management to link hepatitis C notifications to treatment in Tasmania, Australia: a study protocol.

INTRODUCTION: By subsidising access to direct acting antivirals (DAAs) for all people living with hepatitis C (HCV) in 2016, Australia is positioned to eliminate HCV as a public health threat. However, uptake of DAAs has declined over recent years and new initiatives are needed to engage people living with HCV in care. Active follow-up of HCV notifications by the health department to the notifying general practitioner (GP) may increase treatment uptake. In this study, we explore the impact of using hepatitis C notifications systems to engage diagnosing GPs and improve patient access to treatment. METHODS AND ANALYSIS: This study is a randomised controlled trial comparing enhanced case management of HCV notifications with standard of care. The intervention includes phone calls from a department of health (DoH) specialist HCV nurse to notifying GPs and offering HCV management support. The level of support requested by the GP was graded in complexity: level 1: HCV information only; level 2: follow-up testing advice; level 3: prescription support including linkage to specialist clinicians and level 4: direct patient contact. The study population includes all GPs in Tasmania who notified HCV diagnosis to the DoH between September 2020 and December 2021. The primary outcome is proportion of HCV cases who initiate DAAs after 12 weeks of HCV notification to the health department. Secondary outcomes are proportion of HCV notifications that complete HCV RNA testing, treatment workup and treatment completion. Multiple logistic regression modelling will explore factors associated with the primary and secondary outcomes. The sample size required to detect a significant difference for the primary outcome is 85 GPs in each arm with a two-sided alpha of 0.05% and 80% power. ETHICS AND DISSEMINATION: The study was approved by University of Tasmania's Human Research Ethics Committee (Protocol ID: 18418) on 17 December 2019. Results of the project will be presented in scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04510246. TRIAL PROGRESSION: The study commenced recruitment in September 2020 and end of study expected December 2021.

"It's time!": A qualitative exploration of the acceptability of hepatitis C notification systems to help eliminate hepatitis C.

BACKGROUND: In Australia, the unrestricted and subsidised availability of direct-acting antivirals for people living with hepatitis C has made the elimination of hepatitis C possible. Recent declining treatment uptake, however, may jeopardise the attainment of this goal. Notification data already exist in many jurisdictions but are presently under-utilised. Despite growing interest in the potential use of data to link people diagnosed with hepatitis C to treatment services, little evidence exists on the acceptability and feasibility of this approach. Our study aimed to address this gap and guide future strategies to enhance treatment uptake. METHODS: Twenty-seven people with lived experience of injecting drug use and/or hepatitis C participated in two focus groups exploring views on implementing a system of hepatitis C notification follow-up in Australia, that would direct people to treatment and care. Additionally, qualitative interviews were conducted with 20 key informants to examine the ethical, logistical, and regulatory implications of implementation. Data were thematically analysed using the Theoretical Framework of Acceptability - which has been used to assess the acceptability of interventions from the perspectives of intervention deliverers and recipients. RESULTS: While there were clear reservations, there was consensus that the potential benefits of using notification data to contact people with hepatitis C, outweigh harms. The method of contact (including by whom and how), whether follow-up should include recent versus historical diagnoses, and if record linkage should be used to enhance follow-up were important considerations. Ethical and logistical concerns were raised about the risk that such an approach could exacerbate stigma and discrimination. CONCLUSION: Findings highlight potentially significant benefits of using notifications data to increase access to hepatitis C treatment, a novel approach that can contribute to hepatitis C elimination efforts and prevent hepatitis C-related morbidity and mortality.

To achieve 95-95-95 targets we must reach men and youth: High level of knowledge of HIV status, ART coverage, and viral suppression in the Botswana Combination Prevention Project through universal test and treat approach.

BACKGROUND: Increasing HIV treatment coverage is crucial to reducing population-level HIV incidence. METHODS: The Botswana Combination Prevention Project (BCPP) was a community randomized trial examining the impact of multiple prevention interventions on population-level HIV incidence and was conducted from October 2013 through June 2017. Home and mobile campaigns offered HIV testing to all individuals ≥ age 16. All identified HIV-positive persons who were not on antiretroviral therapy (ART) were referred to treatment and tracked to determine linkage to care, ART status, retention in treatment, and viral suppression. RESULTS: Of an estimated total of 14,270 people living with HIV (PLHIV) residing in the 15 intervention communities, BCPP identified 13,328 HIV-positive persons (93%). At study start, 10,703 (80%) of estimated PLHIV knew their status; 2,625 (20%) learned their status during BCPP, a 25% increase with the greatest increases occurring among men (37%) and youth (77%). At study start, 9,258 (65%) of estimated PLHIV were on ART. An additional 3,001 persons started ART through the study. By study end, 12,259 had initiated and were retained on ART, increasing coverage to 93%. A greater increase in ART coverage was achieved among men (40%) compared to women (29%). Of the 11,954 persons who had viral load (VL) test results, 11,687 (98%) were virally suppressed (HIV-1 RNA ≤400 copies/mL). Overall, 82% had documented VL suppression by study end. CONCLUSIONS: Knowledge of HIV-positive status and ART coverage increased towards 95-95 targets with universal testing, linkage interventions, and ART. The increases in HIV testing and ART use among men and youth were essential to reaching these targets. CLINICAL TRIAL NUMBER: NCT01965470.

Trends in HIV Treatment Adherence Before and After HIV Status Disclosure to Adolescents in Botswana.

PURPOSE: This study aimed to determine if disclosure of HIV status to adolescents impacted their medication adherence and how medication autonomy might explain observed effects. METHODS: Three hundred adolescents on HIV treatment using electronic medication monitors were followed for 24 months while undergoing routine care. One hundred six of the adolescents were HIV disclosure-naïve and HIV status disclosure in this group was assessed quarterly. Analyses included data from the 75 adolescents who experienced disclosure during the study providing adherence and autonomy data both predisclosure and postdisclosure. Segmented generalized estimating equations were used to examine the trend of adherence and autonomy predisclosure and postdisclosure. Covariates assessed include age at disclosure, sex, and orphan status. RESULTS: Median age at study entry was 12.2 years (interquartile range 11.6-12.9). Incident disclosure occurred in 75 (71%) of the adolescents at a median age of 13.1 years (interquartile range 12.5-13.9). Adherence decreased by 11% (95% confidence interval [CI] 7-15, p < .001) during the predisclosure period and by 22% (95% CI 9-36, p = .001) during the postdisclosure period. Adolescents' autonomy over their medication-taking increased over time, but disclosure did not impact the rate of increase in measured medication-taking autonomy. On a scale of 1-4 assessing autonomy (1 = receiving directly observed therapy and 4 = taking medicines mostly without supervision), autonomy increased by an average of .03 units/month (95% CI .02-.03, p < .001) predisclosure and by .05 units/month (95% CI -.01 to .11, p = .42) postdisclosure. CONCLUSIONS: The findings suggest that, among perinatally HIV infected adolescents, HIV status disclosure may adversely impact treatment adherence. Postdisclosure support to HIV infected adolescents should be intensified.

Modelling the impact of migrants on the success of the HIV care and treatment program in Botswana.

INTRODUCTION: Botswana offers publicly financed HIV treatment to citizens, but not migrants, who comprised about 7% of the population in 2016. However, HIV incidence is not declining in proportion to Botswana's HIV response. In 2018, Botswana had 86% of citizens living with HIV diagnosed, 95% of people diagnosed on treatment, and 95% viral suppression among those on treatment. We hypothesised that continued exclusion of migrants is hampering reduction of HIV incidence in Botswana. Hence, we modelled the impact of including migrants in Botswana's HIV response on achieving 90-90-90 and 95-95-95 Fast-Track targets by 2020 and 2030, respectively. METHODS: The Optima HIV model, with demographic, epidemiological, and behavioural inputs, was applied to citizens of and migrants to Botswana. Projections of new HIV infections and HIV-related deaths were compared for three scenarios to the end of 2030: (1) continued status quo for HIV testing and treatment coverage, and maintenance of levels of linkage to care, loss to follow-up, and viral suppression among citizens and migrants (baseline); (2) with scaled-up budget, optimised to achieve 90-90-90 and 95-95-95 Fast-Track targets by 2020 and 2030, respectively, for citizens only; and (3) scaled-up optimised budget to achieve these targets for both citizens and migrants. RESULTS: A baseline of 172,000 new HIV infections and 8,400 HIV-related deaths was projected over 2020-2030. Scaling up to achieve targets among citizens only averted an estimated 48,000 infections and 1,700 deaths. Achieving targets for both citizens and migrants averted 16,000 (34%) more infections and 442 (26%) more deaths. Scaling up for both populations reduced numbers of new HIV infections and deaths by 44% and 39% respectively compared with 2010 levels. Treating migrants when scaling up in both populations was estimated to cost USD 74 million over 2020-2030. CONCLUSIONS: Providing HIV services to migrants in Botswana could lead to further reductions in HIV incidence and deaths. However, even with an increased, optimised budget that achieves 95-95-95 targets for both citizens and migrants by 2030, the 90% incidence reduction target for 2020 will be missed. Further efficiencies and innovations will be needed to meet HIV targets in Botswana.

Advanced HIV disease in the Botswana combination prevention project: prevalence, risk factors, and outcomes.

OBJECTIVE(S): To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4 cell counts ≤200 cells/µl) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes. DESIGN: A subanalysis of a cluster-randomized HIV-prevention trial. HIV status was assessed in 16-64-year-olds through home and mobile testing. All HIV-positive persons not on antiretroviral therapy were referred to local Ministry of Health and Wellness clinics for treatment. METHODS: Analysis was restricted to the 15 intervention clusters. The proportion of individuals with advanced HIV disease was determined; associations between advanced HIV disease and sex and age explored; and rates of viral suppression determined at 1-year. Mortality and retention in care were compared between CD4 strata (CD4 cell counts ≤200 vs. >200 cells/µl). RESULTS: Overall, 17.2% [430/2499; 95% confidence interval (CI) 15.7-18.8%] of study participants had advanced HIV disease (CD4 cell counts ≤200 cells/µl) at time of clinic linkage. Men were significantly more likely to present with CD4 cell counts 200 cells/µl or less than women [23.7 vs. 13.4%, adjusted odds ratio 1.9, 95% CI 1.5-2.3]. The risk of advanced HIV disease increased with increasing age (adjusted odds ratio 2.2, 95% CI 1.4-3.2 >35 vs. <25 years). Patients with CD4 cell counts 200 cells/µl or less had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1-2.1). CONCLUSION: Advanced HIV disease due to late presentation to or disengagement from antiretroviral therapy care remains common in the Treat All era in Botswana, calling for innovative testing, linkage, and treatment strategies to engage and retain harder-to-reach populations in care.

Phylogenetic clustering networks among heterosexual migrants with new HIV diagnoses post-migration in Australia.

BACKGROUND: It is estimated that approximately half of new HIV diagnoses among heterosexual migrants in Victoria, Australia, were acquired post-migration. We investigated the characteristics of phylogenetic clusters in notified cases of HIV among heterosexual migrants. METHODS: Partial HIV pol sequences obtained from routine clinical genotype tests were linked to Victorian HIV notifications with the following exposures listed on the notification form: heterosexual sexual contact, injecting drug use, bisexual sexual contact, male-to male sexual contact or heterosexual sexual contact in combination with injecting drug use, unknown exposure. Those with heterosexual sexual contact as the only exposure were the focus of this study, with the other exposures included to better understand transmission networks. Additional reference sequences were extracted from the Los Alamos database. Maximum likelihood methods were used to infer the phylogeny and the robustness of the resulting tree was assessed using bootstrap analysis. Phylogenetic clusters were defined on the basis of bootstrap and genetic distance. RESULTS: HIV pol sequences were available for 332 of 445 HIV notifications attributed to only heterosexual sexual contact in Victoria from 2005-2014. Forty-three phylogenetic clusters containing at least one heterosexual migrant were detected, 30 (70%) of which were pairs. The characteristics of these phylogenetic clusters varied considerably by cluster size. Pairs were more likely to be composed of people living with HIV from a single country of birth (p = 0.032). Larger clusters (n≥3) were more likely to contain people born in Australian/New Zealand (p = 0.002), migrants from more than one country of birth (p = 0.013) and viral subtype-B, the most common subtype in Australia (p = 0.006). Pairs were significantly more likely to contain females (p = 0.037) and less likely to include HIV diagnoses with male-to-male sexual contact reported as a possible exposure (p<0.001) compared to larger clusters (n≥3). CONCLUSION: Migrants appear to be at elevated risk of HIV acquisition, in part due to intimate relationships between migrants from the same country of origin, and in part due to risks associated with the broader Australian HIV epidemic. However, there was no evidence of large transmission clusters driven by heterosexual transmission between migrants. A multipronged approach to prevention of HIV among migrants is warranted.