Models Of Antiretroviral Therapy Research Articles

Increasing multimonth dispensing of antiretrovirals and assessing the effect on viral load suppression among children and adolescents receiving HIV services in Nigeria.

Multimonth dispensing (MMD) enables less frequent clinic visits and improved outcomes for people living with HIV, but few children and adolescents living with HIV (CALHIV) are on MMD. At the end of the October-December 2019 quarter, only 23% of CALHIV receiving antiretroviral therapy (ART) through SIDHAS project sites in Akwa Ibom and Cross River states, Nigeria, were receiving MMD. In March 2020, during COVID-19, the government expanded MMD eligibility to include children and recommended rapid implementation to minimize clinic visits. SIDHAS provided technical assistance to 36 "high-volume" facilities-≥5 CALHIV on treatment-in Akwa Ibom and Cross River to increase MMD and viral load suppression (VLS) among CALHIV, toward PEPFAR's 80% benchmark for people currently on ART. We present change in MMD, viral load (VL) testing coverage, VLS, optimized regimen coverage, and community-based ART group enrollment among CALHIV from the October-December 2019 quarter (baseline) to January-March 2021 (endline) based on retrospective analysis of routinely collected program data. We compared MMD coverage (primary objective), and optimized regimen coverage, community-based ART group enrollment, VL testing coverage, and VLS (secondary objectives), among CALHIV 18 years and younger pre-/post-intervention (baseline/endline) at the 36 facilities. We excluded children younger than two years, who are not recommended for or routinely offered MMD. The extracted data included age, sex, ART regimen, months of ART dispensed at last refill, most recent VL test results, and community ART group enrollment. Data on MMD-three or more months of ARVs dispensed at one time-were disaggregated into three to five months (3-5-MMD) vs. six or more months (6-MMD). VLS was defined as ≤1,000 copies. We documented MMD coverage by site, optimized regimen, and VL testing and suppression. Using descriptive statistics, we summarized the characteristics of CALHIV on MMD and non-MMD, number of CALHIV on optimized regimens, and proportion enrolled in differentiated service delivery models and community-based ART refill groups. For the intervention, SIDHAS technical assistance was data driven: weekly data analysis/review, site-prioritization scoring, provider mentoring, line listing eligible CALHIV, pediatric regimen calculator, child-optimized regimen transitioning, and community ART models. The proportion of CALHIV ages 2-18 receiving MMD increased from 23% (620/2,647; baseline) to 88% (3,992/4,541; endline), while the proportion of sites reporting suboptimal MMD coverage among CALHIV (<80%) decreased (100% to 28%). In March 2021, 49% of CALHIV were receiving 3-5-MMD and 39% 6-MMD. In October-December 2019, 17%-28% of CALHIV were receiving MMD; by January-March 2021, 99% of those 15-18 years, 94% 10-14 years, 79% 5-9 years, and 71% 2-4 years were on MMD. VL testing coverage remained high (90%), while VLS increased (64% to 92%). The proportion on pediatric-optimized regimens increased (58% to 79%). MMD was feasible among CALHIV without compromising VLS. Expanded eligibility criteria, line listing eligible children, monitoring pediatric antiretroviral stock, and data use contributed to positive results. Future efforts should address low 6-MMD uptake related to stock limitations and synchronize antiretroviral refill pickup with VL sample collection.

Differentiated service delivery for HIV treatment models in Thailand: a cross-sectional assessment of real-world implementation and uptake.

First, to describe the antiretroviral therapy (ART) delivery models available in Thailand to understand differentiated service delivery (DSD) for further service system optimization and expansion of best practices; second, to determine the client characteristics associated with model uptake. Cross-sectional assessment using secondary data to describe ART models implemented as routine services at 4 public hospitals in 3 major provinces with a high HIV burden in Thailand. From April to October 2020, ART clients were screened consecutively according to the inclusion criteria: Thai, aged ≥18 years, and on ART for ≥6 months. HIV treatment models were categorized based on the service type, location, provider, and frequency. Logistic regression was used to identify the associated factors. Seven individual ART delivery models were identified: 4 were facility-based and 3 were out-of-facility. No group models were identified. Of 3,366 records of ART clients reviewed, 3,213 (95.5%) met the study criteria and received ART through the following models: conventional (32.6%), nurse-led clinical consultation (10.0%), fast-track refill (29.0%), after-hours clinic (10.6%), pharmacist-led pickup center (3.6%), key population-led community-based organization (2.7%), and mailing (11.5%). Age, population, duration on ART, and VL were associated with the uptake of certain alternative service models when compared to the conventional model. Among the variety of ART delivery approaches available in Thailand, facility-based models remain the most prevalent. Future work should investigate the role of client preference and choice in choosing service models and service utilization patterns over time, and assess the acceptability and effectiveness of these models.

Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings.

To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through December 2021 among patients on 3L ART from HIV treatment centers in Yaoundé and Douala. Viral load was measured, and genotyping was performed on plasma RNA and proviral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny analysis was performed using MEGA.v7, with P < 0.05 considered significant. Of the 12,093 patients on ART, 53 fully met our inclusion criteria. The median (IQR) age was 51 years (40 to 55 years), and the male/female ratio was 4/5. The median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 months (12 to 32 months), and 15.09% (8/53) were exposed to RAL. The most administered 3L ART was TDF+3TC+DTG+DRV/r (33.96%, 18/53). Only 5.66% (3/53) had unsuppressed viremia (>1000 copies/mL). Resistance testing in proviral DNA was successful for 18/22 participants and revealed 1/18 patients (5.56%, in the RAL-arm) with archived mutations at major resistance positions (G140R and G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18), and F2 (1/18). In Cameroon, 3L-experienced patients had a good virological response with a low level of archived mutations in the integrase. This finding underscored the use of DTG-containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI-resistance, alongside pharmacovigilance. IMPORTANCE We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS' goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens.

Client and healthcare worker experiences with differentiated HIV treatment models in Eswatini.

IntroductionUniversal access to antiretroviral therapy (ART) is a cornerstone of Eswatini’s national HIV strategy, and the number of people on ART in the country more than tripled between 2010 and 2019. Building on these achievements, the Ministry of Health (MOH) is scaling up differentiated service delivery, including less-intensive differentiated ART (DART) models for people doing well on treatment. We conducted a mixed-methods study to explore client and health care worker (HCW) perceptions of DART in Eswatini.MethodsThe study included structured site assessments at 39 purposively selected health facilities (HF), key informant interviews with 20 HCW, a provider satisfaction survey with 172 HCW and a client satisfaction survey with 270 adults.ResultsAll clients had been on ART for more than a year; 69% were on ART for ≥ 5 years. The most common DART models were Fast-Track (44%), Outreach (26%) and Community ART Groups (20%). HCW and clients appreciated DART, noting that the models often decrease provider workload and client wait time. Clients also reported that DART models helped them to adhere to ART, 96% said they were “very satisfied” with their current model, and 90% said they would recommend their model to others, highlighting convenience, efficiency and cost savings. The majority of HCW (52%) noted that implementation of DART reduced their workload, although some models, such as Outreach, were more labor-intensive. Each model had advantages and disadvantages; for example, clients concerned about stigma and inadvertent disclosure of HIV status were less interested in group models.ConclusionsClients in DART models were very satisfied with their care. HCW were also supportive of the new approach to HIV treatment delivery, noting its advantages to HF, HCW and to clients. Given the heterogeneous needs of people living with HIV, no single DART model will suit every client; a diverse portfolio of DART models is likely the best strategy.

The information-motivation-behavioral skills (IMB) model of antiretroviral therapy (ART) adherence among people living with HIV in Shanghai

ABSTRACT The Information-Motivation-Behavioral skills (IMB) model of antiretroviral therapy (ART) adherence was applied in people living with HIV/AIDS in Shanghai, China to understand how adherence-related information, motivation and behavioral skills would affect ART adherence. The LifeWindows Information-Motivation-Behavioral Skills ART Adherence Questionnaire (LW-IMB-AAQ) was translated into Chinese and used. The IMB model was then implemented by testing standardized path estimates with standard model fitness indices in the participants. 426 participants from 11 community centres in Putuo district of Shanghai were recruited, of which 95.3% reported a high level of adherence (>95% adherence). The fitness indices of the final adjusted model were χ2 = 6.110, df = 7, p = 0.527(>0.05), CFI = 1.000(>0.9) and RMSEA = 0.000 (<0.08). In the model, information, which was separated into two sections (the perceived effect of ART on health and knowledge about ART medication), had an indirect effect on the ART adherence through behavioral skills, while motivation did not have such an effect. Neither information nor motivation had a direct effect on ART adherence. In addition, motivation was related to the two sections of information. The feasibility of the IMB model of ART adherence is verified by its application to predictive of adherence-related behaviors among HIV+ patients in this study.

Impact of the COVID-19 pandemic: Community and hospital shared pharmaceutical care model. Satisfaction and acceptability of patients with HIV infection on antiretroviral treatment.

BackgroundThe health crisis due to the COVID-19 pandemic is a challenge in the dispensing of outpatient hospital medication (OHM). Models of Antiretroviral Therapy (ART) based on community pharmacy support (ARTCP) have proven to be successful. The aim was to evaluate the degree of satisfaction, acceptability and limitations of the implementation of ARTCP, in the context of a pandemic, in our environment.MethodsDescriptive cross-sectional study carried out in a Barcelona hospital, during the months of July-November 2020. A telephone survey was carried out via a questionnaire on the quality dimensions of the model (degree of satisfaction, acceptability) and associated inconveniences. Data collected: demographics, antiretroviral treatment (ART), concomitant medication, drug interactions (DDIs), CD4 lymphocyte count and plasma viraemia. Data analysis included descriptive statistics.ResultsA total of 533 (78.0%) HIV patients receiving ART were included. 71.9% (383/533) of these patients were very satisfied and 76.2% preferred attending the community pharmacy rather than the hospital. The mean satisfaction rating was 9.3 (DS: 1.4). The benefits reported were: 1) proximity to home (406: 76.1%); 2) lower risk of contagion of COVID-19 (318: 59.7%); 3) shorter waiting time (201: 37.1%); 4) time flexibility (104: 19.5%); 5) reduction of financial expenses (35: 6.57%). A total of 11 (2%) patients reported no benefit. Only 22.9% reported disadvantages associated with ARTCP: 1) lack of privacy (65: 12.2%); 2) lack of coordination-organization (57: 10.7%).ConclusionThe COVID-19 pandemic has had an impact on the provision of pharmaceutical care for HIV patients. The ARTPC model has proved efficient, with patients reporting a high degree of satisfaction.

Rates of viral suppression in a cohort of people with stable HIV from two community models of ART delivery versus facility-based HIV care in Lusaka, Zambia: a cluster-randomised, non-inferiority trial nested in the HPTN 071 (PopART) trial.

SummaryBackgroundNon-facility-based antiretroviral therapy (ART) delivery for people with stable HIV might increase sustainable ART coverage in low-income and middle-income countries. Within the HPTN 071 (PopART) trial, two interventions, home-based delivery (HBD) and adherence clubs (AC), which included groups of 15–30 participants who met at a communal venue, were compared with standard of care (SoC). In this trial we looked at the effectiveness and feasibility of these alternative models of care. Specifically, this trial aimed to assess whether these models of care had similar virological suppression to that of SoC 12 months after enrolment.MethodsThis was a three-arm, cluster-randomised, non-inferiority trial, done in two urban communities in Lusaka, Zambia included in the HPTN 071 trial. The two communities were split into zones, which were randomly assigned (1:1:1) to the three treatment strategies: 35 zones to the SoC group, 35 zones to the HBD group, and 34 zones to the AC group. ART and adherence support were delivered once every 3 months at home for the HBD group, in groups of 15–30 people in the AC group, or in the clinic for the SoC group. Adults with HIV who were receiving first-line ART for at least 6 months, virally suppressed using national HIV guidelines in the last 12 months, had no other health conditions requiring the clinicians attention, live in the study catchment area, and provided written informed consent, were eligible for inclusion. The primary endpoint was viral suppression at 12 months (with a 6 month final measurement window [ie, 9–15 months]), defined as less than 1000 HIV RNA copies per mL, with a non-inferiority margin of 5%.FindingsBetween May 5 and Dec 19, 2017, 9900 individuals were screened for inclusion, of whom 2489 (25·1%) participants were enrolled into the trial: 781 (31%) in the SoC group, 852 (34%) in the HBD group, and 856 (34%) in the AC group. A higher proportion of participants had viral load measurements in the primary outcome window in the HBD (581 [61%]of 852 participants) and AC (485 [57%] of 856 participants) groups than in the SoC (390 [50%] of 781 patients) group (p=0·0021). Of the 1096 missing observations, 152 (13·8%) were attributable to either deaths (25 [16%] participants), relocations (37 [24%] participants), or lost to follow-up (90 [59%]); 690 (63·0%) participants had viral load results outside the window period; and 254 (23·2%) did not have a viral load result. The prevalence of viral suppression was estimated to be 98·3% (95% CI 96·6 to 99·7) in the SoC group, 98·7% (97·5 to 99·6) in the HBD group, and 99·2% (98·4 to 99·8) in the AC group. This gave an estimated risk difference of 0·3% (95% CI −1·5 to 2·4) for the HBD group compared with the SoC group and 0·9% (−0·8 to 2·8) for the AC group compared with the SoC group. There was strong evidence (p<0·0001) that both community ART models were non-inferior to the SoC group (p<0·0001).InterpretationCommunity models of ART delivery were as effective as facility-based care in terms of viral suppression.FundingNational Institute of Allergy and Infectious Diseases, The International Initiative for Impact Evaluation (3ie), the Bill & Melinda Gates Foundation, National Institute on Drug Abuse, National Institute of Mental Health, and President's Emergency Plan for AIDS Relief.

Acceptability and Preferences of Two Different Community Models of ART Delivery in a High Prevalence Urban Setting in Zambia: Cluster-Randomized Trial, Nested in the HPTN 071 (PopART) Study

Community delivery of Antiretroviral therapy (ART) is a novel innovation to increase sustainable ART coverage for People living with HIV (PLHIV) in resource limited settings. Within a nested cluster-randomised sub-study in two urban communities that participated in the HPTN 071 (PopART) trial in Zambia we investigated individual acceptability and preferences for ART delivery models. Stable PLHIV were enrolled in a cluster-randomized trial of three different models of ART: Facility-based delivery (SoC), Home-based delivery (HBD) and Adherence clubs (AC). Consenting individuals were asked to express their stated preference for ART delivery options. Those assigned to the community models of ART delivery arms could choose (“revealed preference”) between the assigned arm and facility-based delivery. In total 2489 (99.6%) eligible individuals consented to the study and 95.6% chose community models of ART delivery rather than facility-based delivery when offered a choice. When asked to state their preference of model of ART delivery, 67.6% did not state a preference of one model over another, 22.8% stated a preference for HBD, 5.0% and 4.6% stated a preference for AC and SoC, respectively. Offering PLHIV choices of community models of ART delivery is feasible and acceptable with majority expressing HBD as their stated preferred option.

Economic evaluation of differentiated service delivery models for HIV treatment in Lesotho: costs to providers and patients.

IntroductionLesotho, the country with the second‐highest HIV/AIDS prevalence (23.6%) in the world, has made considerable progress towards achieving the “95‐95‐95” UNAIDS targets, but recent success in improving treatment access to all known HIV positive individuals has severely strained existing healthcare infrastructure, financial and human resources. Lesotho also faces the challenge of a largely rural population who incur a significant time and financial burden to visit healthcare facilities. Using data from a cluster‐randomized non‐inferiority trial conducted between August 2017 and July 2019, we evaluated costs to providers and costs to patients of community‐based differentiated models of multi‐month delivery of antiretroviral therapy (ART) in Lesotho.MethodsThe trial of multi‐month dispensing compared 12‐month retention in care among three arms: conventional care, which required quarterly facility visits and ART dispensation (3MF); three‐month community adherence groups (CAGs) (3MC) and six‐month community ART distribution (6MCD). We first estimated the average total annual cost of providing HIV care and treatment followed by the total cost per patient retained 12 months after entry for each arm, using resource utilization data from the trial and local unit costs. We then estimated the average annual cost to patients in each arm with self‐reported questionnaire data.ResultsThe average total annual cost of providing HIV care and treatment per patient was the highest in the 3MF arm ($122.28, standard deviation [SD] $23.91), followed by 3MC ($114.20, SD $23.03) and the 6MCD arm ($112.58, SD $21.44). Per patient retained in care, the average provider cost was $125.99 (SD $24.64) in the 3MF arm and 6% to 8% less for the other two arms ($118.38, SD $23.87 and $118.83, SD $22.63 for the 3MC and 6MCD respectively). There was a large reduction in patient costs for both differentiated service delivery arms: from $44.42 (SD $12.06) annually in the 3MF arm to $16.34 (SD $5.11) annually in the 3MC (63% reduction) and $18.77 (SD $8.31) annually in 6MCD arm (58% reduction).ConclusionsCommunity‐based, multi‐month models of ART in Lesotho are likely to produce small cost savings to treatment providers and large savings to patients in Lesotho. Patient cost savings may support long‐term adherence and retention in care.

A qualitative investigation of HIV treatment dispensing models and impacts on adherence among people living with HIV who use drugs.

Antiretroviral therapy (ART) dispensing is strongly associated with treatment adherence. Among illicit drug-using populations, whom experience greater structural barriers to adherence, directly administered antiretroviral therapy (DAAT) is often regarded as a stronger predictor of optimal adherence over self-administered medications. In Vancouver, Canada, people living with HIV (PLHIV) who use drugs and live in low-income housing are a critical population for treatment support. This group is typically able to access two key DAAT models, daily delivery and daily pickup, in addition to ART self-administration. This ethno-epidemiological qualitative study explores how key dispensing models impact ART adherence among PLHIV who use drugs living in low-income housing, and how this is framed by structural vulnerability. Semi-structured interviews lasting 30–45 minutes were conducted between February and May 2018 with 31 PLHIV who use drugs recruited from an ongoing prospective cohort of PLHIV who use drugs. Interviews were audio-recorded, transcribed verbatim, and analyzed using QSR International’s NVivo 12 software. Interviews focused on housing, drug use, and HIV management. Models that constrained agency were found to have negative impacts on adherence and quality of life. Treatment interruptions were framed by structural vulnerabilities (e.g., housing vulnerability) that impacted ability to maintain adherence under certain dispensing models, and led participants to consider other models. Participants using DAAT models which accounted for their structural vulnerabilities (e.g., mobility issues, housing instability), credited these models for their treatment adherence, but also acknowledged factors that constrained agency, and the negative impacts this could have on both adherence, and quality of life. Being able to integrate ART into an established routine is key to supporting ART adherence. ART models that account for the structural vulnerability of PLHIV who use drugs and live in low-income housing are necessary and housing-based supports could be critical, but the impacts of such models on agency must be considered to ensure optimal adherence.

Community-based delivery of HIV treatment in Zambia: costs and outcomes.

Objective:The aim is to determine the total annual cost per patient treated and total cost per patient retained on antiretroviral therapy in Zambia in conventional care in facilities and across community-based differentiated service delivery (DSD) models.Design:Economic evaluation was conducted using retrospective electronic record review.Twenty healthcare facilities (13 with DSD models and 7 as comparison sites) in six of Zambia's 10 provinces were considered.Methods:All individuals on antiretroviral therapy (ART) >18 years old at the study sites were enrolled in a DSD model or conventional care by site type, respectively, with at least 12 months of follow-up data. Accessing care through DSD models [community adherence groups (CAGs), urban adherence groups (UAGs), home ART delivery and care, and mobile ART services] or facility-based conventional care with 3-monthly visits. Total annual cost per patient treated and the annual cost per patient retained in care 12 months after model enrolment. Retention in care was defined as attending a clinic visit at 12 months ± 3 months.Results:The DSD models assessed cost more per patient/year than conventional care. Costs ranged from an annual $116 to $199 for the DSD models, compared with $100 for conventional care. CAGs and UAGs increased retention by 2 and 14%, respectively. All DSD models cost more per patient retained at 12 months than conventional care. The CAG had the lowest cost/patient retained for DSD models ($140–157).Conclusions:Although they achieve equal or improved retention in care, out-of-facility models of ART were more expensive than conventional care.

First person – Keegan Bush

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Keegan Bush is first author on ‘Drosophila model of anti-retroviral therapy induced peripheral neuropathy and nociceptive hypersensitivity’, published in BiO. Keegan is a PhD Student in the lab of Yogesh Wairkar and Shao-Jun Tang in the departments of Neurology and Neuroscience, and Cell Biology and Anatomy, at Galveston University, Texas, USA, investigating how anti-retroviral drugs cause nociceptive hypersensitivity in people living with HIV.

Alcohol consumption increases non-adherence to ART among people living with HIV enrolled to the community-based care model in rural northern Uganda.

Non-adherence to anti-retroviral therapy (ART) is associated with considerable morbidity and mortality among people living with Human Immunodeficiency Virus (PLHIV). Community-based ART delivery model offers a decentralized and patient-centered approach to care for PLHIV, with the advantage of improved adherence to ART hence good treatment outcomes. However, data are limited on the magnitude of non-adherence to ART among PLHIV enrolled to the community-based ART model of care. In this study, we determined the frequency of non-adherence to ART and the associated factors among PLHIV enrolled to the community-based ART delivery model in a large health facility in rural northern Uganda. This analytic cross-sectional study randomly sampled participants from 21 community drug distribution points at the AIDS Support Organization (TASO) in Gulu district, northern Uganda. Data were collected using a standardized and pre-tested questionnaire, entered in Epi-Data and analyzed in Stata at univariate, bivariate, and multivariate analyses levels. Binary logistic regression analysis was used to determine factors independently associated with non-adherence to ART, reported using odds ratio (OR) and 95% confidence level (CI). The level of statistical significance was 5%. Of 381 participants, 25 (6.6%) were non-adherent to ART and this was significantly associated with alcohol consumption (Adjusted (aOR), 3.24; 95% CI, 1.24-8.34). Other factors namely being single/or never married (aOR, 1.97; 95% CI, 0.62-6.25), monthly income exceeding 27 dollars (aOR, 1.36; 95% CI, 0.52-3.55), being on ART for more than 5 years (aOR, 0.60; 95% CI, 0.23-1.59), receipt of health education on ART side effects (aOR, 0.36; 95% CI, 0.12-1.05), and disclosure of HIV status (aOR, 0.37; 95% CI, 0.04-3.20) were not associated with non-adherence in this setting. Non-adherence to ART was low among PLHIV enrolled to community-based ART delivery model but increases with alcohol consumption. Accordingly, psychosocial support programs should focus on alcohol consumption.

Retention on ART and predictors of disengagement from care in several alternative community-centred ART refill models in rural Swaziland.

IntroductionA broad range of community‐centred care models for patients stable on anti‐retroviral therapy (ART) have been proposed by the World Health Organization to better respond to patient needs and alleviate pressure on health systems caused by rapidly growing patient numbers. Where available, often a single alternative care model is offered in addition to routine clinical care. We operationalized several community‐centred ART delivery care models in one public sector setting. Here, we compare retention in care and on ART and identify predictors of disengagement with care.MethodsPatients on ART were enrolled into three community‐centred ART delivery care models in the rural Shiselweni region (Swaziland), from 02/2015 to 09/2016: Community ART Groups (CAGs), comprehensive outreach care and treatment clubs. We used Kaplan–Meier estimates to describe crude retention in care model and retention on ART (including patients who returned to clinical care). Multivariate Cox proportional hazard models were used to determine factors associated with all‐cause attrition from care model and disengagement with ART.ResultsA total of 918 patients were enrolled. CAGs had the most participants with 531 (57.8%). Median age was 44.7 years (IQR 36.3 to 54.4), 71.8% of patients were female, and 62.6% fulfilled eligibility criteria for community ART. The 12‐month retention in ART was 93.7% overall; it was similar between model types (p = 0.52). A considerable proportion of patients returned from community ART to clinical care, resulting in lower 12 months retention in care model (82.2% overall); retention in care model was lowest in CAGs at 70.4%, compared with 86.3% in outreach and 90.4% in treatment clubs (p < 0.001). In multivariate Cox regression models, patients in CAGs had a higher risk of disengaging from care model (aHR 3.15, 95% CI 2.01 to 4.95, p < 0.001) compared with treatment clubs. We found, however, no difference in attrition in ART between alternative model types.ConclusionsConcurrent implementation of three alternative community‐centred ART models in the same region was feasible. Although a considerable proportion of patients returned back to clinical care, overall ART retention was high and should encourage programme managers to offer community‐centred care models adapted to their specific setting.

A Quantitative Approach to SIV Functional Latency in Brain Macrophages.

Lentiviruses are retroviruses that primarily infect myeloid cells, leading to acute inflammatory infections in many tissues particularly, lung, joints and the central nervous system (CNS). Acute infection by lentiviruses is followed by persistent/latent infections that are not cleared by the host immune system. HIV and SIV are lentiviruses that also infect CD4+ lymphocytes as well as myeloid cells in blood and multiple tissues. HIV infection of myeloid cells in brain, lung and heart cause tissue specific diseases as well as infect cells in gut, lymph nodes and spleen. AIDS dementia and other tissue specific disease are observed when infected individuals are immunosuppressed and the number of circulating CD4+ T cells declines to low levels. Antiretroviral therapy (ART) controls viral spread and dramatically changes the course of immunodeficiency and AIDS dementia. However, ART does not eliminate virus-infected cells. Brain macrophages contain HIV DNA and may represent a latent reservoir that persists. HIV latency in CD4+ lymphocytes is the main focus of current research and concern in efforts to eradicate HIV. However, a number of studies have demonstrated that myeloid cells in blood and tissues of ART suppressed individuals harbor HIV DNA. The resident macrophages in tissues such as brain (microglia), spleen (red pulp macrophages) and alveolar macrophages in lung are derived from the yolk sac and can self renew. The question of the latent myeloid reservoir in HIV has not been rigorously examined and its potential as a barrier to eradication been considered. Using a well characterized SIV ART suppressed, non-human primate (NHP) model, our laboratory developed the first quantitative viral outgrowth assay (QVOA) designed to evaluate latently infected CD4+ lymphocytes and more recently developed a similar protocol for the assessment of latently infected myeloid cells in blood and brain. Using an SIV ART model, it was demonstrated that myeloid cells in blood and brain harbor latent SIV that can be reactivated and produce infectious virus in vitro. These studies demonstrate for the first time that myeloid cells have the potential to be a latent reservoir of HIV that produces infectious virus that can be reactivated in the absence of ART and during HIV eradication strategies. Graphical Abstract.

Providing antiretroviral therapy outside the hospital in a low-resource setting: a pilot study

Abstract Background For nearly three decades, hospitals have been the only source of antiretroviral therapy (ART) for many people living with HIV. Yet, developing countries with the largest burden of HIV commonly lack the hospitals and health-care workers to care for these patients. In 2013, WHO recommended the use of structures outside hospitals for management of HIV. We piloted a community pharmacy ART model in communities with high HIV prevalence in Nigeria. The purpose was to develop a treatment model that could be expanded into an overarching comprehensive response to HIV management, especially in resource-limited settings with weak health systems. Methods Registered community pharmacies linked to participating hospitals were recruited between February 2016 and May 2017. Patients with stable viral loads (≤20 copies/mL) who were willing to have their care devolved to a community pharmacy were referred by trained contact persons at the hospitals. Registered pharmacists at the community pharmacies counselled referred patients and refilled their prescriptions. Biodemographic and clinical data were collected from Feb 25, 2016, to May 31, 2017. The outcome measures were percentage of patients retained in care and adherence to therapy. Mean difference in the viral load at the baseline (≤20 copies/mL) and after 6 months was assessed using a paired sample t-test. Findings 26 community pharmacies and 14 hospitals were included in the pilot. 375 patients (median baseline viral load 19 copies/mL [IQR 19–32]; median CD4 count 460 cells/mL [277–648]) had their care devolved to the community pharmacies. After 12 months, almost all the patients (374 [99·7%] of 375) were retained in care and adherence to medication (measured by prescription refill) was 100%. After 6 months of follow-up, 19 patients received results of their second viral load test, showing no significant difference in the mean viral load between baseline and after 6 months (p Interpretation We show that patients can conveniently access ART in community pharmacies linked to hospitals, with no adverse effects on adherence or viral load. The model will be rolled-out to other regions in Nigeria, and could potentially be applied elsewhere. Funding PEPFAR.

SIV Latency in Macrophages in the CNS.

Lentiviruses infect myeloid cells, leading to acute infection followed by persistent/latent infections not cleared by the host immune system. HIV and SIV are lentiviruses that infect CD4+ lymphocytes in addition to myeloid cells in blood and tissues. HIV infection of myeloid cells in brain, lung, and heart causes tissue-specific diseases that are mostly observed during severe immunosuppression, when the number of circulating CD4+ T cells declines to exceeding low levels. Antiretroviral therapy (ART) controls viral replication but does not successfully eliminate latent virus, which leads to viral rebound once ART is interrupted. HIV latency in CD4+ lymphocytes is the main focus of research and concern when HIV eradication efforts are considered. However, myeloid cells in tissues are long-lived and have not been routinely examined as a potential reservoir. Based on a quantitative viral outgrowth assay (QVOA) designed to evaluate latently infected CD4+ lymphocytes, a similar protocol was developed for the assessment of latently infected myeloid cells in blood and tissues. Using an SIV ART model, it was demonstrated that myeloid cells in blood and brain harbor latent SIV that can be reactivated and produce infectious virus in vitro, demonstrating that myeloid cells have the potential to be an additional latent reservoir of HIV that should be considered during HIV eradication strategies.

Differentiated models of care for postpartum women on antiretroviral therapy in Cape Town, South Africa: a cohort study

Background: The numbers of women initiating lifelong antiretroviral therapy (ART) during pregnancy and postpartum is increasing rapidly, presenting a burden on health systems and an urgent need for scalable models of care for this population. In a pilot project, we referred postpartum women who initiated ART during pregnancy to a community-based model of differentiated ART services.Methods: Eligible women (on ART for at least 3 months with viral load (VL)<1000 copies/mL) were offered a choice of two ART models of care: (i) referral to an existing system of community-based ‘adherence clubs’, operated by lay counsellors with medication collection every 2–4 months; or (ii) referral to local primary healthcare clinics (PHC) with services provided by clinicians and medication collection every 1–2 months (local standard of care for postpartum ART). For evaluation, women were followed through 6-months postpartum with VL testing separate from either ART service.Results: Through September 2015, n = 129 women were enrolled (median age, 28 years; median time postpartum, 10 days). Overall, 65% (n = 84) chose adherence clubs and 35% (n = 45) chose PHCs; there were no demographic or clinical predictors of this choice. Location of service delivery was commonly cited as a reason for choice by women selecting either model of care; shorter waiting times, ability to receive ART from lay counsellors and less frequent appointments were motivations for choosing adherence clubs. Among women choosing adherence clubs, 15% never attended the service and another 11% attended the service but were not retained through six months postpartum. Overall, 86% of women (n = 111) remained in the evaluation through 6 months postpartum; in this group, there were no differences in VL<1000 copies/mL at six months postpartum between women choosing PHCs (88%) vs. adherence clubs (92%; p = 0.483), but women who were not retained in adherence clubs were more likely to have VL≥1000 copies/mL compared to those who remained (p = 0.002).Discussion: Adherence clubs may be a valuable model for postpartum women initiating ART in pregnancy, with good short-term outcomes observed during this critical period. To support optimal implementation, further research is needed into patient preferences for models of care, with consideration of integration of maternal and child health services, while ART adherence and retention require ongoing consideration in this population.

Identifying Key Drivers of the Impact of an HIV Cure Intervention in Sub-Saharan Africa.

Background. It is unknown what properties would be required to make an intervention in low income countries that can eradicate or control human immunodeficiency virus (HIV) without antiretroviral therapy (ART) cost-effective.Methods. We used a model of HIV and ART to investigate the effect of introducing an ART-free viral suppression intervention in 2022 using Zimbabwe as an example country. We assumed that the intervention (cost: $500) would be accessible for 90% of the population, be given to those receiving effective ART, have sufficient efficacy to allow ART interruption in 95%, with a rate of viral rebound of 5% per year in the first 3 months, and a 50% decline in rate with each successive year.Results. An ART-free viral suppression intervention with these properties would result in >0.53 million disability-adjusted-life-years averted over 2022–2042, with a reduction in HIV program costs of $300 million (8.7% saving). An intervention of this efficacy costing anything up to $1400 is likely to be cost-effective in this setting.Conclusions. Interventions aimed at curing HIV infection have the potential to improve overall disease burden and to reduce costs. Given the effectiveness and cost of ART, such interventions would have to be inexpensive and highly effective.

ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions.

The recently completed HIV prevention trials network study 052 is a landmark collaboration demonstrating that HIV transmission in discordant couples can be dramatically reduced by treating the infected individual with antiretroviral therapy (ART). However, the cellular and virological events that occur in the female reproductive tract (FRT) during ART that result in such a drastic decrease in transmission were not studied and remain unknown. Here, we implemented an in vivo model of ART in BM/liver/thymus (BLT) humanized mice in order to better understand the ability of ART to prevent secondary HIV transmission. We demonstrated that the entire FRT of BLT mice is reconstituted with human CD4+ cells that are shed into cervicovaginal secretions (CVS). A high percentage of the CD4+ T cells in the FRT and CVS expressed CCR5 and therefore are potential HIV target cells. Infection with HIV increased the numbers of CD4+ and CD8+ T cells in CVS of BLT mice. Furthermore, HIV was present in CVS during infection. Finally, we evaluated the effect of ART on HIV levels in the FRT and CVS and demonstrated that ART can efficiently suppress cell-free HIV-RNA in CVS, despite residual levels of HIV-RNA+ cells in both the FRT and CVS.