Antiretroviral Therapy Eligibility Research Articles

Utilizing local likelihood in regression discontinuity design: Investigating the impact of antiretroviral therapy eligibility on retention in clinical HIV care in South Africa.

The regression discontinuity (RD) design is a widely utilized approach for assessing treatment effects. It involves assigning treatment based on the value of an observed covariate in relation to a fixed threshold. Although the RD design has been widely employed across various problems, its application to specific data types has received limited attention. For instance, there has been little research on utilizing the RD design when the outcome variable exhibits zero-inflation. This study introduces a novel RD estimator using local likelihood, which overcomes the limitations of the local linear regression model, a popular approach for estimating treatment effects in RD design, by considering the data type of the outcome variable. To determine the optimal bandwidth, we propose a modified Ludwig-Miller cross validation method. A set of simulations is carried out, involving binary, count, and zero-inflated outcome variables, to showcase the superior performance of the suggested method over local linear regression models. Subsequently, the proposed local likelihood model is employed on HIV care data, where antiretroviral therapy eligibility is determined by a CD4 count threshold. A comparison is made between the results obtained using the local likelihood model and those obtained using local linear regression.

Incident Kaposi sarcoma during the expansion of antiretroviral therapy eligibility in Nigeria: a retrospective cohort study

IntroductionThe expansion of antiretroviral therapy (ART) eligibility could lead to earlier initiation of Human Immunodeficiency Virus (HIV) treatment and consequently reduce the risk of HIV-associated Kaposi Sarcoma (KS). We investigated the impact of changes in the Nigerian HIV treatment guidelines on KS incidence among adults enrolled in HIV care in Nigeria.MethodsWe analyzed data of adults who enrolled for HIV care from January 2006 to December 2016 at one of Nigeria’s largest HIV treatment centers. Based on changes in HIV treatment guidelines, we classified 2006–2009 as the pre-expansion period and 2010–2016 as the post-expansion period. We used Kaplan Meier curves to compare the incidence of KS in the pre-expansion to the post-expansion period. We used Cox regression models to assess the hazard for incident KS between the two periods after adjusting for potential confounders.ResultsAmong 14,479 patients with HIV, the overall KS incidence was 2.35; 95% CI 2.01–2.74/1,000 person-years. The incidence of KS decreased from 2.53 to 1.58 per 1,000 person-years from 2006 to 2009 to 2010–2016. In models adjusting for age, sex, CD4-T cell count, and ART use, the risk for KS remained lower in 2010–2016 compared to 2006–2009. In analyses restricted to time on ART, there was no significant difference in KS incidence between HIV patients who enrolled in 2006–2009 and 2010–2016 after adjusting for age, sex, and CD4 T-cell count.ConclusionThe expansion of ART eligibility was associated with a reduced incidence of HIV-associated KS among adults initiating HIV care in Jos, Nigeria. The reduction was likely driven by earlier enrollment for HIV care and ART initiation.

Cost-outcome analysis of HIV testing and counseling, linkage, and defaulter tracing services in Bukoba, Tanzania

ABSTRACT Effective services along the HIV continuum of care from HIV testing and counseling to linkage, and from linkage to antiretroviral therapy (ART) initiation and retention, are key to improved health outcomes of persons living with HIV. A comprehensive analysis of the costs and outcomes of cascade services is needed to help allocate and prioritize resources to achieve UNAIDS targets. We evaluated the costs and population-level impact of a community-wide, integrated scale-up of testing, linkage, and defaulter-tracing programs implemented in Bukoba Municipal Council, Tanzania. Costs per identified HIV-positive client for provider-initiated, and home- and venue-based testing and counseling were $92.64 United States dollars (USD), $256.33 USD, and $281.57 USD, respectively. Costs per patient linked to HIV care and ART were $47.69 USD and $74.12 USD, respectively, during all ART-eligibility periods combined. Costs per defaulter traced and returned to HIV care were $47.56 USD and $206.77 USD, respectively. The provider-initiated testing and counseling was the most cost-effective modality. Testing approaches targeted to populations groups and geographic location with high testing positivity rates may improve the overall efficiency of testing services. The expansion of ART eligibility criteria and high linkage rate also result in efficiency gains and economies of scale of linkage services.

Implementing a Rapid Antiretroviral Therapy Program Using Starter Packs for Emergency Department Patients Diagnosed With HIV Infection.

Emergency departments (ED) have been identified as essential partners in the national plan to end the HIV epidemic. The initiation of rapid antiretroviral therapy (ART) may be an important strategy to minimize the treatment barriers faced by many ED patients diagnosed with HIV. We describe the implementation and outcomes of a protocol to provide rapid ART by using starter packs for eligible ED patients testing HIV antigen/antibody (Ag/Ab) reactive. Eligible patients were not pregnant, were unlikely to have a false-positive Ag/Ab test result, were discharged home, were ART naive, had acceptable liver and renal function, lacked symptoms of an opportunistic infection, and were judged to be a good candidate. During the 1-year study period, 10 606 HIV tests were performed, and 106 patients were HIV Ag/Ab reactive and assessed for ED rapid ART eligibility. Thirty-one patients (29.2%) were eligible for ED rapid ART; 26 (24.5%) were offered it; and 25 accepted and were provided starter packs for an overall ED rapid ART treatment rate of 23.6%. Two patients receiving ED rapid ART were confirmed to be HIV negative. Patients provided ED rapid ART were more likely to follow up by 30 days (82.6% vs 50.0%, P = .01) than patients not provided ED rapid ART. The 6-month incidence of immune reconstitution inflammatory syndrome was 4.3% among the 23 patients who were HIV positive and receiving ED rapid ART. The initiation of ED rapid ART for patients testing HIV Ag/Ab reactive is feasible, well accepted, and safe and may be an important facilitator of linkage to care.

Pediatric Antiretroviral Therapy Coverage and AIDS Deaths in the "Treat All" Era.

In 2015, CD4-based clinical staging criteria for antiretroviral therapy (ART) initiation were removed, expanding ART eligibility ("Treat All") for children, who shoulder an outsized burden of HIV-related deaths. To quantify the impact of "Treat All" on pediatric HIV outcomes, we examined shifts in pediatric ART coverage and AIDS mortality before and after "Treat All" implementation. We abstracted country-level ART coverage (proportion of children <15 years on ART) and AIDS mortality (deaths per 100 000 population) estimates over 11 years. For 91 countries, we also abstracted the year "Treat All" was incorporated into national guidelines. We used multivariable 2-way fixed effects negative binomial regression to estimate changes in pediatric ART coverage and AIDS mortality potentially attributable to "Treat All" expansion, reported as adjusted incidence rate ratios (adj.IRR) with 95% confidence intervals (95% CI). From 2010 to 2020, pediatric ART coverage tripled (16% to 54%), and AIDS-related deaths were halved (240 000 to 99 000). Compared with the pre-implementation period, observed ART coverage continued increasing after "Treat All" adoption, but this rate of increase declined by 6% (adj.IRR = 0.94, 95% CI: 0.91-0.98). AIDS mortality continued declining after "Treat All" adoption, but this rate of decline decreased by 8% (adj.IRR = 1.08, 95% CI: 1.05-1.11) in the post-implementation period. Although "Treat All" called for increased HIV treatment equity, ART coverage continues lagging in children and comprehensive approaches that address structural issues, including family-based services and intensified case-finding, are needed to close pediatric HIV treatment gaps.

A Sequential Multiple Assignment Randomized Trial of scalable interventions for ART delivery in South Africa: the SMART ART study

BackgroundOf the 8 million people in South Africa living with HIV, 74% of persons living with HIV are on antiretroviral therapy (ART) and 65% are virally suppressed. Detectable viral load results in HIV-associated morbidity and mortality and HIV transmission. Patient barriers to care, such as missed wages, transport costs, and long wait times for clinic visits and ART refills, are associated with detectable viral load. HIV differentiated service delivery (DSD) has simplified ART delivery for clients who achieve viral suppression and engage in care. However, DSD needs adaptation to serve clients who are not engaged in care.MethodsA Sequential Multiple Assignment Randomized Trial will be undertaken in KwaZulu-Natal, South Africa, to test adaptive ART delivery for persons with detectable viral load and/or who are not engaged in care. The types of differentiated service delivery (DSD) which will be examined in this study are clinic-based incentives, community-based smart lockers, and home delivery. The study plans to enroll up to 900 participants-people living with HIV, eligible for ART, and who are not engaged in care. The study aims to assess the proportion of ART-eligible persons living with HIV who achieve viral suppression at 18 months. The study will also evaluate the preferences of clients and providers for differentiated service delivery and evaluate the cost-effectiveness of adaptive HIV treatment for those who are not engaged in care.DiscussionTo increase population-level viral suppression, persons with detectable viral load need responsive DSD interventions. A Sequential Multiple Assignment Randomized Trial (SMART) design facilitates the evaluation of a stepped, adaptive approach to achieving viral suppression with “right-sized” interventions for patients most in need of effective and efficient HIV care delivery strategies.Trial registrationClinicalTrials.gov NCT05090150. Registered on October 22, 2021

Projected outcomes of universal testing and treatment in a generalised HIV epidemic in Zambia and South Africa (the HPTN 071 [PopART] trial): a modelling study

The long-term impact of universal home-based testing and treatment as part of universal testing and treatment (UTT) on HIV incidence is unknown. We made projections using a detailed individual-based model of the effect of the intervention delivered in the HPTN 071 (PopART) cluster-randomised trial. In this modelling study, we fitted an individual-based model to the HIV epidemic and HIV care cascade in 21 high prevalence communities in Zambia and South Africa that were part of the PopART cluster-randomised trial (intervention period Nov 1, 2013, to Dec 31, 2017). The model represents coverage of home-based testing and counselling by age and sex, delivered as part of the trial, antiretroviral therapy (ART) uptake, and any changes in national guidelines on ART eligibility. In PopART, communities were randomly assigned to one of three arms: arm A received the full PopART intervention for all individuals who tested positive for HIV, arm B received the intervention with ART provided in accordance with national guidelines, and arm C received standard of care. We fitted the model to trial data twice using Approximate Bayesian Computation, once before data unblinding and then again after data unblinding. We compared projections of intervention impact with observed effects, and for four different scenarios of UTT up to Jan 1, 2030 in the study communities. Compared with standard of care, a 51% (95% credible interval 40-60) reduction in HIV incidence is projected if the trial intervention (arms A and B combined) is continued from 2020 to 2030, over and above a declining trend in HIV incidence under standard of care. A widespread and continued commitment to UTT via home-based testing and counselling can have a substantial effect on HIV incidence in high prevalence communities. National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill &amp; Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health.

Comparison of baseline lymphoma and HIV characteristics in Malawi before and after implementation of universal antiretroviral therapy.

Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016-2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting. Trial registration: ClinicalTrials.gov identifier: NCT02835911.

Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016-2019.

Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The "Treat all" strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 -December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30-45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8-51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21-2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51-3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35-44 (aHR 0.65, 95%CI: 0.44-0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39-0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53-3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75-3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57-6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51-0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20-0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects-average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06-1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11-2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01-0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004-0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes.

Perspectives on preparing for long-acting injectable treatment for HIV among consumer, clinical and nonclinical stakeholders: A qualitative study exploring the anticipated challenges and opportunities for implementation in Los Angeles County.

Long-acting injectable (LAI) antiretroviral therapy (ART) is a novel HIV treatment option for people with HIV. The first LAI ART regimen for HIV treatment received regulatory approval in the United States in January 2021. In February 2020, we collected qualitative data from 18 consumers and 23 clinical and non-clinical stakeholders to catalog anticipated individual-consumer, healthcare system, and structural levels barriers and facilitators to LAI ART implementation in Los Angeles County, California. Thematic analysis was guided by the CFIR implementation science model. CFIR constructs of intervention characteristics, individual characteristics, outer and inner setting, intervention characteristics, and implementation process emerged in analysis. Under intervention characteristics, anticipated facilitators included the relative advantage of LAI ART over pills for adherence and reduced treatment management burden and related anxiety; anticipated barriers included non-adherence to injection appointments, concerns of developing HIV resistance, discomfort with injection and cost. Anticipated facilitators based on individual characteristics included overall acceptability based on knowledge and positive beliefs about LAI ART. Participant noted several characteristics of the outer setting that could negatively impact implementation, such as medical mistrust, external policies, and LAI ART eligibility (i.e., to be virally suppressed prior to initiation). Participants were optimistic about the potential to decrease stigma but expressed that provider willingness for adoption could be hindered by challenges in organizational inner setting related to payment authorizations, increased staffing needs, medication procurement and storage, and provider and healthcare system readiness. Results from this pre-implementation study may inform rollout and scale-up of LAI ART in Los Angeles County.

Clinical Characteristics of Incident Lymphoma in Malawi before and after Implementation of Universal Anti-Retroviral Therapy

Purpose:In 2016, Malawi implemented a universal test and treat (UTT) policy, expanding eligibility for antiretroviral therapy (ART) to anyone with confirmed HIV infection. Prior to 2016, Malawi restricted ART initiation to HIV-positive individuals with CD4 count ≤500 cells/µL, with WHO staging ≥III who were pregnant or breastfeeding, or who were younger than 5 years old. Here, we assess the impact on distribution of lymphoma presentation and baseline clinical characteristics at Kamuzu Central Hospital, Lilongwe, Malawi.Methods:Participants with newly diagnosed, pathologically confirmed lymphoproliferative disorders were enrolled from 2013 - 2020. We categorized participants as pre-universal ART (pre-UART) if enrolled during 2013-June 2016 or post-universal ART (post-UART) if enrolled during July 2016-2020 and evaluated clinical characteristics.Findings:Of 412 total participants, 156 were pre-UART and 256 were post-UART. The most common diagnoses were diffuse large B-cell lymphoma (DLBCL) (45%), low-grade lymphoma (11%), Burkitt lymphoma (10%), Hodgkin lymphoma (9%), and multicentric Castleman disease (7%) and there was no significant difference in distribution of diagnoses between pre-UART and post-UART periods (Figure 1). HIV prevalence was 50%, mean age 43, and 62% male. Sixty-six percent (48/73) of pre-UART HIV-positive participants knew their HIV status, for median 5 years (IQR 2-8) and 71% (41/58) were on ART for median 4 years (IQR 2-7). Eighty percent (94/117) of post-UART HIV positive participants knew their HIV status (p=0.02), for median 4 years (IQR 2-9) and 84% (89/106) were on ART (p=0.05) for median 4 years (IQR 2-8). HIV was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p=0.05). Among DLBCL participants, 61% (23/38) of pre-UART HIV-positive participants knew their HIV status, for median 5 years (IQR 2-9), 61% (19/31) were on ART for median 4 years (IQR 2-6). Eighty-two percent (n=51/63) of post-UART DLBCL HIV-positive participants knew their HIV status (p=0.02) for median 5 years (IQR 2-9) and 89% (47/53) were on ART (p < 0.01) for median 5 years (IQR 2-9). Post-UART DLBCL participants had median HIV viral load of 0 log copies/mL (IQR 0-10) compared to pre-UART (6.2; IQR 0-10) (p=0.09). CD4 count, age adjusted-IPI and Ki67 proliferation index were similar for DLBCL patients in the two groups.Interpretation:There were no significant differences in lymphoma subtypes diagnosed or in traditional DLBCL prognostic factors after implementation of universal ART in Malawi. However, HIV was better controlled in the post-UART period and differences in immunological status may have implications for therapy and prognosis. Strengths of this study include a deeply characterized cohort, both clinically and pathologically. As opposed to epidemiological data from the US and Europe, we did not see a major shift in diagnoses over this time period with increasing access to ART. However, possible explanations for the differences include that this is not a epidemiological survey as cancer registration data is not comprehensively collected in Malawi and that the roll out of ART across sub-Saharan Africa has been much more gradual than the abrupt increase in access that was seen in the US and Europe. Therefore, epidemiological chances may also be more gradual. In summary, this is some of the most comprehensive data on lymphoma presentation from sub-Saharan Africa across periods of increasing access to ART and despite improved HIV control among incident lymphoma cases, there was no change in the distribution of diagnoses in this time period. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Understanding Repeat Positive HIV Testing in South Africa Under Changing Treatment Guidelines.

Some people with HIV (PWH) test positive multiple times without initiating antiretroviral therapy (ART). We surveyed 496 ART-eligible PWH following routine HIV testing at three clinics in Soweto and Gugulethu, South Africa in 2014-2015. Among repeat positive testers (RPTs) in this cohort, we compared rates of treatment initiation by prior treatment eligibility and assessed psychosocial predictors of treatment initiation in logistic regression models. RPTs represented 33.8% of PWH in this cohort. Less than half of those who reported eligibility for ART on prior testing started treatment upon retesting, in contrast to two thirds of RPTs who were previously ineligible for treatment who started treatment once they learned of their eligibility. Those who reported coping through substance use were more likely to decline treatment versus those not using substances. PWH who test repeatedly represent a vulnerable population at risk for ART non-initiation who may benefit from interventions addressing individualized coping strategies.

Differentiated service delivery for people using second-line antiretroviral therapy: clinical outcomes from a retrospective cohort study in KwaZulu-Natal, South Africa.

IntroductionEvidence is needed to guide the inclusion of broader groups of people living with HIV (PLHIV) in differentiated service delivery (DSD) programmes. We assessed treatment outcomes among PLHIV on second‐line regimens in a community antiretroviral therapy (ART) delivery programme, compared to those who remained at clinics.MethodsUsing data from 61 public clinics, we did a retrospective cohort study among PLHIV receiving second‐line ART following rollout of the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme in KwaZulu‐Natal, South Africa. We included PLHIV from the timepoint when they were first eligible, though not necessarily referred, for community ART within CCMDD and followed them for 18 months. We used multivariable logistic regression to compare 12‐month attrition and viraemia between clients referred for community ART and those remaining in clinic care.ResultsAmong 209,744 PLHIV aged ≥ 18 years who collected ART between October 2016 and December 2018, 7511 (3.6%) received second‐line ART. Of these, 2575 (34.3%) were eligible for community ART. The median age was 39.0 years (interquartile range 34.0–45.0) and 1670 (64.9%) were women. Five hundred and eighty‐four (22.7%) were referred for community ART within 6 months of meeting eligibility criteria. Overall, 4.5% [95% confidence interval (CI) 3.0–6.6%] in community ART and 4.4% (95% CI 3.5–5.4%) in clinic care experienced attrition at 12 months post eligibility for community ART. Two thousand one hundred and thirty‐eight (83.0%) had a viral load recorded 6–18 months after becoming eligible, and of these, 10.3% (95% CI 7.7–13.3%) in community ART and 11.3% (95% CI 9.8–12.9%) in clinic care had viraemia > 200 copies/ml. In separate regressions adjusted for age, gender, district, time on second‐line ART, nucleoside reverse transcriptase inhibitor backbone and year of eligibility, no differences in the odds of attrition [adjusted odds ratio (aOR) 1.02, 95% CI 0.71–1.47] or viraemia (aOR 0.91, 95% CI 0.64–1.29) were observed between those in community ART and those remaining in clinic care.ConclusionsWe found good outcomes among PLHIV who were stable on second‐line regimens and referred for community ART. Efforts to expand DSD access among this group should be prioritized.

Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries

ObjectiveTo determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. Study Design and SettingWe used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. ResultsWe found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). ConclusionTreat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Predicting HIV Incidence in the SEARCH Trial: A Mathematical Modeling Study.

The SEARCH study provided community-based HIV and multidisease testing and antiretroviral therapy (ART) to 32 communities in East Africa and reported no statistically significant difference in 3-year HIV incidence. We used mathematical modeling to estimate the effect of control arm viral suppression and community mixing on SEARCH trial outcomes. Uganda and Kenya. Using the individual-based HIV modeling software EMOD-HIV, we configured a new model of SEARCH communities. The model was parameterized using demographic, HIV prevalence, male circumcision, and viral suppression data and calibrated to HIV prevalence, ART coverage, and population size. Using assumptions about ART scale-up in the control arm, degree of community mixing, and effect of baseline testing, we estimated comparative HIV incidence under multiple scenarios. Before the trial results, we predicted that SEARCH would report a 4%-40% reduction between arms, depending on control arm ART linkage rates and community mixing. With universal baseline testing followed by rapidly expanded ART eligibility and uptake, modeled effect sizes were smaller than the study was powered to detect. Using interim viral suppression data, we estimated 3-year cumulative incidence would have been reduced by up to 27% in the control arm and 43% in the intervention arm compared with a counterfactual without universal baseline testing. Our model suggests that the active control arm substantially reduced expected effect size and power of the SEARCH study. However, compared with a counterfactual "true control" without increased ART linkage because of baseline testing, SEARCH reduced HIV incidence by up to 43%.

The effect of eligibility for antiretroviral therapy on body mass index and blood pressure in KwaZulu-Natal, South Africa

We use a regression discontinuity design to estimate the causal effect of antiretroviral therapy (ART) eligibility according to national treatment guidelines of South Africa on two risk factors for cardiovascular disease, body mass index (BMI) and blood pressure. We combine survey data collected in 2010 in KwaZulu-Natal, South Africa, with clinical data on ART. We find that early ART eligibility significantly reduces systolic and diastolic blood pressure. We do not find any significant effects on BMI. The effect on blood pressure can be detected up to three years after becoming eligible for ART.

Abstract 88: Clinical Characteristics of Incident Lymphoma in Malawi before and after Implementation of Universal ART

Abstract Purpose: In 2016, Malawi expanded eligibility for antiretroviral therapy (ART) to anyone with confirmed HIV infection. Here, we assess the impact on lymphoma presentation. Methods: We enrolled patients with newly diagnosed lymphoproliferative disorders 2013-2020. We categorized patients pre-universal ART (pre-UART) (2013-June 2016) or post-universal ART (post-UART) (July 2016-2020) and evaluated clinical characteristics. Results: There were 157 cases pre-UART and 256 post-UART. The most common diagnoses were diffuse large B-cell lymphoma (DLBCL) (43%), low-grade lymphoma (12%), Burkitt lymphoma (10%), Hodgkin lymphoma (9%), and multicentric Castleman disease (7%). HIV prevalence was 50%, mean age 43, and 62% male. 66% of pre-UART HIV+ knew their HIV status, for median 5 years (IQR 2-8), and 53% were on ART for median 4 years (IQR 2-7). 80% of post-UART HIV+ knew their HIV status (p=0.02), for median 4 years (IQR 2-9) and 70% were on ART for median 4 years (IQR 2-8). HIV was suppressed &amp;lt;1000 copies/mL in 56% (n=33/59) pre-UART and 71% (n=73/103) post-UART (p=0.05). Among DLBCL, 61% (n=23/38) of pre-UART HIV+ knew their HIV status, for median 5 years (IQR 2-9), and 46% were on ART for median 4 years (IQR 2-6). 82% (n=51/62) of post-UART DLBCL HIV+ knew their HIV status (p=0.02), for median 5 years (IQR 2-9) and 68% were on ART for median 5 years (IQR 2-9). Post-UART DLBCL patients had median HIV viral load of 0 log copies/mL (IQR 0-10) compared to pre-UART (6.2 log copies/mL, IQR 0-10) (p=0.09). CD4 count, age adjusted-IPI and Ki67 proliferation index were similar between DLBCL in the two groups. Conclusion: There were no significant differences in lymphoma subtypes diagnosed or in traditional DLBCL prognostic factors after implementation of universal ART in Malawi. However, HIV was better controlled in the post-UART period and differences in immunological status may have implications for therapy and prognosis. Citation Format: Yolanda Gondwe, Evaristar Kudowa, Matthew Painschab, Tamiwe Tomoka, Yuri Fedoriw, Edwards Kasonkanji, Bongani Kaimila, Takondwa Zuze, Victor Mithi, Noel Mumba, Stephen Kimani, Maurice Mulenga. Clinical Characteristics of Incident Lymphoma in Malawi before and after Implementation of Universal ART [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 88.

The Impact of Immediate Initiation\xa0of\xa0Antiretroviral Therapy on Patients' Healthcare Expenditures: A Stepped-Wedge Randomized Trial in Eswatini

Immediate initiation of antiretroviral therapy (ART) for all people living with HIV has important health benefits but implications for the economic aspects of patients' lives are still largely unknown. This stepped-wedge cluster-randomized controlled trial aimed to determine the causal impact of immediate ART initiation on patients’ healthcare expenditures in Eswatini. Fourteen healthcare facilities were randomly assigned to transition at one of seven time points from the standard of care (ART eligibility below a CD4 count threshold) to the immediate ART for all intervention (EAAA). 2261 patients living with HIV were interviewed over the study period to capture their past-year out-of-pocket healthcare expenditures. In mixed-effects regression models, we found a 49% decrease (RR 0.51, 95% CI 0.36, 0.72, p < 0.001) in past-year total healthcare expenditures in the EAAA group compared to the standard of care, and a 98% (RR 0.02, 95% CI 0.00, 0.02, p < 0.001) decrease in spending on private and traditional healthcare. Despite a higher frequency of HIV care visits for newly initiated ART patients, immediate ART initiation appears to have lowered patients’ healthcare expenditures because they sought less care from alternative healthcare providers. This study adds an important economic argument to the World Health Organization’s recommendation to abolish CD4-count-based eligibility thresholds for ART.

Impact of immediate initiation of antiretroviral therapy among men who have sex with men infected with HIV in Chengdu, southwest China: trends analysis, 2008\u20132018

BackgroundGiven the rampant HIV epidemic among men who have sex with men (MSM) in Chengdu, southwest China, Treat All policy, defined as immediate antiretroviral therapy (ART) initiation after HIV diagnosis, was implemented since 2014. Real-world research evaluating impacts of immediate ART on HIV epidemics is needed to optimize policy-making as national and international guidelines have been lowering ART eligibility threshold. The purpose of this study is to: assess temporal trends of the HIV epidemic and impacts of Treat All policy among MSM; and lay foundation for HIV-related policy evaluation using longitudinal routine data from health information systems.MethodsData used in this study were HIV sentinel seroprevalence, annual reported HIV cases and ART coverage rate among MSM in Chengdu from 2008 to 2018, derived from national HIV/AIDS information system. Temporal trends of the HIV epidemic were described using Joinpoint Regression Program. Interrupted time-series method was deployed to evaluate Treat All policy.ResultsHIV sentinel seroprevalence rose from 11.20% in 2008 to 17.67% in 2013 and Annual Percent Change (APC) was 8.25% (95% CI − 2.40%, 20.07%), then decreased to 5.17% in 2018 (APC = − 19.63%, 95% CI − 27.54%, − 10.86%). Newly reported HIV cases increased from 168 cases in 2008 to 1232 cases in 2015 (APC = 26.99%, 95% CI 21.32%, 32.93%), and reduced to 1014 cases in 2018 (APC = − 8.80%, 95% CI − 18.45%, 2.01%). ART coverage rate has been climbing from 11.11% in 2008 to 92.29% in 2018 and Average Annual Percent Change was 16.09% (95% CI 11.76%, 20.59%). Results of interrupted time-series models showed that compared to an annual increase of 0.87% during pre-policy period, there was a decline of 3.08% (95% CI − 0.0366%, − 0.0250%) per year of HIV sentinel seroprevalence since 2014; and compared to an annual increase of 116 cases before 2014, there was an annual drop of 158 newly reported HIV cases (95% CI − 194.87%, − 121.69%) during the post-policy period.ConclusionsImmediate ART after HIV diagnosis could potentially curb HIV transmission at population level among MSM, along with other strategies. Future assessment of HIV prevention and control policy can be carried out using routinely collected longitudinal data from health information systems.

SEARCH Human Immunodeficiency Virus (HIV) Streamlined Treatment Intervention Reduces Mortality at a Population Level in Men With Low CD4 Counts.

We tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing. In the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk. Among 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P < .001). Mortality was reduced substantially more among men (RR = 0.61; 95% CI: .43, .86; P = .01) than among women (RR = 0.90; 95% CI: .62, 1.32; P = .58). After population-based HIV testing, streamlined care reduced population-level mortality among persons with HIV and CD4 ≤ 350/uL, particularly among men. Streamlined HIV care models may play a key role in global efforts to reduce AIDS deaths.