Delayed Antiretroviral Therapy Initiation Research Articles

Characterization of HIV-1 Reservoirs in Children and Adolescents: A Systematic Review and Meta-Analysis Toward Pediatric HIV Cure

ObjectiveTo conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally-acquired HIV infection. Study designRandomized and non-randomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRM) and the size of reservoirs were evaluated. Subgroup analyses were performed to characterize further the data, and the meta-analysis was done through random effect models. ResultsOverall, 49 studies from 17 countries worldwide were included, encompassing 2356 perinatally infected participants (48.83% females). There are limited data on the quantitative characterization of viral reservoirs in sub-Saharan Africa (SSA), with sensitive methodologies such as ddPCR rarely employed. The overall prevalence of ADRMs was 37.80% [95%CI: 13.89–65.17], with 48.79% [95%CI: 0–100] in Africa, 42.08% [6.68-82.71] in America, 23.88% [95%CI: 14.34–34.90] in Asia, and 20.00% [95%CI: 10.72–31.17] in Europe, without any difference between infants and adolescents (p=0.656). Starting antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (p=0.054). Participants with long suppressed viremia (>5 years) had lower levels of HIV-1 DNA (p=0.027). Ppre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with higher levels of HIV-1 DNA (p=0.038, p=0.047 and p=0.041, respectively). ConclusionThe pooled prevalence of ADRMs is high in perinatally infected pediatric population, with larger proviral reservoir size driven by delayed ART initiation, a shorter period of viral suppression, and immuno-virological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.

Impact of social determinants of health on time to antiretroviral therapy initiation and HIV viral undetectability for migrants enrolled in a multidisciplinary HIV clinic with rapid, free, and onsite B/F/TAF: 'The ASAP study'.

Multidisciplinary care with free, rapid, and on-site bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) dispensation may improve health outcomes among migrants living with HIV. However, models for rapid B/F/TAF initiation are not well studied among migrants living with HIV, and an understanding of how social determinants of health (SDH) may affect HIV-related health outcomes for migrants enrolled in such care models is limited. Within a 96-week pilot feasibility prospective cohort study at a multidisciplinary HIV clinic, participants received free B/F/TAF rapidly after care linkage. The effects of SDH (i.e., birth region, sexual orientation, living status, education, employment, French proficiency, health coverage, use of a public health facility outside our clinic for free blood tests, and time in Canada) and other covariates (i.e., age, sex) on median time to antiretroviral therapy (ART) initiation and HIV viral undetectability from care linkage were calculated via survival analyses. Thirty-five migrants were enrolled in this study. Median time to ART initiation and HIV undetectability was 5 days (range 0-50) and 57 days (range 5-365), respectively. Those who took significantly longer to initiate ART were aged <35 years, identified as heterosexual, had less than university-level education, or were unemployed. No factor was found to significantly affect time to undetectability. Despite the provision of free B/F/TAF, several SDH were linked to delays in ART initiation. However, once initiated and engaged, migrants living with HIV reached HIV undetectability efficiently. Findings provide preliminary support for adopting this care model with migrants living with HIV and suggest that SDH should be considered when designing clinical interventions for more equitable outcomes.

Identifying longitudinal patterns of HIV treatment (dis)engagement and re-engagement from oral histories of virologically unsuppressed persons in Uganda: A thematic trajectory analysis

BackgroundThere is limited study of persons deemed “harder to reach” by HIV treatment services, including those discontinuing or never initiating antiretroviral therapy (ART). We conducted narrative research in southern Uganda with virologically unsuppressed persons identified through population-based sampling to discern longitudinal patterns in HIV service engagement and identify factors shaping treatment persistence. MethodsIn mid-2022, we sampled adult participants with high-level HIV viremia (≥1000 RNA copies/mL) from the prospective, population-based Rakai Community Cohort Study. Using life history calendars, we conducted initial and follow-up in-depth interviews to elicit oral histories of participants’ journeys in HIV care, from diagnosis to the present. We then used thematic trajectory analysis to identify discrete archetypes of HIV treatment engagement by “re-storying” participant narratives and visualizing HIV treatment timelines derived from interviews and abstracted clinical data. ResultsThirty-eight participants (median age: 34 years, 68% men) completed 75 interviews. We identified six HIV care engagement archetypes from narrative timelines: (1) delayed ART initiation, (2) early treatment discontinuation, (3) treatment cycling, (4) prolonged treatment interruption, (5) transfer-related care disruption, and (6) episodic viremia. Patterns of service (dis)engagement were highly gendered, occurred in the presence and absence of optimal ART adherence, and were shaped by various factors emerging at different time points, including: denial of HIV serostatus and disclosure concerns; worsening HIV-related symptoms; psychological distress and depression; social support; intimate partner violence; ART side effects; accessibility constraints during periods of mobility; incarceration; and inflexible ART dispensing regulations. ConclusionsIdentified trajectories uncovered heterogeneities in both the timing and drivers of ART (re-)initiation and (dis)continuity, demonstrating the distinct characteristics and needs of people with different patterns of HIV treatment engagement throughout the life course. Enhanced mental health service provision, expanded eligibility for differentiated service delivery models, and streamlined facility switching processes may facilitate timely (re-)engagement in HIV services.

Prevalence of delayed antiretroviral therapy initiation among people living with HIV: A systematic review and meta-analysis.

HIV continues to be a global challenge. Key recommendations for HIV prevention and treatment are presented on rapid antiretroviral therapy (ART) initiation. However, several studies showed a high prevalence of delayed ART initiation. The aim of this systematic review and meta-analysis was to assess the prevalence of delayed ART initiation among HIV-infected patients globally. This review summarised eligible studies conducted between January 2015 and August 2022 on the prevalence of delayed ART initiation in HIV-infected adults (age ≥ 15). Relevant studies were systematic searched through PubMed/Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases. Random-effects models were used to calculate pooled prevalence estimates. The heterogeneity was evaluated using Cochran's Q test and I2 statistics. Moreover, potential sources of heterogeneity were explored using univariate subgroup analysis. Data on the prevalence of delayed ART initiation was pooled across 29 studies involving 34,937 participants from 15 countries. The overall pooled prevalence of delayed ART initiation was 36.1% [95% confidence interval (CI), 29.7-42.5%]. In subgroup analysis, the estimated pooled prevalence decreased with age. By sex, the prevalence was higher among male patients (39.3%, 95% CI: 32.2-46.4%) than female (36.5%, 95% CI: 26.9-50.7%). Patients with high CD4 cell count were more likely to delay ART initiation than those with low CD4 cell count (>500cells/mm3: 40.3%; 201-500cells/mm3: 33.4%; and ≤200cells/mm3: 25.3%). Our systematic review and meta-analysis identified a high prevalence of delayed ART initiation. The prolonged time interval between diagnosis and treatment is a prevalent and unaddressed problem that should spur initiatives from countries globally. Further research is urgently needed to identify effective strategies for promoting the early ART initiation.

Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

Timing of initiation of anti-retroviral therapy predicts post-treatment control of SIV replication.

One approach to 'functional cure' of HIV infection is to induce durable control of HIV replication after the interruption of antiretroviral therapy (ART). However, the major factors that determine the viral 'setpoint' level after treatment interruption are not well understood. Here we combine data on ART interruption following SIV infection for 124 total animals from 10 independent studies across 3 institutional cohorts to understand the dynamics and predictors of post-treatment viral control. We find that the timing of treatment initiation is an important determinant of both the peak and early setpoint viral levels after treatment interruption. During the first 3 weeks of infection, every day of delay in treatment initiation is associated with a 0.22 log10 copies/ml decrease in post-rebound peak and setpoint viral levels. However, delay in initiation of ART beyond 3 weeks of infection is associated with higher post-rebound setpoint viral levels. For animals treated beyond 3 weeks post-infection, viral load at ART initiation was the primary predictor of post-rebound setpoint viral levels. Potential alternative predictors of post-rebound setpoint viral loads including cell-associated DNA or RNA, time from treatment interruption to rebound, and pre-interruption CD8+ T cell responses were also examined in the studies where these data were available. This analysis suggests that optimal timing of treatment initiation may be an important determinant of post-treatment control of HIV.

Perspectives of people living with HIV on barriers to timely ART initiation following referral for antiretroviral therapy: A qualitative study at an urban HIV clinic in Kampala, Uganda.

Early initiation of antiretroviral therapy (ART) after HIV diagnosis prevents HIV transmission, progression of HIV to AIDS and improves quality of life. However, little is known about the barriers to timely ART initiation among patients who test HIV positive in settings different from where they will receive HIV treatment, hence are referred in the routine setting. Therefore, we explored the perspectives of people living with HIV on barriers faced to initiate ART following HIV testing and referral for treatment. In this qualitative study, we purposively sampled and enrolled 17 patients attending the Mulago ISS clinic. We selected patients (≥18 years) who previously were received as referrals for HIV treatment and had delayed ART initiation, as ascertained from their records. We conducted in-depth interviews, which were audio recorded, transcribed and translated. We used Atlas.ti version 9 software for data management. Data analysis followed thematic and framework analysis techniques and we adopted the socio-ecological model to categorize final themes. Key themes were found at organizational level including; negative experiences at the place of HIV diagnosis attributed to inadequate counselling and support, unclear communication of HIV-positive results and ambiguous referral procedures; and, long waiting time when patients reached the HIV clinic. At individual level, the themes identified were; immediate denial with late acceptance of HIV-positive results attributed to severe emotional and psychological distress at receiving results, fear of perceived side effects and long duration on ART. At interpersonal level, we found that anticipated and enacted stigma after HIV diagnosis resulted in non-disclosure, discrimination and lack of social support. We found that challenges at entry (during HIV test) and navigation of the HIV care system in addition to individual and interpersonal factors contributed to delayed ART initiation. Interventions during HIV testing would facilitate early ART initiation among patients referred for HIV care.

Factors Associated With Delayed and Late Initiation of Antiretroviral Therapy Among Patients With HIV in Beijing, China, 2010-2020.

Objectives: To determine factors associated with late and delayed antiretroviral therapy (ART) initiation in China and provide evidence for HIV prevention. Methods: Logistics regression model was used to determine factors associated with three outcomes: late (CD4 cell count <200cells/µL or clinical AIDS diagnosis prior to ART initiation), delayed (more than 1month between HIV diagnosis date and ART initiation) and either late or delayed ART initiation. Results: Multivariable analysis revealed that male, heterosexual, HIV diagnosis before 2014, HBV/HCV seropositive, and tuberculosis were associated with increased odds of all three outcomes. Conversely, married or cohabiting patients were less likely to have delayed ART initiation and either late or delayed ART initiation, while people who inject drugs were more likely to have these two outcomes. Additionally, older age was associated with an increased risk of having either late or delayed ART initiation, but a decreased risk of delayed ART initiation. Conclusion: The proportion of late and delayed ART initiation decreased significantly after the release of the 2016 guidelines in China. To further improve late diagnosis and early treatment, precise interventions for key populations are required.

Perceptions toward antiretroviral therapy and delayed ART initiation among people living with HIV in Changsha, China: mediating effects of treatment willingness.

Delayed antiretroviral therapy (ART) initiation is associated with poor HIV outcomes and a higher likelihood of HIV transmission. This cross-sectional study assessed the proportion of delayed ART initiation which was defined as initiating ART after 30 days of HIV diagnosis, and evaluated the pathways influencing ART initiation among adult PLWH in Changsha, China who were diagnosed between 2014 and 2022. Of 518 participants, 37.8% delayed in initiating ART. Based on the theory of reasoned action (TRA), delayed initiation was indirectly associated with perceptions toward ART through the mediating pathway of patients' treatment willingness, with treatment willingness significantly being the full mediator. The findings may guide the development of interventions to improve timely uptake of ART in people who are newly diagnosed with HIV.

Antiretroviral treatment interruption and resumption within 16 weeks among HIV-positive adults in Jinan, China: a retrospective cohort study.

Treatment interruption has been found to increase the risk of opportunistic infections and death among HIV-positive adults, posing a challenge to fully realizing antiretroviral therapy (ART). However, it has been observed that short-term interruption (<16 weeks) was not associated with significant increases in adverse clinical events. There remains a dearth of evidence concerning the interruption and resumption of ART after short-term discontinuation in China. HIV-positive adults who initiated ART in Jinan between 2004 and 2020 were included in this study. We defined ART interruption as more than 30 consecutive days off ART and used Cox regression to identify predictors of interruption. ART resumption was defined as a return to ART care within 16 weeks following discontinuation, and logistic regression was used to identify barriers. A total of 2,506 participants were eligible. Most of them were male [2,382 (95%)] and homosexual [2,109 (84%)], with a median age of 31 (IQR: 26-40) years old. Of all participants, 312 (12.5%) experienced a treatment interruption, and the incidence rate of interruption was 3.2 (95% CI: 2.8-3.6) per 100 person-years. A higher risk of discontinuation was observed among unemployed individuals [adjusted hazard ratio (aHR): 1.45, 95% CI: 1.14-1.85], with a lower education level (aHR: 1.39, 95% CI: 1.06-1.82), those with delayed ART initiation (aHR: 1.43, 95% CI: 1.10-1.85), receiving Alafenamide Fumarate Tablets at ART initiation (aHR: 5.19, 95% CI: 3.29-8.21). About half of the interrupters resumed ART within 16 weeks, and participants who delayed ART initiation, missed the last CD4 test before the interruption and received the "LPV/r+NRTIs" regimen before the interruption were more likely to discontinue treatment for the long term. Antiretroviral treatment interruption remains relatively prevalent among HIV-positive adults in Jinan, China, and assessing socioeconomic status at treatment initiation will help address this issue. While almost half of the interrupters returned to care within 16 weeks, further focused measures are necessary to reduce long-term interruptions and maximize the resumption of care as soon as possible to avoid adverse clinical events.

HIV Epidemiology, Care, and Treatment Outcomes Among Student and Nonstudent Youths Living With HIV in Southwest China Between 1996 and 2019: Historical Cohort Study.

Nearly one-third of new HIV infections occurred among youth in 2019 worldwide. Previous studies suggested that student youths living with HIV and nonstudent youths living with HIV might differ in some risk factors, transmission routes, HIV care, and disease outcomes. This study aimed to compare the HIV epidemic, disease outcomes, and access to care among student and nonstudent youths living with HIV aged 16 to 25 years in Guangxi, China. We performed a historical cohort study by extracting data on all HIV or AIDS cases aged 16 to 25 years in Guangxi, China, during 1996-2019 from the Chinese Comprehensive Response Information Management System of HIV or AIDS. We conducted analyses to assess possible differences in demographic and behavioral characteristics, HIV care, and disease outcomes between student and nonstudent youths living with HIV. Multivariate Cox regression was used to assess differences in mortality and virologic failure between student and nonstudent cases. A total of 13,839 youths aged 16 to 25 years were infected with HIV during 1996-2019. Among them, 10,202 cases were infected through sexual contact, most of whom were men (n=5507, 54%); 868 (8.5%) were students, and 9334 (91.5%) were not students. The number of student youths living with HIV was lower before 2006 but gradually increased from 2007 to 2019. In contrast, the nonstudent cases increased rapidly in 2005, then gradually declined after 2012. Student cases were mainly infected through homosexual contact (n=614, 70.7% vs n=1447, 15.5%; P<.001), while nonstudent cases were more likely to be infected through heterosexual contact (n=7887, 84.5% vs n=254, 29.3%; P<.001). Moreover, nonstudent cases had a significantly lower CD4 count than student cases at the time of HIV diagnosis (332 vs 362 cells/μL; P<.001). Nonstudents also had a delayed antiretroviral therapy (ART) initiation compared to students (93 days vs 22 days; P<.001). Furthermore, the mortality rate of 0.4 and 1.0 deaths per 100 person-years were recorded for student and nonstudent youths with HIV, respectively. Overall, the mortality risk in nonstudent cases was 2.3 times that of student cases (adjusted hazard ratio [AHR] 2.3, 95% CI 1.2-4.2; P=.008). The virologic failure rate was 2.3 and 2.6 per 100 person-years among student and nonstudent youths living with HIV, respectively. Nonstudent cases had double the risk of virologic failure compared to student cases (AHR 1.9, 95% CI 1.3-2.6; P<.001). Nonstudent youths living with HIV might face a low CD4 count at the time of HIV diagnosis, delayed ART initiation, and increased risk of death and virologic failure. Thus, HIV prevention and interventions should target youths who dropped out of school early to encourage safe sex and HIV screening, remove barriers to HIV care, and promote early ART initiation to curb the HIV epidemic among youths.

Predictors of delayed Anti-Retroviral Therapy initiation among adults referred for HIV treatment in Uganda: a cross-sectional study

BackgroundUganda’s current guidelines recommend immediate initiation of Anti-Retroviral Therapy (ART) for persons living with HIV in order to reduce HIV/AIDS related morbidity and mortality. However, not all eligible PLHIV initiate ART within the recommended time following HIV diagnosis. We assessed the prevalence and factors associated with delayed ART initiation among PLHIV referred for ART initiation, five years since rolling out the test and treat guidelines.MethodsIn this cross-sectional study, we enrolled adult patients referred to Mulago Immune Suppressive Syndrome (Mulago ISS) clinic for ART initiation from January 2017 to May 2021. We collected data on socio-demographics, HIV diagnosis and referral circumstances, and time to ART initiation using a questionnaire. The outcome of interest was proportion of patients that delayed ART, defined as spending more than 30 days from HIV diagnosis to ART initiation. We performed multivariable logistic regression and identified significant factors.ResultsA total of 312 patients were enrolled of which 62.2% were female. The median (inter-quartile range [IQR]) age and baseline CD4 count of the patients were 35 (28–42) years and 315 (118.8–580.5) cells/μL respectively. Forty-eight (15.4%) patients delayed ART initiation and had a median (IQR) time to ART of 92 (49.0–273.5) days. The factors associated with delayed ART initiation were; 1) having had the HIV diagnosis made from a private health facility versus public, (adjusted odds ratio [aOR] = 2.4 (95% confidence interval [CI] 1.1–5.5); 2) initial denial of positive HIV test results, aOR = 5.4 (95% CI: 2.0–15.0); and, 3) having not received a follow up phone call from the place of HIV diagnosis, aOR = 2.8 (95% CI: 1.2–6.8).ConclusionThere was significant delay of ART initiation among referred PLHIV within 5 years after the rollout of test and treat guidelines in Uganda. Health system challenges in the continuity of HIV care services negatively affects timely ART initiation among referred PLHIV in Uganda.

To explore patients’ perceptions about motivators and barriers of adherence to highly active antiretroviral therapy among people living with HIV: A qualitative study

ABSTRACT Objective: For people living with HIV (PLHIV), strict adherence to highly active antiretroviral therapy (HAART) is the key to effective treatment and retention in human immunodeficiency virus (HIV) care. There are many factors which promote or halt the antiretroviral therapy (ART) adherence practices. Therefore, the present study aimed to examine the HAART adherence levels and to explore patients’ views about barriers and facilitators to HIV treatment adherence. Methods: Semi-structured interviews were conducted among 15 PLHIV at the ART clinic of Dr. Ram Manohar Lohia Hospital, New Delhi. Interviews were audio-recorded in the local Hindi language, and bilingual experts (English and Hindi) transcribed verbatim. Qualitative data were coded for themes and subthemes and analyzed using a phenomenological approach as per thematic content analysis. Results: Feeling of hopelessness, delayed ART initiation, difficult initial phase of ART, forget to take ART on time, fear of disclosure of HIV diagnosis, lack of privacy and negative social support, and impact of lockdown due to COVID-19 were revealed as significant barriers to ART adherence. At the same time, commitment to raise and educate children, ART to increase life span, maintain oneself to be physically fit and healthy, only a single pill per day, very supportive counselors and health-care professionals, and hope to give birth to a healthy child were identified as facilitators of HIV retention. Conclusion: Understanding patient’s perception about ART adherence, its motivational and barrier factors which are directly affecting ART adherence and retention of PLHIV in HIV treatment and follow-ups are of utmost importance to improve ART adherence during HIV patient care services.

LB2305. Long Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection: Findings from the Extended Follow-up of the START Trial

Abstract Background Deferral of antiretroviral therapy (ART) initiation until CD4 count &amp;lt; 350 cells/μL in people with CD4 &amp;gt; 500 increases risk of AIDS and serious non-AIDS (SNA) conditions. Evidence from randomized trials is lacking to assess the extent to which ongoing excess risk due to having deferred initiation is reduced once ART is initiated and viral load suppressed. Methods START randomized 4684 ART-naïve HIV+ adults with CD4 &amp;gt; 500 cells/μL to start ART immediately (IMM, n=2325) or defer ART until CD4 &amp;lt; 350 cells/μL or AIDS developed (DEF, n= 2359). In 2015 the study demonstrated a 57% reduction in the risk of the primary endpoint (AIDS, SNA or death) for IMM ART; all assigned to DEF were recommended to start ART. Follow up continued to 31Dec2021. To determine whether the benefit of IMM compared to DEF was maintained, increased, or reduced, Cox models were used to estimate and compare hazard ratios (HR, IMM:DEF), for the primary endpoint and its components from randomization through 31Dec2015 (Pre 2016) with the period 1Jan2016 through 31Dec2021 (Post 2016). HRs for all follow-up, randomization through 31Dec2021, were also estimated. Results Pre 2016, median CD4 was 648 cells/μL in IMM and 460 cells/μL in DEF at ART initiation, a difference of 188 cells/μL (95% CI: 180-197); at the end of 2015, 98.9% of IMM and 84.8% of DEF were prescribed ART. The percentage of follow-up time spent on ART pre 2016 was 94.5% for IMM and 35.5% for DEF; and the average difference in CD4 count was 199 cells/μL. This contrasts with post 2016 during which the percentage of follow-up time on ART was 99.5% for IMM and 95.6% for DEF; and the average difference in CD4 was 155 cells/mL (Figure 1). During both time periods, initiation of ART led to rapid declines in HIV RNA to ≤ 200 copies/mL. For the primary endpoint and each component, the benefit of IMM compared to DEF in Post 2016 was reduced compared to Pre 2016 (Figure 2). Overall follow-up, from randomization to 2021 (median 9.3 years), the HR for the primary endpoint was 0.61 (95%CI: 0.49, 0.76; p&amp;lt; 0.001). Conclusion Among people with CD4 &amp;gt; 500, the excess risk of AIDS and SNA conditions associated with delaying ART initiation is substantially diminished soon after ART is initiated, but persistent excess risk remains. The results reinforce the importance of early diagnosis of HIV and prompt initiation of ART. Disclosures Gail Matthews, MBChB, PhD, Abbvie Inc: Grant/Research Support|Astra Zeneca: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support.

Simplified clinical algorithm for immediate antiretroviral therapy initiation: The HATI [HIV awal (early) Test & Treat in Indonesia] implementation research in Indonesia.

Although the World Health Organization recommends same day or rapid (< seven days) antiretroviral therapy (ART) initiation, delays in ART initiation remain common due to waiting for laboratory test results. This study employed a simplified clinical algorithm the HATI [HIV Awal (Early) Test & Treat Indonesia]-SAI (Simple ART Initiation) aimed to increase the proportion of ART uptake and decrease the time to ART initiation that can be used in various care settings. This study compared the percentage of ART uptake and retention, viral load (VL) suppression and time to ART initiation between the observation and intervention phases among newly diagnosed HIV patients from key populations. As part of the intervention, the newly diagnosed patients underwent screening using a simple form [consisting of data on age, height and weight (for body mass index calculation), questions on the presence of symptoms of HIV stages 1 and 2, tuberculosis, history of diabetes, hypertension and kidney disease], to determine eligibility for immediate ART initiation. Those who met the pre-defined criteria immediately received a combination of tenofovir lamivudine and efavirenz for two weeks. The baseline laboratory examination due to this was moved up to two weeks post ART. Factors significantly associated with ART uptake were also determined and their odds ratios were measured using logistic regression analysis. A total of 2173 people newly diagnosed with HIV were recruited, with 1579 and 594 in the observation and intervention phases, respectively. In both phases, the majority were men who have sex with men, who were young (<30 yr old) and employed, with high levels of education. The intervention phase significantly increased the proportion of ART initiation [91%, 95% confidence interval (CI): 89-93% vs. 78%, 95% CI: 76-80%] but did not have any impact on the proportion of six months retention and VL suppression. The intervention also significantly decreased the time to ART initiation from median ± interquartile range: 9±20 days to 2±10 days. The findings of this study suggest that the HATI-SAI intervention increased the uptake and decreased the time for immediate ART initiation. The HATI-SAI provides a simple and safe clinical approach that can readily be adopted in different settings without a costly investment in technology.

The contribution of late HIV diagnosis on the occurrence of HIV-associated tuberculosis.

To describe the timing of tuberculosis (TB) presentation in relation to diagnosis of HIV infection and antiretroviral therapy (ART) initiation and to evaluate whether the established impact from late presentation to care and late initiation of ART on the risk of TB is retained beyond the observation period of clinical trials. We used marginal structural models to emulate a clinical trial with up to 5 years of follow-up to evaluate the impact of late initiation on TB risk. People with HIV (PWH) were enrolled from 2007 to 2016 in observational cohorts from Uganda, Peru, Mexico and Italy. The risk of TB was compared in LP (accessing care with CD4 + cell count ≤350 cells/μl) vs. nonlate presentation using survival curves and a weighted Cox regression. We emulated two strategies: initiating ART with CD4 + cell count less than 350 cells/μl vs. CD4 + cell count at least 350 cells/μl (late initiation). We estimated TB attributable risk and population attributable fraction up to 5 years from the emulated date of randomization. Twenty thousand one hundred and twelve patients and 1936 TB cases were recorded. Over 50% of TB cases were diagnosed at presentation for HIV care. More than 50% of the incident cases of TB after ART initiation were attributable to late presentation; nearly 70% of TB cases during the first year of follow-up could be attributed to late presentation and more than 50%, 5 years after first attending HIV care. Late presentation accounted for a large share of TB cases. Delaying ART initiation was detrimental for incident TB rates, and the impact of late presentation persisted up to 5 years from HIV care entry.

Experiences of Antiretroviral Therapy Initiation Among HIV-Positive Adults in Ethiopia: A Descriptive Phenomenological Design.

PurposeThe aim of the study was to explore and describe the lived experiences of HIV-positive adults on antiretroviral therapy (ART) initiation in West Shoa Zone, Ethiopia.Materials and MethodsA descriptive phenomenological design was utilized in the study to gain insight into participants’ lived experiences regarding ART initiation in West Shoa Zone, Ethiopia. Data were collected through semi-structured in-depth interviews and analyzed by means of thematic analysis.ResultsThe study found that spousal influence, denial of status, inconsistent ART initiation protocol, poverty, fear of side effects, religion and shortages of staff were factors that caused delayed ART initiation. A low CD4 count, the development of opportunistic infections and the prevention of future illness were factors that promoted ART initiation.ConclusionThis study provides an overview of experiences of adults living with HIV regarding ART initiation. The study emphasizes the need to improve adequate provision of resources to address issues related to finance, human capital, guidelines and inequity to enhance early ART initiation among HIV-positive adults in West Shoa Zone. The study findings have implications for policy implementation, ART service delivery, and the enhancement of prompt ART initiation in the study settings.

‘I need time to start antiretroviral therapy’: understanding reasons for delayed ART initiation among people diagnosed with HIV in Lusaka, Zambia’

Introduction Rapid antiretroviral therapy (ART) initiation can improve patient outcomes such as viral suppression and prevent new infections. However, not everyone who can start ART does so immediately. Methods We conducted a qualitative study to inform interventions supporting rapid initiation in the ‘Test and Start’ era. We purposively sampled 20 adult patients living with HIV and a previous gap in care from ten health facilities in Lusaka, Zambia for interviews. We inductively analysed transcripts using a thematic, narrative approach. In their narratives, seven participants discussed delaying ART initiation. Results Drawing on messages gleaned from facility-based counselling and community information, many cited greater fear of rapid sickness or death due to imperfect adherence or treatment side effects than negative health consequences due to delayed initiation. Participants described needing time to ‘prepare’ their minds for a lifetime treatment commitment. Concerns about inadvertent HIV status disclosure during drug collection discouraged immediate initiation, as did feeling healthy, and worries about the impact of ART initiation on relationship dynamics. Conclusion Findings suggest that counselling messages should accurately communicate treatment risks, without perpetuating fear-based narratives about HIV. Identifying and managing patient-specific concerns and reasons for the ‘need for time’ may be important for supporting individuals to rapidly accept lifelong treatment. Key messages Fear-based adherence messaging in health facilities about the dangers of missing a treatment dose or changing the time when ART is taken contributes to Zambian patients’ refusals of immediate ART initiation Responsive health systems that balance a stated need for time to accept one's diagnosis and prepare to embark on a lifelong treatment plan with interventions to identify and manage patient-specific treatment related fears and concerns may support more rapid ART initiation Perceived social stigma around HIV continues to be a significant challenge for treatment initiation.

Pretreatment drug resistance in people living with HIV: A large retrospective cohort study in Chongqing, China.

ObjectivesThe emergence of pretreatment drug resistance (PDR) caused by increased usage of antiretroviral therapy (ART) represents a significant challenge to HIV management. In this study, we evaluated the prevalence of PDR in people living with HIV (PLWH) in Chongqing, China.MethodsWe retrospectively collected the data of 1110 ART‐naïve PLWH in Chongqing from January 1, 2018 to June 30, 2021. HIV‐1 genotypes and drug resistance were analyzed using the HIV‐1 pol sequence. Risk factors associated with PDR were evaluated via the logistic regression model.ResultsNine genotypes were detected among 1110 participants, with CRF07_BC (55.68%) being the dominant genotype, followed by CRF01_AE (21.44%), CRF08_BC (14.14%), and other genotypes (8.74%). Of all the participants, 24.14% exhibited drug resistance mutations (DRMs). The predominant DRMs for non‐nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were V179D/E/A/DIN (13.60%) and M184V/I (1.44%), respectively, whereas only two major DRMs (M46L and I54L) were identified for protease inhibitors (PIs). The total prevalence of PDR was 10.54%, with 2.43%, 7.66%, and 1.71% participants exhibiting PDR to NRTIs, NNRTIs, and PIs, respectively. Furthermore, female PLWH, delays in ART initiation, and the CRF08_BC genotype were associated with a higher risk of PDR.ConclusionsOur study provides the first large cohort data on the prevalence of PDR in Chongqing, China. HIV‐1 genotypes are diverse and complex, with a moderate level of PDR, which does not reach the threshold for the initiation of a public health response. Nevertheless, continuous surveillance of PDR is both useful and advisable.

Early Antiretroviral Therapy in AIDS Patients Presenting With Toxoplasma gondii Encephalitis Is Associated With More Sequelae but Not Increased Mortality.

BackgroundEvidence on the optimal time to initiate antiretroviral therapy (ART) in the presence of toxoplasmic encephalitis (TE) is scarce. We compared the impact of early vs. delayed ART initiation on mortality and neurologic complications at discharge in a Brazilian population co-infected with HIV and TE.MethodsWe retrospectively evaluated data from 9 years of hospitalizations at a referral center in Manaus, Amazonas. All ART-naïve hospitalized patients were divided into early initiation treatment (EIT) (0-4 weeks) and delayed initiation treatment (DIT) (>4 weeks). The groups were compared using chi-square test and mortality at 16 weeks.ResultsFour hundred sixty nine patients were included, of whom 357 (76.1%) belonged to the EIT group. The median CD4+ lymphocyte count and CD4+/CD8+ ratio were 53 cells/mm3 and 0.09, respectively. Mortality rate and presence of sequelae were 4.9% (n = 23) and 41.6% (n = 195), respectively. Mortality was similar between groups (p = 0.18), although the EIT group had the highest prevalence of sequelae at discharge (p = 0.04). The hazard ratio for death at 16 weeks with DIT was 2.3 (p = 0.18). The necessity for intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation were similar between groups.ConclusionIn patients with AIDS and TE, early ART initiation might have a detrimental influence on the occurrence of sequelae.