Early Mortality and Loss to Follow-up in HIV-Infected Children Starting Antiretroviral Therapy in Southern Africa

To the Editors: INTRODUCTION South Africa has the largest antiretroviral therapy (ART) program worldwide with 970,000 people receiving ART in 2009.1 As patient numbers have expanded, rising levels of loss to follow-up (LTFU) have significantly reduced the effectiveness of the national ART program, and increasing virological failure has become apparent.2,3 A causal association between increased facility patient caseload and worsening ART outcomes in South Africa is, however, not established.3 A recent study from Mozambique indicated increased attrition from clinics with high pharmacy staff burden.4 However, there is little other sub-Saharan data comparing ART outcomes between facilities with varying patient caseloads. This knowledge is valuable, as the most efficient approaches to further upscale treatment access while maintaining good ART outcomes are critical to the success of ART programs. To determine the effect of increasing facility patient burden on ART program effectiveness, this study compared program outcomes among 54 government primary health care ART facilities in 4 South African provinces. METHODS A multicohort study of adults enrolled at ART facilities supported by a nongovernmental organization (NGO) was conducted. The NGO provides clinical staff, infrastructure, clinical mentoring, community-based adherence support, and electronic data collection systems. Facilities are located in 4 provinces (Western Cape, KwaZulu-Natal, Eastern Cape, and Mpumalanga) in urban and rural areas. All ART-naive adults (16 years and older) enrolled on triple ART between January 2004 and September 2009, with documented date of birth, sex, date of starting ART, at least 1 day of follow-up, and who were enrolled at least 6 months before site database closure were included in the analyses. Patients were followed up until March 2010 or until the NGO exited from a site. Routine patient data were collected prospectively by facility-based data capturers at each clinic visit. Continual data cleaning and quality control routines were implemented to enhance data validity. Outcomes measures were death, LTFU, and virological suppression after starting ART. Attrition was defined as patient losses due to LTFU or death. LTFU was defined as no patient visit for 3 months or more beyond the last missed appointment. Viral load was measured 6 monthly on treatment, and virological suppression was defined as a viral load <400 copies per milliliter. The cumulative total of ART-naive adults enrolled at a facility at the end of the enrollment period was the measure of clinic patient load used. To guide the choice of how to categorize the sample according to facility load to optimize data fit, the Akaike information criterion from Cox models of facility load associated with outcomes was employed. A single cutoff of 950 patients was thus chosen, with facilities enrolling more than 950 patients classified as high caseload clinics and facilities enrolling fewer as low caseload clinics. Subgroup analyses were performed within high caseload clinic patients by comparing outcomes of patients enrolled prior to 6 months before enrollment of the 950th patient per site (the “early period” when the clinics had a low caseload) with patients enrolled thereafter (later period). Sensitivity analyses were conducted by modelling patient load alternatively as a 3-level ordinal variable, split at the tertiles of the sample distribution of cumulative facility enrollment (low tertile < 1067; mid tertile 1067-2031; high tertile > 2031 patients/facility, respectively). Kaplan-Meier estimates of outcomes were calculated. Time till initial virological suppression analyses were limited to patients having 1 or more viral load measurement within the first 12-month measurement period after starting ART. Multivariable Cox regression was used to estimate associations of patient and site-level factors with attrition and LTFU adjusting for baseline patient variables (age, sex, World Health Organization clinical stage, CD4 cell count, year of starting ART, tuberculosis treatment, pregnancy, and initial regimen) and site-related variables (province and rural/urban nature of site). Missing baseline values were classified as separate categories within variables,5 to retain observations in multivariable models. All adjusted models included all available baseline variables. All confidence intervals (CIs) quoted are 95% CIs. Statistical analyses were performed using Stata 11.1 (Stata Corporation, College Station, Texas). The study was approved by the University of Cape Town Research Ethics Committee. RESULTS Overall, 40,861 adults were included, of whom 11,830 (29.0%) were treated at 38 low caseload clinics and 29,031 (71.1%) were treated at 16 high caseload clinics. The median number enrolled per site was 488 [interquartile range (IQR): 291-736) and 2031 (IQR: 1275-3599) at low and high caseload clinics, respectively. The median age was 34.4 years (IQR: 29.3-41.1 years), being equivalent between groups (P = 0.26). Patients at high caseload facilities had a lower proportion of males (30.8% vs. 33.3%; P < 0.0005) and a lower median baseline CD4 cell count [117 cells/μL (IQR: 61-167) vs. 130 cells/μL (IQR: 71-177)]. Availability of baseline CD4 cell count results was 82.5%, with no difference between groups (P = 0.73). A higher proportion of patients were enrolled in earlier calendar years at high caseload facilities (44.5% enrolled pre-2008 vs. 23.7% at low caseload facilities, P < 0.0005). The duration of follow-up was 52,602 person-years. Cumulative LTFU was reduced at low caseload clinics, being 6.4% (CI: 5.9% to 7.0%) and 11.2% (CI: 10.4% to 12.2%) after 12 and 24 months of ART, respectively, vs. 8.6% (CI: 8.3% to 9.0%) and 14.9% (CI: 14.3% to 15.4%) at high caseload facilities, P < 0.0005 (Fig. 1). Mortality was equivalent between the groups, being 5.1% (CI: 4.9% to 5.4%) and 6.8% (CI: 6.5% to 7.1%), after 12 and 24 months overall, respectively (P = 0.40). After 36 months of ART, retention in care (1-attrition) remained superior at low caseload clinics, being 78.8% (CI: 76.7% to 80.8%) vs. 73.9% (CI: 73.1% to 74.7%), P < 0.0005.FIGURE 1: Cumulative probabilities of LTFU at low and high caseload clinics after starting ART. Low caseload clinics enrolled fewer than and high caseload clinics greater than 950 ART-naive adults onto ART.In adjusted multivariable analyses, high caseload clinics had independently increased probabilities of attrition and LTFU, adjusted hazard ratio (AHR) 1.26 (CI: 1.17 to 1.35; n = 40,861) and AHR 1.67 (CI: 1.52 to 1.83), respectively. Patients enrolled in later calendar years had independently increased risks of LTFU [AHR 2.25 (CI: 1.95 to 2.59), 2008-2009 vs. 2004-2005]. The subgroup of patients enrolled at high caseload clinics during the early period (during low caseload) totalled 9200 (31.7%) patients. This subgroup had independently better outcomes compared with patients enrolled during the later (high caseload) period; AHR of attrition and LTFU being 0.81 (CI: 0.75 to 0.88) and 0.74 (CI: 0.67 to 0.82), respectively. Mortality was equivalent, AHR 0.94 (CI: 0.82 to 1.09). In sensitivity analyses using the alternate exposure categorization, patients in the mid and high tertiles of facility caseload had independently increased attrition, AHR 1.20 (CI: 1.12 to 1.29) and AHR 1.37 (CI: 1.23 to 1.52), respectively. LTFU was increased, AHR 1.42 (CI: 1.29 to 1.55) and AHR 2.03 (CI: 1.77 to 2.33) in the mid and high tertiles, respectively. In both cases, a dose-response relationship was evident, with hazards of attrition and LTFU in the high tertile compared with the mid tertile being AHR 1.17 (CI: 1.05 to 1.31) and AHR 1.48 (CI: 1.29 to 1.70), respectively. Viral load result availability after 6 months of ART was better at low caseload clinics, being 61.1% vs. 58.4% (P < 0.0005). The proportion of patients achieving virological suppression at all time points on treatment was 87.2% (CI: 86.8% to 87.5%; n = 42,340), with no difference between groups (P = 0.30). The probability of achieving initial virologic suppression within 12 months of starting ART was, however, increased at low caseload clinics, being 88.3% (CI: 87.5% to 89.2%) vs. 85.0% (CI: 84.4% to 85.5%); P<0.0005, n = 22,251. [Low tertile 89.0% (CI: 88.2% to 89.7%), mid tertile 85.1% (CI: 84.3% to 86.0%), and high tertile 83.4% (CI: 82.5% to 84.3%); log rank trend P < 0.0005]. DISCUSSION Patients at facilities with larger patient loads had increased attrition due to LTFU and reduced initial virologic suppression in this multicohort study. Attrition increased, and initial virological suppression decreased in dose-dependent manners as facility patient loads expanded. LTFU increased in more recent years, similar to other South African cohorts.2,3,6 Low caseload clinics, however, had a decreased probability of LTFU despite having enrolled the majority of their patients in more recent years. Low ART health care provider to patient ratios have been associated with a reduced probability of starting ART after enrollment at HIV care facilities,7 and increased attrition with low pharmacy staff to patient ratios.4 However, no association between nonpharmacy health care provider to patient ratios and ART program attrition was evident in Uganda and Mozambique.4,8 Facility-level factors are nevertheless important determinants of ART outcomes.7 Large patient loads at facilities may overwhelm clinic administration systems and infrastructure, be associated with longer waiting times, and provide a higher caseload for community adherence support counsellors. Dissatisfaction with waiting times is an important predictor of discontent among ART patients.9 Strengths of this study include that a large number of patients from a broad range of sites and settings were analyzed, and individual-level data were collected prospectively, enabling adjustment of patient-level factors associated with outcomes. Limitations include that health care provider to patient ratios and facility infrastructure variables were not included in the analyses as data for all sites were unavailable. Attrition was raised at high caseload sites, although increased misclassification of patients as LTFU instead of deceased at high caseload sites might account for a degree of the raised LTFU observed. Facility patient burden may be assessed using alternate measures such as monthly visit count; cumulative patient enrollment is, however, a useful measure that is currently tracked in South African routine settings. In conclusion, these results further establish an association between increasing facility patient load and poorer ART outcomes. Further research should be conducted to elucidate underlying mechanisms explaining this and to identify potentially remedial interventions. ACKNOWLEDGMENTS The authors acknowledge Emmanuel Okoli, Kheth'Impilo colleagues, PEPFAR, Absolute Return for Kids, and the SA Health Department. Geoffrey Fatti, MBChB, MPH* Ashraf Grimwood, MBChB, MPH* Eula Mothibi, MBChB, FCP* Jawaya Shea, MHPE† *Kheth'Impilo, Cape Town, South Africa †Child Health Unit, School of Child & Adolescent Health, University of Cape Town, Cape Town, South Africa

BackgroundIn order to increase access to antiretroviral therapy (ART) in HIV-infected children, paediatric HIV care has been introduced in health centres in Ethiopia, where patients are managed by health professionals with limited training.ObjectiveTo compare outcomes of paediatric HIV care in hospital and health centre clinics and to determine risk factors for death and loss to follow-up (LTFU).DesignRetrospective comparison of patient characteristics and outcomes among children managed in a public hospital and all five public health centres in the uptake area.ResultsAmong 1,960 patients (health centres 572, hospital clinic 1,388), 34% were lost to follow-up, 2% died, 14% were transferred out, and 46% remained in care. Children initiating ART in the hospital clinic had lower median CD4 cell counts (age <1 year: 575 vs. 1,183 cells/mm3, p=0.024; age 1–5 years: 370 vs. 598 cells/mm3, p<0.001; age >5 years: 186 vs. 259 cells/mm3, p<0.001), and a higher proportion were <1 year of age (22% vs. 15%, p=0.025). ART initiation rates and retention in care were similar between children managed in health centres and in the hospital clinic (36% vs. 37% and 47% vs. 46%, respectively). Among patients starting ART, mortality was associated with age <1 year [hazard ratio (HR) 12.0; 95% confidence interval (CI): 3.5, 41]. LTFU was associated with CD4 cell counts <350 cells/mm3 (HR 1.8; 95% CI: 1.2, 3.0), weight-for-age z-scores below −4 (HR 2.8; 95% CI: 1.4, 5.6), and age <5 years (1–5 years: HR 1.6; 95% CI: 1.0, 2.5; <1 year: HR 3.3; 95% CI: 1.6, 6.6).ConclusionsOutcomes of HIV care were similar for Ethiopian children managed in a hospital clinic or in health centres. However, patients treated at the hospital clinic had characteristics of more advanced disease. Rates of LTFU were high in both types of health facility.

We explored the predictors and predictive models of loss to follow-up (LTFU) during the first year of anti-retroviral therapy (ART). LTFU was defined as the failure to visit the clinic for antiretroviral drugs for ≥ 90days after the last missed scheduled visit. Based on the electronic medical records of 5953 patients who were HIV positive and began ART between 2016 and 2019 in China, the LTFU rate was 7.24 (95% confidence interval 6.49-7.97) per 100 person-years during the first year of ART. ART baseline factors were associated with LTFU, but were non-optimal predictors. A model including ART process-related factors such as follow-up behaviors and physical health status had an area under the receiver operating characteristic curve of 73.4% for predicting LTFU. Therefore, the medical records of follow-up visits can be used to identify patients with a high risk of LTFU and allow interventions to be implemented proactively.

IntroductionEthiopia has recently adopted lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women (Option B+ strategy), regardless of CD4 count or clinical stage. However, the exact timing and predictors of loss to follow-up (LFU) are unknown. Thus, we examined the levels and determinants of LFU under Option B+ among pregnant and breastfeeding women initiated on lifelong ART for prevention of mother-to-child transmission (PMTCT) in Ethiopia.MethodsWe conducted a retrospective cohort study among 346 pregnant and breastfeeding women who started ART at 14 public health facilities in northeast Ethiopia from March 2013 to April 2015. We defined LFU as 90 days since the last clinic visit among those not known to have died or transferred out. We used Kaplan-Meier and Cox proportional hazards regression to estimate cumulative LFU and identify the predictors of LFU, respectively.ResultsOf the 346 women included, 88.4% were pregnant and the median follow-up was 13.7 months. Overall, 57 (16.5%) women were LFU. The cumulative proportions of LFU at 6, 12 and 24 months were 11.9, 15.7 and 22.6%, respectively. The risk of LFU was higher in younger women (adjusted hazard ratio (aHR) 18 to 24 years/30 to 40 years: 2.3; 95% confidence interval (CI): 1.2 to 4.5), in those attending hospitals compared to those attending health centres (aHR: 1.8; 95% CI: 1.1 to 3.2), in patients starting ART on the same day of diagnosis (aHR: 1.85; 95% CI: 1.1 to 3.2) and missing CD4 cell counts at ART initiation (aHR: 2.3; 95% CI: 1.2 to 4.4).ConclusionsThe level of LFU we found in this study is comparable with previous findings from other resource-limited settings. However, high early LFU shortly after ART initiation is still a major problem. LFU was high among younger women, those initiating ART on the day of HIV diagnosis, those missing baseline CD4 count and those attending hospitals. Thus, targeted HIV care and treatment programmes for these patients should be part of future interventions to improve retention in care under the Option B+ PMTCT programme.

BackgroundThis study aims to describe the trends in and determinants of six month mortality and loss to follow up (LTFU) during 2005–2009 in 13 outpatient clinics in Vietnam.MethodData were obtained from clinical records of 3,449 Vietnamese HIV/AIDS patients aged 18 years or older who initiated ART between 1 January 2005 and 31 December 2009. Mantel-Haenszel chi-square test, log rank test were conducted to examine the trends of baseline characteristics, six month mortality and LTFU. Cox proportional hazards regression models were performed to compute hazard ratio (HR) and 95% Confidence Interval (CI).ResultsThough there was a declining trend, the incidence of six month mortality and LTFU remained as high as 6% and 15%, respectively. Characteristics associated with six month mortality were gender (HR females versus males 0.54, 95%CI: 0.34–0.85), years of initiation (HR 2009 versus 2005 0.54, 95%CI: 0.41–0.80), low baseline CD4 (HR 350–500 cells/mm3 versus <50 cells/mm3 0.26, 95%CI: 0.18–0.52), low baseline BMI (one unit increase: HR 0.96, 95%CI: 0.94–0.97), co-infection with TB (HR 1.61, 95%CI: 1.46–1.95), history of injecting drugs (HR 1.58, 95%CI: 1.31–1.78). Characteristics associated with LTFU were younger age (one year younger: HR 0.97, 95%CI: 0.95–0.98), males (HR females versus males 0.82, 95%CI: 0.63–0.95), and poor adherence (HR 0.55, 95%CI: 0.13–0.87).ConclusionsTo reduce early mortality, special attention is required to ensure timely access to ART services, particularly for patients at higher risk. Patients at risk for LTFU after ART initiation should be targeted through enhancing treatment counselling and improving patient tracing system at ART clinics.

BackgroundLost to follow-up (LTFU) negatively affects the treatment success of Anti-Retroviral Therapy (ART) and thus, increases Tuberculosis-Human Immunodeficiency Virus (TB/HIV) related morbidity, mortality and hospitalization. However, the incidence and predictors of loss to follow up (LTFU) among adults with TB/HIV co-infection have not yet well-investigated in Ethiopia. Therefore, this study was aimed at investigating the incidence and predictors of LTFU in the study setting in particular.MethodsA facility based retrospective cohort study was employed among 305 (114 anemic and 191 normal) TB/HIV co-infected adults in two governmental hospitals (Mekelle Hospital and Ayder Comprehensive Specialized Hospital), Mekelle, Ethiopia from 2009 to 2016 and data were collected using checklist. Besides to descriptive statistics, a cox regression analysis was applied to identify statistically significant predictors of LTFU at 5% level of significance. Eventually, the Adjusted Hazard Ratio (AHR) and 95% Confidence Interval (CI) were estimated and interpreted for predictors of LTFU in the final cox model.ResultsGenerally, 45 of 305 (14.8%) of TB/HIV co-infected adults were LTFU with an incidence rate of 4.5 new LTFUs per 100 Person Years (PYs) and a median follow up time of 3.1 years (Interquartile Range (IQR): 0.8–5.3 Years). Hemoglobin level ≤ 11.0 g/dl (AHR = 2.660; 95%CI: 1.459–4.848), and any history of OI/s (AHR = 3.795; 95%CI: 1.165–12.364) were risk factors of LTFU. While, adverse drug events (AHR = 0.451; 95%CI: 0.216–0.941), TB treatment completion (AHR = 0.121; 95% CI: 0.057–0.254), and being on Isoniazid Preventive Therapy (IPT) (AHR = 0.085; 95%CI: 0.012–0.628) had protective effect against LTFU.ConclusionsOne in approximately seven TB/HIV co-infected adults had experienced of LTFU with an incidence rate 4.5 LTFUs per 100 PYs. The LTFU rate was higher among adults with low baseline hemoglobin level, no adverse drug events, presence of OI/s, failure to complete TB treatment, and being not on IPT. Therefore, it is advisable to treat anemia and active TB, and preventing the occurrence of OIs including TB using IPT to reduce the incidence of LTFU among TB/HIV co-infected adults.

HIV-infected children have less access to combination antiretroviral therapy as compared with adults in resource-limited settings. Growth faltering, loss to follow-up (LTFU) and high mortality are frequently seen. A retrospective cohort study was performed with parameters extracted from the Drug Resource Enhancement against AIDS and Malnutrition database for HIV-infected, antiretroviral naïve children under 15 years presenting for care at 17 Drug Resource Enhancement against AIDS and Malnutrition centers in Mozambique, Malawi and Guinea between January 2005 to December 2008. Predictors of time-to-death, time-to-LTFU and persistence of malnutrition by Cox's regression and Kaplan-Meier were determined. 2215 children presented to care with 1343 (61%) being ≤ 5 years. At baseline, stunting and malnutrition occurred in 40% and 25%, respectively; 75% of 2149 children had CD4 cell percentages less than 20; median HIV RNA, log10 cp/mL, was 4.97 in 1927 patients. Over time 238 children died (10.7%; 2.7% person-years [PY]) 63 were LTFU (2.8%; 0.7% PY). By multivariate analysis, mortality was associated with virus load (hazards ratio: 1.19; confidence interval: 1.01-1.402, P = 0.038) and reduced weight-for-age Z scores (hazards ratio: 0.590; confidence interval: 0.53-0.66, P < 0.001). LTFU was associated with low weight-for-height Z scores (hazards ratio: 0.71; confidence interval: 0.51-0.97, P = 0.031). At 12 months after combination antiretroviral therapy, anthropometric parameters significantly improved in 1226 children (P < 0.001); virus load declined to <400 copies/mL in over 60%. Despite advanced HIV disease, children initiating combination antiretroviral therapy had mortality rates of 2.7% p/PY with overall attrition rates of 11.7% p/100 PY, with significant reversal of negative anthropometric markers, and improvement of immunological and virological parameters in children with 12 months of follow-up.

In lower-income countries rates of AIDS-defining events (ADEs) and death are high during the first year of combination antiretroviral therapy (ART). We investigated differences between foreign-born (migrant) and native-born (nonmigrant) patients initiating ART in Europe, the US and Canada, and examined rates of the most common ADEs and mortality during the first year of ART. Observational cohort study. We studied HIV-positive adults participating in one of 12 cohorts in the Antiretroviral Therapy Cohort Collaboration (ART-CC). Of 48 854 patients, 25.6% were migrants: 16.1% from sub-Saharan Africa, 5.6% Latin America, 2.3% North Africa/Middle East, and 1.6% Asia. Incidence of ADEs during the first year of ART was 60.8 per 1000 person-years: 69.9 for migrants and 57.7 for nonmigrants [crude hazard ratio (HR) 1.18; 95% confidence interval (CI) 1.08-1.29], adjusted HR (for sex, age, CD4, HIV-1 RNA, ART regimen, prior ADE, probable route of infection and year of initiation, and stratified by cohort) 1.21 (95% CI 1.09-1.34). Rates of tuberculosis were substantially higher in migrants than nonmigrants (14.3 vs. 6.3; adjusted HR 1.94; 95% CI 1.53-2.46). In contrast, mortality was higher among nonmigrants than migrants (crude HR 0.71; 95% CI 0.61-0.84), although excess mortality was partially explained by patient characteristics at start of ART (adjusted HR 0.91; 95% CI 0.76-1.09). During the first year of ART, HIV-positive migrants had higher rates of ADEs than nonmigrants. Tuberculosis was the most common ADE among migrants, highlighting the importance of screening for tuberculosis prior to ART initiation in this population.

Loss to follow-up (LTFU) challenges the success of antiretroviral therapy (ART) scale-up among pediatric patients. Little is known about children who drop out of care. We aim to analyze risk factors for LTFU among children on ART, find their true outcomes through tracing, and investigate their final outcomes after resuming ART. This is a descriptive, retrospective, cohort study of children on ART between April 2006 and December 2010 in 2 clinics in urban Malawi. Routine data from an electronic data system were used and matched with information obtained through routine tracing procedures. Of 985 children (1999 child-years) on ART, 251 were LTFU: 12.6/100 child-years. At ART initiation, wasting [adjusted hazard ratio (AHR) 1.58 and 95% confidence interval (CI): 1.02 to 2.44] was independently associated with higher risk of LTFU. Of 201 LTFU children traced, 79% were found: 11% died, 25% stopped, 26% transferred-out, and 37% were still on ART. Median time between last visit and first tracing was 84 days (interquartile range: 64-101 days). Tracing reduced risk of LTFU by 38% (AHR 0.62 and 95% CI: 0.42 to 0.91) and decreased LTFU from 23.2% to 8.5%. Additional outcomes of stop, death, and transfer-out increased 4.4-fold, 1.8-fold, and 1.3-fold, respectively. Traced children with gaps in ART intake who resumed ART had higher risk of stopping (AHR 4.92 and 95% CI: 1.67 to 14.5) and transfer out (AHR 2.70 and 95% CI: 1.75 to 4.17) as final outcome. Early tracing substantially reduces LTFU; approximately one-third presumed LTFU was found to be still on ART. Children with wasting at initiation and those traced and found to have irregular ART intake require targeted interventions.

Little is known about the evolution of program outcomes associated with rapid expansion of antiretroviral therapy (ART) in resource-limited settings. We describe temporal trends and assess associations with mortality and loss to follow-up (LTFU) in HIV cohorts from 8 countries. Multicohort study using electronic health records. Analysis included adults in 25 Médecins Sans Frontières-supported programs initiating ART between 2001 and 2011. Kaplan-Meier methods were used to describe time to death or LTFU and proportional hazards models to assess associations with individual and program factors. ART programs (n = 132,334, median age 35 years, 61% female) expanded rapidly. Whereas 36-month mortality decreased from 22% to 9% over 5 years (≤2003-2008), LTFU increased from 11% to 21%. Hazard ratios (HR) of early (0-12 months) and late (12-72 months) LTFU increased over time, from 1.09 [95% confidence interval (CI): 0.83 to 1.43] and 1.04 (95% CI: 0.84 to 1.28) in 2004 to 3.29 (95% CI: 2.42 to 4.46) and 6.86 (95% CI: 4.94 to 9.53) in 2011, compared with 2001-2003. Rate of program expansion was strongly associated with increased early and late LTFU, adjusted HR (aHR) = 2.31 (95% CI: 1.78 to 3.01) and HR = 2.29 (95% CI: 1.76 to 2.99), respectively, for ≥125 vs. 0-24 patients per month. Larger program size was associated with decreased early mortality (aHR = 0.49, 95% CI: 0.31 to 0.77 for ≥20,000 vs. <500 patients) and increased early LTFU (aHR = 1.77, 95% CI: 1.04 to 3.04 for ≥20,000 vs. <500 patients). As ART expands in resource-limited settings, challenges remain in improving access to ART and preventing program attrition. There is an urgent need for novel and sustainable models of care to increase long-term retention of patients.

BackgroundIn Tanzania, loss to follow-up (LTFU) among adolescents and young adults living with HIV (AYLHIV) presents a significant challenge. A retrospective cohort study analysing data found that approximately 42% of adolescents on antiretroviral therapy (ART) were LTFU between 2014 to 2016. This study examined the predictors of LTFU among AYLHIV in Dar es Salaam during their first year of ART treatment.MethodsThis retrospective cohort study utilized routine data collected in care and treatment centres among adolescents and young adults aged 10–24 years living with HIV in Dar es Salaam who were enrolled in HIV care from 2015–2019. The data were analysed using STATA 14. Descriptive statistics were summarized using frequencies and proportions. Kaplan–Meier method was used to determine failure probabilities within one year of ART initiation. The Fine and Gray test was conducted to report adjusted sub-hazard ratios (aSHRs) and cumulative incidence estimates for LTFU within one year of ART initiation, accounting for mortality as a competing risk.ResultsA total of 15,874 AYLHIVs enrolled in Care and Treatment Clinics between 2015 and 2019 were studied. The majority (10,913, 68.7%) were young adults, and 13,160 (84.4%) were female. The percentage of LTFUs within one year of ART initiation was 15%. The significant predictors of LTFU were age 20–24 years, having a CD4 cell count between 350 and 499, receiving care in healthcare facilities located in the Ubungo district and being enrolled in care between 2018 and 2019. Receiving care at private healthcare facilities, having a tuberculosis co-infection, and being classified as WHO Stage III were all associated with a reduced risk of LTFU in ART care.ConclusionThis study found that adolescents and young people in Tanzania experience 15% rates of LTFU in ART care, within one year of ART initiation. Therefore, HIV service providers need to pay particular attention to the AYLHIV and factors that influence LTFU in ART care. The increasing incidence of LTFU necessitates the implementation of effective and friendly tracing interventions to identify AYLHIV patients who have become LTFU to re-engage them in care.

IntroductionLong-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet).MethodsWe assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen.ResultsA total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6–6.2). The median age at ART initiation was 36 years (IQR: 30–44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60–251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5–18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47–1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63–2.32) for 50 vs. 350 cells/µL; p<0.001) and older age (HR=1.47 (95% CI 1.29–1.69) for 50 vs. 30 years at ART initiation; p<0.001).ConclusionsIn this large, long-term study of mortality among HIV-positive adults initiating ART in Latin America and the Caribbean, overall estimates of mortality were heterogeneous, generally falling between those reported in high-income countries and sub-Saharan Africa.

Data on attrition due to mortality or loss to follow-up (LTFU) from antiretroviral therapy (ART) eligibility to ART initiation of HIV-infected children are scarce. The aim of this study is to describe attrition before ART initiation of 247 children who were eligible for ART in a cohort study in India. Multivariable analysis was performed using competing risk regression. The cumulative incidence of attrition was 12.6% (95% confidence interval, 8.7-17.3) after five years of follow-up, and the attrition rate was higher during the first months after ART eligibility. Older children (>9 years) had a lower mortality risk before ART initiation than those aged <2 years. Female children had a lower risk of LTFU before ART initiation than males. Children who belonged to scheduled tribes had a higher risk of delayed ART initiation and LTFU. Orphan children had a higher risk of delayed ART initiation and mortality. Children who were >3 months in care before ART eligibility were less likely to be LTFU. The 12-month risk of AIDS, which was calculated using the absolute CD4 cell count and age, was strongly associated with mortality. A substantial proportion of ART-eligible children died or were LTFU before the initiation of ART. These findings can be used in HIV programmes to design actions aimed at reducing the attrition of ART-eligible children in India.

BackgroundLoss to follow-up (LTF) challenges the reporting of antiretroviral treatment (ART) programmes, since it encompasses patients alive but lost to programme and deaths misclassified as LTF. We describe LTF before and after correction for mortality in a primary care ART programme with linkages to the national vital registration system.Methods and FindingsWe included 6411 patients enrolled on ART between March 2001 and June 2007. Patients LTF with available civil identification numbers were matched with the national vital registration system to ascertain vital status. Corrected mortality and true LTF were determined by weighting these patients to represent all patients LTF. We used Kaplan-Meier estimates and Cox regression to describe LTF, mortality among those LTF, and true LTF. Of 627 patients LTF, 85 (28.8%) had died within 3 months after their last clinic visits. Respective estimates of LTF before and after correction for mortality were 6.9% (95% confidence interval [CI] 6.2–7.6) and 4.3% (95% CI 3.5–5.3) at one year on ART, and 23.9% (95% CI 21.0–27.2) and 19.7% (95% CI 16.1–23.7) at 5 years. After correction for mortality, the hazard of LTF was reversed from decreasing to increasing with time on ART. Younger age, higher baseline CD4 count, pregnancy and increasing calendar year were associated with higher true LTF. Mortality of patients LTF at 1, 12 and 24 months after their last visits was respectively 23.1%, 30.9% and 43.8%; 78.0% of deaths occurred during the first 3 months after last visit and 45.0% in patients on ART for 0 to 3 months.ConclusionsMortality of patients LTF was high and occurred early after last clinic visit, especially in patients recently started on ART. Correction for these misclassified deaths revealed that the risk of true LTF increased over time. Research targeting groups at higher risk of LTF (youth, pregnant women and patients with higher CD4 counts) is needed.

With earlier antiretroviral therapy (ART) initiation, time spent in HIV care is expected to increase. We aimed to investigate loss to follow-up (LTFU) in Asian patients who remained in care 5 years after ART initiation. Long-term LTFU was defined as LTFU occurring after 5 years on ART. LTFU was defined as (1) patients not seen in the previous 12 months; and (2) patients not seen in the previous 6 months. Factors associated with LTFU were analysed using competing risk regression. Under the 12-month definition, the LTFU rate was 2.0 per 100 person-years (PY) [95% confidence interval (CI) 1.8-2.2 among 4889 patients included in the study. LTFU was associated with age > 50 years [sub-hazard ratio (SHR) 1.64; 95% CI 1.17-2.31] compared with 31-40 years, viral load ≥ 1000 copies/mL (SHR 1.86; 95% CI 1.16-2.97) compared with viral load < 1000 copies/mL, and hepatitis C coinfection (SHR 1.48; 95% CI 1.06-2.05). LTFU was less likely to occur in females, in individuals with higher CD4 counts, in those with self-reported adherence ≥ 95%, and in those living in high-income countries. The 6-month LTFU definition produced an incidence rate of 3.2 per 100 PY (95% CI 2.9-3.4 and had similar associations but with greater risks of LTFU for ART initiation in later years (2006-2009: SHR 2.38; 95% CI 1.93-2.94; and 2010-2011: SHR 4.26; 95% CI 3.17-5.73) compared with 2003-2005. The long-term LTFU rate in our cohort was low, with older age being associated with LTFU. The increased risk of LTFU with later years of ART initiation in the 6-month analysis, but not the 12-month analysis, implies that there was a possible move towards longer HIV clinic scheduling in Asia.