This analysis of 694,138 medical records from 10 low- and middle-income countries (LMIC), contributes several findings relevant for ART programs in resource-limited settings. Observed declines in the prevalence of advanced disease at ART initiation in eight countries and increases in median baseline CD4 at ART initiation in six countries are likely due to increasing access to HIV testing and treatment (e.g., increasing numbers of facilities providing testing and treatment services), and increasingly inclusive ART eligibility guidelines (1). Despite this encouraging progress, however, a significant percentage of ART enrollees still started ART with advanced disease in recent years. In Haiti, which provided the most recent data on ART enrollees for this analysis (2015), and which historically has had higher than average median CD4 at ART initiation compared with other LMIC (Table 2) (2,3), the percentage of ART enrollees with CD4 <200/μL was 34% in 2015. Similarly, in Mozambique in 2014, 37% of patients started ART with advanced disease. Although recent data from the 10 countries are limited, these data and data from a recent meta-analysis, which reported mean CD4 count at ART initiation for 27 LMIC in 2011–2013 of 186 cells/μL (3), suggest at least a third of ART patients in LMIC initiated ART with advanced disease in 2015. To reduce prevalence of advanced disease at ART initiation in LMIC, continued attention to programmatic strategies facilitating earlier HIV testing and linkage to care are needed, in addition to adoption of WHO-recommended universal ART eligibility (“treat-all”) guidelines for persons living with HIV (3), which stipulate that all patients become eligible for ART on the day of HIV diagnosis, regardless of CD4 count at HIV diagnosis. Early ART for all persons living with HIV could improve ART program outcomes and HIV prevention impact (4,5). For example, in the Strategic Timing of Antiretroviral Therapy (START) trial, initiating ART for patients with CD4 >500/μL rather than deferring ART initiation until more advanced disease stages, was shown to reduce risk for a composite endpoint of any serious acquired immunodeficiency syndrome (AIDS)–related event, non-AIDS–related event, or death by 57% (5). In addition, early rather than deferred ART for HIV-positive persons in a serodiscordant relationship was found to reduce HIV transmission to the HIV-negative partner by approximately 96% (4). Among the 10 countries studied, “treat-all” guidelines have been adopted nationwide in nine (Haiti, Mozambique, Namibia, Nigeria, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe), whereas Vietnam is beginning to phase in “treat-all” guidelines with nationwide adoption planned by 2020.

Given the low median baseline CD4 from Vietnam in 2009 (92/μL), much lower than Haiti’s median baseline CD4 the same year (219/μL), evaluation of more recent trends in baseline CD4 is warranted. With Vietnam’s epidemic largely involving men who inject drugs, late presentation for ART might be partly explained by suboptimal health-seeking behavior in this population (6). In Vietnam and similar LMIC, continued monitoring of the prevalence of advanced HIV disease at ART initiation is necessary to inform understanding of ART program access, outcomes, and prevention strategies (because baseline CD4 gives an indication of how long ART enrollees have lived with an unsuppressed viral load). Comparing prevalence of advanced disease at ART initiation among demographic groups (e.g., nonpregnant females, pregnant females, and males) or among more affected population groups (e.g., sex workers and persons who inject drugs) can inform which populations are being reached late and therefore require targeted interventions (1).

Recent WHO guidelines recommend a differentiated approach to treatment of persons living with HIV.^¶ This approach means that patients initiating ART with advanced HIV disease require additional specialized care to ensure optimal outcomes. For example, tuberculosis (TB) is common among patients starting ART with advanced HIV disease, and remains the most common cause of death, accounting for approximately 40% of deaths, half of which are undiagnosed before death (7). Based on recent evidence from a randomized trial (8), WHO recommends that the lateral flow urine lipoarabinomannan assay may be used to assist in the rapid diagnosis and treatment of disseminated TB among persons living with HIV admitted to hospital with CD4 <100/μL and symptoms of TB. WHO conditionally recommends the same screening approach for adult outpatients. Early identification and treatment of disseminated TB can reduce all-cause mortality (8). In addition, plasma screening for cryptococcal antigen (CrAg) among patients with CD4 <100/μL and consideration of preemptive treatment with fluconazole for CrAg-positive patients might reduce 12-month ART mortality (9). Co-trimoxazole prophylaxis for ART enrollees with CD4 <350/μL has been shown to reduce mortality (10). Use of these adjunctive therapies could help reduce relatively high 12-month mortality among people taking ART in LMIC (1).

Given the importance of baseline CD4 in determining eligibility for adjunctive therapies that have the potential to reduce mortality, it is concerning that 40% of the 694,138 medical records reviewed lacked documentation of the baseline CD4, with country-specific rates ranging from 9% in Swaziland to 53% in Zimbabwe. Quality improvement measures to ensure availability of baseline CD4 data for clinical decision-making are warranted.

The findings in this report are subject to at least three limitations. First, cohort data varied in size and generalizability; statistical significance of trends in baseline CD4 over time is more likely with larger sample sizes and more calendar years of available data. Second, missing data on CD4 at ART initiation might have introduced measurement error for summary estimates. Third, in several countries, data on more recent ART enrollees are needed to inform estimates of the current prevalence of advanced HIV disease at ART initiation.

Encouraging reductions in the prevalence of advanced disease at ART initiation were observed in eight of the 10 countries studied. This reflects the rapid scale-up of HIV testing and treatment services in LMIC since 2004 and evolution of HIV treatment guidelines encouraging earlier ART initiation. However, an estimated one third of new ART enrollees in LMIC in 2015 started ART with advanced disease, indicating that continued scale-up of interventions to facilitate earlier testing and treatment are needed. For those ART enrollees who do initiate ART late (3), ensuring availability of WHO-recommended adjunctive therapies could help reduce morbidity and mortality during ART.