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Temporal changes in ART initiation in adults with high CD4 counts in Latin America: a cohort study
Brenda E Crabtree-Ramírez1, Yanink Caro-Vega1, Pablo F Belaunzarán-Zamudio1
1Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición, México City, Mexico.
Insights
Combination ART (cART) initiation in HIV patients accelerated significantly in Latin America following WHO guideline updates. However, many patients still do not start cART, highlighting the need for improved treatment access and retention strategies.
Area of Science:
- Infectious Diseases
- Public Health
- Epidemiology
Background:
- World Health Organization (WHO) updated combination antiretroviral therapy (cART) guidelines in 2013 and 2015, recommending earlier initiation for HIV-positive individuals.
- The real-world implementation and impact of these guideline changes in Latin America remained unevaluated.
Purpose of the Study:
- To assess trends in the time from enrollment in care to cART initiation among HIV-positive adults with high CD4 counts in Latin America.
- To evaluate the impact of WHO guideline updates on cART initiation practices in routine HIV care settings.
Main Methods:
- Analysis of data from the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) from 2003 to 2017.
- Inclusion of cART-naive adults (≥18 years) with CD4 counts ≥350 cells/mm³ and no AIDS at enrollment.
- Kaplan-Meier and Cox proportional hazards models were used to estimate time to cART initiation and associated trends.
Main Results:
- Median time to cART initiation decreased significantly after 2013 and 2015, aligning with WHO guideline updates.
- The probability of cART initiation substantially increased in recent years, with hazard ratios significantly higher post-2013 and post-2015 compared to 2003.
- A considerable proportion of patients (24%) never initiated cART, with high rates of loss to follow-up and death among this group.
Conclusions:
- Time to cART initiation has decreased in Latin America, reflecting adherence to updated WHO guidelines.
- Despite improved initiation trends, a significant number of patients are not retained in care or initiated on treatment, underscoring the need for enhanced early treatment strategies and retention efforts.
Introduction:
In 2013, the World Health Organization (WHO) recommended initiating combination ART (cART) in all adults with HIV and CD4+ lymphocyte counts (CD4) <500 cells/mm3 . In 2015, this was updated to recommend cART initiation in all patients with HIV, regardless of CD4 count. Implementation of these guidelines in real-world settings has not been evaluated in Latin America. To assess changes in time to cART initiation during routine care, we estimated trends in time from enrolment in care to cART initiation in HIV-positive adults with high CD4 counts in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) during 2003 to 2017.
Methods:
All cART-naive individuals ≥18 years of age from 2003 to 2017 with CD4 ≥350 cells/mm3 and without AIDS at enrolment at five CCASAnet sites (Brazil, Chile, Honduras, Mexico and Peru) were included. Patients without information regarding AIDS-defining events were excluded. We estimated unadjusted median time from enrolment to cART initiation by calendar year using Kaplan-Meier methods and calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for trends in cART initiation using Cox models and restricted cubic splines for continuous variables, accounting for age, sex, CD4 at enrolment, route of HIV transmission and clinic site.
Results:
Of the 3171 patients included, 1,650 (52%) had CD4 ≥500 cells/mm3 at enrolment. Median time to cART initiation after 2013 was 6.21 weeks (interquartile range (IQR): 1.89, 23.21), and 4.71 weeks (IQR: 1.43, 9.57) after 2015. Among 763 (24%) patients who never initiated cART, 33 (4.3%) were reported as deceased, 481 (63%) were lost to follow-up, and 249 (33%) were administratively censored before initiation. Adjusted probability of cART initiation greatly increased in recent years, in particular after 2013 and 2015 (2013 vs. 2003: HR = 7.14; 95% CI: 5.84 to 8.73, and 2015 vs. 2003: HR = 12.60; 95% CI: 10.37 to 15.32).
Conclusions:
Time to cART initiation decreased substantially, roughly following changes in WHO guidelines in this real-world setting in Latin America. However, a very high proportion of patients never started cART, compromising retention in care and survival, as shown by their higher proportion of LTFU and death, which reinforce the notion that earlier treatment implementation strategies are needed.
