HIV Insight: Economic and Epidemiological Impact of Early Antiretroviral Therapy Initiation in India

Recent WHO guidance advocates for early antiretroviral therapy (ART) initiation at higher CD4 counts to improve survival and reduce HIV transmission. We sought to quantify how the cost-effectiveness and epidemiological impact of early ART strategies in India are affected by attrition throughout the HIV care continuum.

We constructed a dynamic compartmental model replicating HIV transmission, disease progression and health system engagement among Indian adults. Our model of the Indian HIV epidemic compared implementation of early ART initiation (i.e. initiation above CD4 ≥350 cells/mm³) with delayed initiation at CD4 ≤350 cells/mm³; primary outcomes were incident cases, deaths, quality-adjusted-life-years (QALYs) and costs over 20 years. We assessed how costs and effects of early ART initiation were impacted by suboptimal engagement at each stage in the HIV care continuum.

Assuming “idealistic” engagement in HIV care, early ART initiation is highly cost-effective ($442/QALY-gained) compared to delayed initiation at CD4 ≤350 cells/mm³ and could reduce new HIV infections to <15,000 per year within 20 years. However, when accounting for realistic gaps in care, early ART initiation loses nearly half of potential epidemiological benefits and is less cost-effective ($530/QALY-gained). We project 1,285,000 new HIV infections and 973,000 AIDS-related deaths with deferred ART initiation with current levels of care-engagement in India. Early ART initiation in this continuum resulted in 1,050,000 new HIV infections and 883,000 AIDS-related deaths, or 18% and 9% reductions (respectively), compared to current guidelines. Strengthening HIV screening increases benefits of earlier treatment modestly (1,001,000 new infections; 22% reduction), while improving retention in care has a larger modulatory impact (676,000 new infections; 47% reduction).

Early ART initiation is highly cost-effective in India but only has modest epidemiological benefits at current levels of care-engagement. Improved retention in care is needed to realize the full potential of earlier treatment.

Below: Model schematic of HIV transmission, disease progression and engagement in HIV care continuum. The Indian population is divided into compartments stratified by HIV serostatus, stage of HIV infection, and engagement with HIV care continuum. Each compartment is further stratified by gender and risk group (heterosexual, MSM, PWID and high-risk individuals [e.g. FSW]). The model incorporates HIV transmission through sexual intercourse and injection drug use. Arrows represent rates of flow between compartments; values are shown in Table 1. +, HIV-infected individuals; −, HIV-uninfected individuals; ART, HIV-infected individuals on first- or second-line antiretroviral therapy. At any point in the care continuum, PLWH can progress through stages of HIV from acute HIV to AIDS if not on ART (shown in inset). Individuals experience immunological recovery if on ART and virologically suppressed.

Below: Sensitivity analysis for incremental cost-effectiveness ratio comparing early ART initiation with current practices of ART initiation (CD4 ≤350 cells/mm3) within the context of a “realistic” continuum of care. Solid vertical line represents base ICER ($530 per QALY-gained). Blue bars indicate low values of parameter range; red bars indicate high values of parameter range.

Below: Epidemiological impact of delayed ART initiation (CD4 ≤350 cells/mm3), early ART initiation and early ART initiation in combination with various interventions in the HIV care continuum. “Delayed ART initiation” represents current practice and incorporates the current HIV care continuum with suboptimal screening, linkage and retention in care. “Early ART initiation” represents increased rates of ART initiation at CD4 >350 cells/mm3, but assumes continuation of current levels of care-engagement. “Expanded screening” involves annual screening of high-risk groups, with 95% linkage to care. “Improved detection of virological failure” involves detecting ART failure and modifying treatment promptly (within six months of virological failure). “Improved retention in care” is defined as optimal retention of PLWH in care (annual disengagement rate of 2.5% and reengagement within one year of disengagement).