Date Published: July 10, 2017
Publisher: Public Library of Science
Author(s): Terra V. Fatukasi, Stephen R. Cole, Richard D. Moore, William C. Mathews, Jessie K. Edwards, Joseph J. Eron, Dimitrios Paraskevis.
Prompt initiation of combination antiretroviral therapy (ART) is important to reduce comorbidity and mortality among people living with HIV, especially for those with a low CD4 cell count. However there is evidence that not everyone receives prompt initiation of ART after enrolling into HIV care. The current study investigated factors associated with failure to initiate ART within two years of entering into care among those with a CD4 count at or below 350 cells/mm3. The sample included 4,907 ART-naive patients with a CD4 count at or below 350 cells/mm3 enrolled between January 1, 2003 and December 31, 2012 at any of eight clinical sites in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). The two-year risk of delayed ART initiation was estimated using a log-binomial regression model with stabilized inverse probability of censoring weights for those lost to follow-up. Adjusting for other factors, an earlier enrollment date was the sole demographic characteristic associated with an increased risk of delayed ART initiation. Higher CD4 count, lower viral load, and a prevalent AIDS diagnosis were clinical characteristics associated with delayed ART initiation. Gender, age, race/ethnicity and HIV risk factors such as reported male-to-male sexual contact and injection drug use were not associated with delayed ART initiation. This study identified characteristics of patients for whom treatment was strongly to moderately recommended but who did not initiate ART within two years of entering care. Despite the known benefits of early antiretroviral therapy initiation, a lower viral load measurement may continue to be an important clinical characteristic in the more recent era with current ART initiation guidelines. These findings provide a target for closer monitoring and intervention to reduce disparities in HIV care.
Despite the introduction of effective combination antiretroviral therapy (ART) for HIV in 1996 , HIV continues to be a global health crisis. For example, in 2014, the United States Centers for Disease Control and Prevention (CDC) estimated 1.2 million US persons living with HIV and 12,333 AIDS-related deaths . The use of ART has led to an increase in life expectancy among HIV-seropositive individuals through a reduction in HIV-associated comorbidity, as well as non-HIV and non-AIDS comorbidities [3–6]. The difference in life expectancy between HIV-seropositive and HIV-seronegative individuals is shrinking, though specific populations still exhibit notable differences [3, 6]. For example, among HIV-seropositive patients on ART, those with a history of injection drug use, a lower baseline CD4 count, and who are non-white have lower life expectancies relative to other groups [3, 6]
The distribution of demographic characteristics for the sample at CNICS enrollment is displayed in Table 1. The majority of patients were men (83%; n = 4,084) and the prevalence of male-to-male sexual contact was 60% (n = 2,925). Thirteen percent (n = 654) of patients reported injection drug use and 29% (n = 1,432) of patients had a prevalent AIDS diagnosis at their CNICS enrollment. The median CNICS enrollment year was 2007 (IQR: 2005, 2010) and 18% of patients were at least 50 years of age. Forty-two percent of patients had a viral load ≥100,000 copies/mL and 59% of patients had a CD4 cell count below 200 cells/mm3. The most common racial groups were white non-Hispanic at 41%, black non-Hispanic at 40%, and Hispanic at 13%.
We found that among ART-naïve patients with CD4 count at or below 350 cells/mm3, higher CD4 count, lower viral load, a prevalent AIDS diagnosis, and an earlier CNICS enrollment date were each independently associated with failure to initiate ART within the first two years after enrollment in CNICS between January 1, 2003 and October 1, 2012. Lower viral load was the sole clinical factor to remain associated with failure to initiate ART over the entire study period. Female gender, older age, black race/ethnicity, reported injection drug use, and lack of reported male-to-male sexual contact were demographic characteristics associated with delayed ART initiation in the unadjusted analysis, but did these associations did not persist after adjustment for other demographic and clinical characteristics.
This study identified characteristics of patients who delay ART initiation beyond the first two years of entering in care, which included an earlier CNICS enrollment date, higher CD4 count, lower viral load, and a prevalent AIDS diagnosis. This prolonged delay in ART initiation among patients with a moderate to strong recommendation under past guidelines suggests that treatment practice under current guidelines recommending therapy initiation to all HIV-seropositive patients should be carefully scrutinized. The tendency to delay therapy in those patients with a lower viral load may still persist despite clear evidence of the benefits of immediate therapy initiation . These clinical characteristics may continue to be important with current ART guidelines in providing targets for closer monitoring and intervention to reduce disparities in HIV care.