Timeliness of antiretroviral therapy initiation in the era before universal treatment

Abstract

We assessed the prevalence and factors related to the time to antiretroviral (ART) initiation among persons who entered HIV care and subsequently started ART in Croatia from 2005 to 2014. Included were patients ≥ 18 years, the follow-up ended on Dec/31/2017. 628 patients were included into the study 91.9% were men; median age was 36.1 (Q1-Q3: 29.6-43.8) years. Rapid (within 7 days of diagnosis) ART initiation was observed in 21.8% patients, 49.8% initiated ART within 30 days, 21.7% and 28.5% had intermediate (31 days-1 year) and late initiation (> 1 year), respectively. Of 608 patients that achieved an undetectable viral load, 94% had a plasma HIV-1 RNA < 50 copies/ml at last measurement after a median follow-up of 5.2 years. On quantile regression analysis, calendar year of entry into care, and markers of more advanced HIV disease (higher viral load, lower CD4 cell count and clinical AIDS) were significantly associated with earlier ART initiation. Early ART was not related to a gap in care afterwards at all quantiles. In conclusion, a significant proportion of patients started ART early in Croatia in 2005-2014. Early ART initiation led to durable viral load suppression and was not associated with a subsequent gap in care.

Figure 1

Time from HIV diagnosis to antiretroviral therapy (ART) initiation according to study periods. (a) Shows the frequency distribution of time from HIV diagnosis to ART initiation and (b) shows the frequency distribution of time from entry into care to ART initiation.

Figure 2

Kaplan–Meier plots of time from HIV diagnosis to undetectable plasma HIV-RNA: (a) overall; (b) according to gap in care; (c) by period of ART initiation; and (d) timeliness of ART initiation (rapid = within 7 days early = 8 to 30 days, intermediate = 31 days to one year, late > 1 year).

Figure 3

Multivariable quantile regression exploring time from ART initiation and potential related factors. The x-axis represents quantiles of the distribution of the time to ART initiation (log-time in months), and the y-axis represents the parameter estimates (coefficients) change in time associated with a one-unit change of the studied covariate, holding other covariates constant. This change is considered significant at a particular quantile when the associated 95% confidence interval (shaded area) does not cross the 0 line. Integration into care was modeled as log-days.

Figure 4

Flow diagram of participants included into the study. HIV human immunodeficiency virus; UHID University Hospital for Infectious Diseases, Zagreb, Croatia; ART antiretroviral treatment; LTFU lost to follow-up.