Infection with HIV-1 subtype D adversely affects the live expectancy independently of antiretroviral drug use

Abstract

Introduction: HIV-1 subtypes have been associated with less favourable clinical profiles, differences in disease progression and higher risk of neurocognitive deficit. In this study we aimed to analyse the long term survival disparities between patients infected with the most common HIV-1 variants observed in Poland.

Methods: For the study data from 518 Caucasian non-immigrant patients of Polish origin infected with divergent HIV subtypes and variants [subtype A (n = 35, 6.8%), subtype B (n = 386, 74.5%), subtype C (n = 13, 2.5%), subtype D (n = 58, 11.19%) or other non-A,B,C,D (n = 26, 5.01%)variants] were analysed. Subtyping was performed using the partial pol (reverse transcriptase and protease) sequencing. HIV variant was coupled with clinical, virologic and survival data censored at 20 years of observation. Overall survival and on antiretroviral treatment survival was analysed using Kaplan-Meyer as well as unadjusted and multivariate Cox proportional hazards models.

Results: Significantly higher mortality was observed among subtype D (28.8%) infected subjects compared to subtype B (11.7%, p = 0.0004). Increased risk of death among subtype D cases remained significant when cART treated individuals were analysed, with on-treatment mortality of 26.9% for subtype D (p = 0.006) compared to 10.73% in subtype B infected cases. Kaplan-Meyer survival estimates differed significantly across all investigated HIV-1 variant groups when overall 20 year mortality was analysed (log rank p = 0.029), being non-significant for the cART treated group. In multivariate model of overall 20 year survival, adjusted for age at diagnosis, gender, HCV and AIDS status, lymphocyte CD4 count, transmission route and HIV viral load, only age and subtype D were independently associated with higher likelihood of death [HR: 1.08 (95%CI: 1.03-1.14, p = 0.002) and HR: 7.91 (95%CI:2.33-26.86), p < 0.001, respectively]. In the on-treatment (cART) multivariate model of 20 year survival adjusted for the same parameters only subtype D remained as the independent factor associated with higher mortality risk [HR: 4.24 (95%CI:1.31-13.7), p = 0.02].

Conclusions: Subtype D has an independent deleterious effect of survival, even in the setting of antiretroviral treatment. Observed effect indicated higher clinical vigilance for patients infected with this subtype even after long time of stable antiretroviral treatment.

Keywords: Mortality risk; Subtype D; Survival.