Emergence as an outbreak of the HIV-1 CRF19_cpx variant in treatment-naïve patients in southern Spain

Abstract

Background: CRF19_cpx is a complex circulating recombination form (CRF) of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain.

Methods: The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain). Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data.

Results: Between 2011 and 2016, we detected 57 treatment-naïve patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART) responded.

Conclusions: We report the largest HIV-1 CRF19_cpx cohort of treatment-naïve patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.

Fig 1. Cases of CRF 19_cpx subtype over time.

Number of CRF19_cpx variants detected in the Hospital Virgen de la Victoria, from the first case found until the end of the study period (2011–2016).

Fig 2. Bayesian maximum clade credibility phylogenetic tree inferred by MrBayes v3.2 program showing our CRF19_cpx sequences and another 254 reference sequences from the same variant retrieved from LANL.

Each patient from our cohort is represented in red by their sample ID, while reference sequences appear in different colours according to the country of sampling (green: Cuba; pink: United Kingdom; turquoise: Spain (other than our cohort); brown: USA; black: Greece; blue: Tunisia). This figure is depicted in detail as a supplementary material (S2 Fig).

Fig 3. Subtree with the 55 CRF19 cpx sequences grouped together (pp = 0.895) conforming the identified outbreak as depicted in Bayesian inference of the phylogeny (see Fig 2).

Sequences presenting the G190A mutation are highlighted within the light grey shaded square. Asterisks indicate the detection of V179I/A as applicable.