Recent HIV-1 Outbreak Among Intravenous Drug Users in Romania: Evidence for Cocirculation of CRF14_BG and Subtype F1 Strains

Abstract

Since 2011, Romania has faced an HIV outbreak among injecting drug users (IDUs). Our aim was to identify and describe clinical and epidemiological patterns of this outbreak. A cross-sectional study enrolled 138 IDUs diagnosed with HIV infection between 2011 and 2013 with 58 sexually infected individuals included as the control group. The IDUs had a long history of heroin abuse (10 years) and a recent history of new psychostimulant injection (3-4 years). Classical epidemiological data and molecular techniques were used to describe the transmission dynamics. A high prevalence of hepatitis C virus (HCV) coinfection was noted (98.6%) compared to the control group (10.3%) ( p < 0.001). IDUs had initially been infected with HCV. HIV infection was more recent, linked to starting injecting stimulants. HIV subtype analysis showed a predominance of the local F1 strain in both IDUs and sexually infected patients; in IDUs it also identified 28 CRF14_BG recombinants and six unique recombinant forms (URFs) between F1 and CRF14_BG. A few patients from both risk groups were infected with subtype B. Among IDUs, CRF14_BG was associated with a lower CD4 cell count and more advanced stages of disease, which correlated with CXCR4 tropism. Phylogenetic analysis revealed the spread of HIV through three major IDU clusters of recent date. Among IDUs with CRF14_BG, some reported travel abroad (Spain, Greece). By identifying clusters of IDUs with related viruses, molecular epidemiologic methods provide valuable information on patterns of HIV transmission that can be useful in planning appropriate harm reduction interventions.

Enhanced HIV-1 surveillance using molecular epidemiology to study and monitor HIV-1 outbreaks among intravenous drug users (IDUs) in Athens and Bucharest

“…These numbers corresponded to 19.8% (122/616) newly reported HIV(+) IDUs diagnoses during the same time period in Romania. Demographic, epidemiological and clinical data for these patients were presented previously (Niculescu et al, 2014).…”

“…In addition to the outbreak sequences (N = 122), other HIV sequences were included in the phylogenetic analysis: 107 sequences for the CRF14_BG analysis and 924 sequences for the subtype F1 analysis (Niculescu et al, 2014). For the CRF14_BG we used all publicly available sequences in protease (PR) and partial reverse transcriptase (RT) (http:// www.hiv.lanl.gov/) regions (Sampled regions: Spain, a Romanian non-IDU and the outbreak sequences from Greece).…”

Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects

“…Our findings provide insights on the dynamics of recently emerging HIV outbreaks such as those in Athens [8], Romania [9], or Indiana [26]. Crucially, HIVepidemics in PWID have been recently emerging in resource-limited countries in the Middle East and north Africa (particularly Afghanistan, Egypt, and Morocco) [5], as well as in some southeast Asian countries (e.g.…”

“…The epidemic in these countries has been accompanied by very limited harm reduction services [4], making it a large-scale 'natural experiment' of HIV spread among PWID. By studying the epidemiological dynamics of the largest HIV epidemic among PWID, we might understand epidemics emerging in countries of the Middle East and northern Africa [5,6], southeastern Asia [7], Europe [8,9], and the USA [10]. Critically, although harm reduction approaches among PWID since the 1980s have had significant effects in the developed world [11], it remains unclear whether these preventive strategies should be prioritized over newer approaches such as treatment as prevention (TasP) [12] in resource-limited settings.…”

Reconstructing contact network parameters from viral phylogenies

“…This kind of growth curve has three qualitative phases: exponential growth, linear growth, and a slow final phase when the susceptible population is almost depleted. The waiting times until the next transmission, which determine the coalescence times in the tree, are MSM/USA (Little et al 2014) MSM/Taiwan (Kao et al 2011) MSM/Beijing (Wang et al 2015) HET/Uganda (Grabowski et al 2014) HET/Malawi (McCormack et al 2002) HET/Botswana (Novitsky et al 2013(Novitsky et al & 2014 IDU/Romania (Niculescu et al 2015) IDU/Estonia (Zetterberg et al 2004) dependent on the growth phase of the epidemic. Therefore, we hypothesize that it is the growth phase at the time of sampling which most affects tree shape, rather than the specific values of I or N ( Supplementary Fig.…”