HIV-1 subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics

Abstract

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes.

Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots.

Conclusions: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients.

Figure 1

Proportion of diagnoses with subtype B by country of sampling of the patient. AT – Austria (n=99), BE – Belgium (n=220), CY – Cyprus (n=24), DK – Denmark (148), FI – Finland (n=48), DE – Germany (n=364), GR – Greece (251), IE – Ireland (n=38), IT – Italy (199), LU – Luxembourg (n=35), NL – Netherlands (n=97), NO – Norway (n=94), PL – Poland (n=121), PT – Portugal (n=240), SI – Slovenia (n=62), ES – Spain (n=206), SE – Sweden (n=210), CS – Serbia (n=67), CZ – Czech Republic (n=143), SK – Slovakia (n=11), IL – Israel (n=43).

Figure 2

Subtype distribution stratified by continent of origin of the patient. Regional distribution of the countries was defined as in the UNAIDS reports (Hemelaar, et al., 2006): Sub-Saharan Africa (S-S A, n=330), East Asia (n=2), Oceania (n=1), South and South-East Asia (S/S-E A, n=61), Eastern Europe and Central Asia (EE/CA, n=425), Western Europe (WE, n=1636), North Africa and Middle East (NA/ME, n=36), North America (n=7), Caribbean (n=11), Latin America (LA, n=55). Due to the low sample size, East Asia and Pacific, Oceania, North America and Caribbean are not included in the figure. See Additional file 5: Table S5 for list of countries included in each continent region.

Figure 3

Subtype distribution by gender. A total of 307 females (blue bars) and 989 males (red bars) were included in the analysis. For 4 patients, this information was not available; and these were deleted from the data set. Asterisks indicate statistically significant differences in the proportion of a certain subtype in male vs. female (p<0.05).

Figure 4

Proportion of diagnoses with different HIV-1 subtypes in different risk groups. IDUs (green bars) – intravenous drug users (n=221); Homo-bi (red bars) – homobisexuals (n=1271); Hetero (blue bars)– heterosexuals (n=994). Asterisks indicate significant differences in the proportion of one subtype between at least two of the risk groups. For example, for URFs the significant difference was found only between homosexuals and heterosexuals (p=1.2x10-5) while subtype B has a significantly different frequency in all risk groups. For more details, please refer to the methods and results sections.

Figure 5

Bayesian networks of the variables that were found to be associated with the subtype of the HIV-1 strain in the univariate analysis. The variables gender, risk group and continent of origin were grouped as described previously. Black arcs indicate variables directly associated with the Subtypes/CRFs variable. Grey arcs indicate indirect association with Subtypes/CRFs. Dotted arcs indicate associations with low bootstrap support (<70%), while full arcs indicate associations confirmed by a high bootstrap support (>70%). Country of sampling included 20 countries: Austria, Belgium, Cyprus, Denmark, Finland, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Norway, Poland, Portugal, Slovenia, Spain, Sweden, Serbia, Czech Republic, Slovakia and Israel. Country of origin included: Netherland Antilles, Angola, Argentina, Austria, Belgium, Burkina Faso, Burundi, Benin, Brasil, Democratic Republic of Congo, Congo, Switzerland, Cote D’Ivoire, Chile, Cameroon, China, Colombia, Cuba, Cape Verde, Cyprus, Czech Republic, Germany, Djibouti, Denmark, Dominican Republic, Algeria, Equator, Estonia, Egypt, Eritrea, Spain, Ethiopia, Finland, France, United Kingdom, Georgia, Ghana, Gambia, Guinea, Equatorial Guinea, Greece, Guinea-Bissau, Croatia, Ireland, Israel, India, Iraq, Iran, Iceland, Italy, Kenya, South Korea, Liberia, Luxembourg, Latvia, Libyan Arab Jamahiriya, Morocco, Myanmar, Mauritania, Mexico, Malaysia, Mozambique, Niger, Nigeria, Netherland, Norway, New Zealand, Oman, Peru, Pakistan, Poland, Portugal, Romania, Russia, Rwanda, Sudan, Sweden, Singapore, Slovenia, Slovakia, Sierra Leone, Senegal, Somalia, Suriname, Sao Tome and Principe, Syrian Arab Republic, Togo, Thailand, Tunisia, Tonga, Turkey, Tanzania, Ukraine, Uganda, USA, Uruguay, Venezuela, Serbia, Zambia, Zimbabwe and South Africa. However, only to keep the number of instances in the variable country of origin similar to the number of instance in the variable country of sampling; only instances of Austria, Belgium, Cameroon, CS (Serbia), Czech Republic, Germany, Denmark, Spain, Ethiopia, Finland, Greece, Italy, Nigeria, The Netherlands, Norway, Poland, Portugal, Sweden, Slovenia, Thailand and Yugoslavia were left ungrouped; while all other instances of country of origin with smaller sample size were group together.

Figure 6

Proportion of different HIV-1 subtypes stratified according to year of diagnosis. In 2002, samples were collected only during the last 3 months, and therefore this year was excluded from the analysis. 909 samples were collected in 2003, 1107 in 2004 and 513 in 2005. Significance for increasing or decreasing trends was tested with the Cohran-Armitage test. Significant trends are indicated in the figure with an asterisk. p-values are described in the text.