Bridging epidemiology with population genetics in a low incidence MSM-driven HIV-1 subtype B epidemic in Central Europe.

BACKGROUND: The HIV-1 epidemic in Slovenia, a small Central European country, has some characteristics that make it an ideal model to study HIV-1 transmission. The epidemic is predominantly affecting men who have sex with men infected with subtype B (89% of all patients), has a low prevalence (less than 1/1000) and is growing slowly. The aim of the present study was to analyze in detail the evolutionary history and the determinants of transmission. METHODS: A total of 223 partial pol gene sequences from therapy naïve individuals were included, representing 52% of all patients newly diagnosed in 13 years (2000-2012) and analyzed together with genetically similar worldwide sequences, selected in a BLAST search. RESULTS: Combined analysis (maximum likelihood and Bayesian) of HIV-1 transmission chains revealed 8 major clusters (n ≥ 10 patients), 1 group of 4 patients, 2 trios and 12 transmission pairs, thus leaving only 43 (19.3%) Slovenian patients infected with subtype B without a local epidemiological link, indicating a predominance of local transmission of HIV-1 infection. Bayesian analysis performed on a full set of sequences estimated several introductions of HIV-1 into Slovenia, with the most recent common ancestor (tMRCA) of the earliest Slovenian cluster dated to the late 1980s, although tMRCAs obtained from separate independent analysis of each cluster showed considerably more recent estimates. These findings indicate inconsistencies in molecular clock estimation, which we further explored. We hypothesize that these inconsistent dating estimates across the tree could be caused by an evolutionary rate acceleration of HIV-1 after entering the Slovenia epidemic that is not taken into account by the molecular clock model. It could be caused by a lower transmission rate in this setting, as demonstrated by the low epidemic growth rate estimated by Bayesian skyline plot analysis. CONCLUSIONS: HIV-1 subtype B was introduced into Slovenia at several time points from the late 80s onward. The majority of patients had a local transmission link, indicating a closed HIV community. The observed slower epidemic rate suggests that individuals with a long-lasting infection are the driving force of the epidemic in this region.

Prevalence and risk factors for osteopenia/osteoporosis in an HIV-infected male population.

The objective of our investigation was to estimate the prevalence of osteopenia/osteoporosis in men with HIV/AIDS and evaluate the role of antiretroviral treatment (ART), HIV and other risk factors in reducing bone mineral density (BMD). All known Slovenian HIV-infected ART-naïve and treated males (infected or treated > 12 months) were invited to participate in a cross-sectional study. Data were collected on age, BMI, waist-hip ratio, family history of hip fracture, duration of infection, duration of ART, smoking, alcohol, exercise, viral load and CD4+ cells. BMD was measured using dual X-ray absorptiometry. A total of 96 patients (out of 133 who fulfilled the inclusion criteria) were assessed and allocated into three groups: group A (n = 24), ART-naïve; group B1 (n = 37), treated with non-protease-inhibitor (PI) containing ART; and group B2 (n = 35), treated with PI-containing ART. The prevalence of osteopenia/osteoporosis was 57/96 (59%): osteopenia 45/96 (47%) and osteoporosis 12/96 (12%). Significantly lower BMD was detected in group A (P = 0.020). Multiple logistic regression analysis showed ART to be an independent negative predictor for reduced BMD (P = 0.037; OR = 0.29, 95%CI 0.09-0.93). Vitamin D(3) deficiency was detected in 79 (82%) of the patients. The study group represented 72% of the national HIV-infected male population; this proportion being higher than in any other study reported to date. The prevalence of reduced BMD was notably higher than the national prevalence among men of comparable age. There was no association between reduced BMD and any specific ART. According to our results, absence of ART was confirmed as an independent predictor of osteopenia/osteoporosis. Targeted screening and early treatment present a reasonable strategy for preventing reduced BMD in HIV-infected patients, but correcting vitamin D(3) levels could also be an important component.