Search

Objectives: To analyze phylogenetic relations and assess the role of cross-border clusters in the spread of HIV-1 subtype B across the Balkans, given the general trends of new HIV diagnoses in seven Balkan countries., Design: Retrospective phylogenetic and trend analysis., Methods: In-depth phylogenetic, phylodynamic and phylogeographic analysis performed on 2415 HIV-1 subtype B sequences from 1999 to 2019 using maximal likelihood and Bayesian methods. The joinpoint regression analysis of new HIV diagnoses by country and modes of transmission using 2004-2019 ECDC data., Results: Ninety-three HIV-1 Subtype B transmission clusters (68% of studied sequences) were detected of which four cross-border clusters (11% of studied sequences). Phylodynamic analysis showed activity of cross-border clusters up until the mid-2000s, with a subsequent stationary growth phase. Phylogeography analyses revealed reciprocal spread patterns between Serbia, Slovenia and Montenegro and several introductions to Romania from these countries and Croatia. The joinpoint analysis revealed a reduction in new HIV diagnoses in Romania, Greece and Slovenia, whereas an increase in Serbia, Bulgaria, Croatia and Montenegro, predominantly among MSM., Conclusion: Differing trends of new HIV diagnoses in the Balkans mirror differences in preventive policies implemented in participating countries. Regional spread of HIV within the countries of former Yugoslavia has continued to play an important role even after country break-up, whereas the spread of subtype B through multiple introductions to Romania suggested the changing pattern of travel and migration linked to European integration of Balkan countries in the early 2000s., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl., Design: Cohort study based on routinely collected data from the HIV-CAUSAL collaboration., Methods: For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics., Results: In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2)., Conclusion: Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.

Background: The rate of transmitted drug resistance (TDR) may increase with wider use of antiretroviral therapy and can contribute to therapeutic failure. We analysed time trends in TDR among HIV seroconverters., Methods: Using CASCADE data of individuals with well estimated dates of HIV seroconversion, we examined HIV nucleotide sequences collected prior to antiretroviral therapy use from 1996-2012. All samples were taken within 12 months of testing HIV positive. Using logistic regression, we examined the association between TDR and year of seroconversion, adjusting for confounders., Results: Of 4717 individuals seroconverting between 1996 and 2012, median (IQR) age at seroconversion was 33 (27, 39) years. The majority (3839; 92%) were male, mainly exposed through MSM (3767; 80%), and infected with subtype B (3464; 73%). Overall, 515 (11%) individuals had at least one drug resistance-related mutation; 280 individuals with nucleoside reverse transcriptase, 185 with nonnucleoside reverse transcriptase, and 144 with protease inhibitor mutations. Estimated TDR prevalence was 19.4% (8.2, 36.0) in 1996, significantly decreasing to 8.5% (5.9, 11.9) in 2012 [odds ratio (OR; 95% confidence interval (CI)) = 0.92 (0.90, 0.95) per year increase]. Individuals exposed through sex between men and women were significantly less likely to have been infected with a drug-resistant strain [OR (95% CI) = 0.59 (0.41, 0.87) compared with MSM], and there was marginal evidence that sampling during acute infection was associated with higher odds of resistance [OR (95% CI) = 1.20 (0.97, 1.7), P = 0.093] compared with later sampling., Conclusion: TDR has decreased over calendar time although a significant proportion of new infections still carry resistance-related mutations.

Objective: Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient., Design: Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID., Method: We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID., Results: In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post-first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective., Conclusion: As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.