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Background: The global diversity of HIV forms a major challenge to the development of an HIV vaccine, as well as diagnostic, drug resistance, and viral load assays, which are essential to reaching the UNAIDS 90:90:90 targets. We sought to determine country-level HIV-1 diversity globally during 1990-2015.Methods: We assembled a global HIV-1 molecular epidemiology database through a systematic literature search and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. We collected additional unpublished data through a global survey of experts. Prevalence studies with original HIV-1 subtyping data collected during 1990-2015 were included. This resulted in a database with 383 519 subtyped HIV-1 samples from 116 countries over four time periods (1990-99, 2000-04, 2005-09 and 2010-15). We analysed country-specific numbers of distinct HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in each time period. We also analysed country-specific proportions of infections due to HIV-1 recombinants, CRFs, and URFs and calculated the Shannon Diversity Index for each country. Finally, we analysed global temporal trends in each of these measures of HIV-1 diversity.Results: We found extremely wide variation in complexity of country-level HIV diversity around the world. Central African countries such as Chad, Democratic Republic of the Congo, Angola and Republic of the Congo have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe (Spain and France) and North America (USA) (up to 39 distinct HIV-1 variants in Spain). The proportion of HIV-1 infections due to recombinants was highest in South-East Asia (>95% of infections in Viet Nam, Cambodia, and Thailand), China and West and Central Africa, mainly due to high proportions of CRF01_AE and CRF02_AG. Other CRFs played major roles (>75% of HIV-1 infections) in Estonia (CRF06_cpx), Iran (CRF35_AD), and Algeria (CRF06_cpx). The highest proportions of URFs (>30%) were found in Myanmar, Republic of the Congo and Argentina. Global temporal analysis showed consistent increases over time in country-level numbers of distinct HIV-1 variants and proportions of CRFs and URFs, leading to increases in country-level HIV-1 diversity.Conclusion: Our study provides epidemiological evidence that the HIV pandemic is diversifying at country-level and highlights the increasing challenge to prevention and treatment efforts. HIV-1 molecular epidemiological surveillance needs to be continued and improved.IMPORTANCE Global HIV diversity forms a major challenge to the development of an HIV vaccine, as well as diagnostic, drug resistance, and viral load assays, which are essential to reaching the UNAIDS 90:90:90 targets. This is the first study to analyse global country-level HIV-1 diversity during 1990-2015. We found extremely wide variation in complexity of country-level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East Asia, China and West and Central Africa. The highest proportions of URFs were found in Myanmar, Republic of the Congo and Argentina. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country-level and highlights the increasing challenge to HIV vaccine development, and diagnostic, drug resistance, and viral load assays.