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The Middle East and North Africa (MENA) region continues to be perceived as a region with very limited HIV epidemiological data, raising many controversies about the status of the epidemic in this part of the world. The objective of this review and synthesis was to address the dearth of strategic interpretable data on HIV in MENA by delineating a data-driven overview of HIV epidemiology in this region.A comprehensive systematic review of HIV, sexually transmitted infections (STIs) and risk behavior studies in MENA, irrespective of design, was undertaken. Sources of data included Medline for peer-reviewed publications, Google Scholar for other scientific literature published in nonindexed local and regional journals, international organizations reports and databases, country-level reports and database including governmental and nongovernmental organizations publications, as well as various other institutional documents.Over 5000 sources of data related to HIV and STIs were identified and reviewed. The quality of data and nature of study designs varied substantially. There was no evidence for a sustainable HIV epidemic in the general population in any of the MENA countries, except possibly for southern Sudan. The general pattern in different countries in MENA points towards emerging epidemics in high-risk populations including injecting drug users, men who have sex with men (MSM) and to a lesser extent female sex workers, with heterogeneity between countries on the relative role of each of these high-risk groups. Exogenous HIV exposures among nationals linked to travel abroad appeared to be the dominant HIV transmission pattern in a few MENA countries with no evidence for much epidemic or endemic transmission. The role of bridging populations in bridging the HIV infection to the general population was found to be very limited.Although they do not provide complete protection against HIV spread, near universal male circumcision and possibly the prevailing sexually conservative cultural norms seemed to have played so far a protective role in slowing and limiting HIV transmission in MENA relative to other regions. If the existing social and epidemiological context remains largely the same, HIV epidemic transmission is likely to remain confined to high-risk populations and their sexual partners, in addition to exogenous exposures. HIV prevention efforts in this region, which continue to be stymied by stigma associated with HIV/AIDS and related risk behaviors, need to be aggressively expanded with a focus on controlling HIV spread along the contours of risk and vulnerability. There is still a window of opportunity to control further HIV transmission among high-risk groups in MENA that, if missed, may entail a health and socioeconomic burden that the region, in large part, is unprepared for.