Available data indicate that HIV prevalence in the general population is at very low levels of much less than 1% in all MENA countries apart from Djibouti, Somalia, and Sudan (Table 3). In Djibouti, HIV prevalence was reported to be around 3% nationally among ANC attendees and among blood donors [188,189,191]. Lower rates were observed of about 1% in Somalia, although in one setting, it was at 2.7% among pregnant women . Southern Sudan is of particular concern and could be already in a state of general population HIV epidemic, although conclusive evidence is still lacking. Rates of as low as 0% and as high as 11% have been reported at various locations among ANC attendees and blood donors in southern Sudan [244,245].
Sexual behavioral data among the general population in MENA remain rather limited, with, to our knowledge, no nationwide sexual behavior survey being ever conducted in the region. However, available data from several small-scale investigations indicate that sexual risk behaviors are present but relatively at low levels compared to other regions . Multiple partnerships, premarital and extramarital relationships, casual sex, and contact with FSWs are reported in most countries but with significant variations . Youth appear to engage to some extent in sexual risk behavior but not at levels seen in other regions . Although polygamy is common in MENA, it appears to be in decline with estimates usually ranging between 3 to less than 20% [14,137,229,257–260]. However, nonconventional forms of spousal relationships have been increasingly emerging in MENA such as zawaj al-muta'a (temporary marriage), zawaj urfi (clandestine marriage), and zawaj al misyar (travelers' marriage) . These nonconventional types of marriage possibly could be perceived as legitimization of premarital and extramarital sex and may be increasing the risk of STI transmission among those involved in such marriages [2,261].
Contrary to widely held perception of very limited data, there is a considerable amount of epidemiological data on HIV in MENA. Nevertheless, data are fragmented, lack integration, and are amorphous. The nature of evidence is best exemplified by shattered glass. Numerous studies and point-prevalence surveys are distributed among different disciplines and stakeholders at the local, national, and regional level with no coherent integration, synthesis, and analysis. As part of the systematic search, we have identified hundreds of studies, databases, focused assessments, and reviews that have never been published in scientific publications nor are easily or widely accessible. A large amount of data and studies continue to be disseminated within small circles at the national and regional levels in the form of confidential and nonconfidential reports and unpublished data.
However, the large sums of available data are not necessarily representative and are often not collected using standard accepted surveillance methodologies. A large fraction of data originates from facility-based surveillance on convenient samples of the population. It is often not clear whether internationally accepted ethical guidelines for research on humans were strictly followed in the conduct of studies. Generally speaking, HIV epidemiologic evidence in MENA is highly heterogeneous in terms of quality but, overall, of limited quality. Fortunately, the quality of data has been steadily improving in recent years, although the availability of data and HIV research capacity vary substantially from one country to another. Iran and Morroco, despite many limitations, continue to be a regional leaders in HIV research and HIV/AIDS response, with several countries such as Pakistan and Sudan catching up in building their capacity within the last few years.
Despite the limitations of available data, the diverse sources of data were consistent on the overall epidemiologic picture delineated in this article. There is no evidence for an HIV epidemic in the general population in any of the MENA countries, except possibly for southern Sudan . It is worth noting that south Sudan has sociocultural attributes that are distinct from the rest of MENA countries and the epidemic in this subregion is probably best understood in terms of the context of HIV epidemiology in neighboring sub-Saharan countries such as Kenya and Uganda.
The general pattern in MENA countries points toward growing epidemics in high-risk populations including IDUs, MSM, and, to a lesser extent, FSWs . Table 4 summarizes the current status of the HIV epidemic in MENA countries based on the available and synthesized evidence. The limitations of the surveillance systems in MENA and the scarcity of reliable data are manifest as the status of the epidemic remains unknown in the majority of the risk groups for each country. This testifies to the heterogeneity of available evidence in the region.
Commercial heterosexual sex networks seem to be the major drivers of substantial HIV transmission only in Djibouti, Somalia, and Sudan due to the large size of the commercial sex networks in these settings and to the high levels of risk behavior practiced in these networks. Similar heterogeneities apply to the rest of high-risk groups. Whereas injecting drug use is large in scale in Iran and Pakistan and continues to be the major driver of the HIV epidemics in these countries, it appears to be smaller in scale and have a minor role in other MENA countries. The nature and levels of HIV spread among MSM remains, in relative terms, the least understood in MENA.
As can be seen from the description of HIV epidemiology in high-risk groups, there is substantial heterogeneity in HIV spread across MENA, and different risk contexts are present throughout the region. However, the HIV epidemic in MENA can be coarsely classified into two groups based on the extent of HIV spread. The first is the group of somewhat considerable HIV prevalence, which includes the three countries Djibouti, Somalia, and Sudan (mainly southern Sudan). The second group, labeled here as Core MENA Region, is the group of more limited HIV prevalence, which includes the rest of MENA countries. As the latter group consists of most MENA countries, HIV epidemiology here represents the main dynamics found in MENA.
The second pattern of HIV epidemiology in Core MENA Region is that of concentrated HIV epidemics among some of the high-risk groups (HIV prevalence consistently exceeding 5%). There is already documented evidence for concentrated epidemics among IDUs  and suggestive evidence for concentrated epidemics among MSM in some countries such as Egypt , Sudan (north Sudan) , and Pakistan [81–83]. There is no evidence for concentrated HIV epidemics, at the country level, among FSWs in Core MENA Region countries.
Djibouti, Somalia and southern Sudan stand out from the Core MENA Region as having a state, or near state, of generalized HIV epidemics. Yet, most infections in these countries seem to be concentrated in high risk groups and bridging populations, more specifically in commercial heterosexual sex networks (Fig. 1) . There is no evidence of sustainable general population epidemic in these countries (apart from possibly southern Sudan); however the size of the commercial heterosexual networks in these settings is large enough to support an epidemic with a prevalence exceeding 1% in the population as a whole .
Several protective factors appear to have slowed and limited HIV transmission in MENA relative to other regions. A key factor is male circumcision, which has an established 60% efficacy against HIV heterosexual acquisition [263–265]. Male circumcision is nearly universal in MENA . Southern Sudan is the only part of MENA where this practice is not the norm . This could be partially contributing to the considerable spread of HIV in southern Sudan relative to the rest of MENA. The extensive coverage of male circumcision in MENA suggests limited potential for a sustainable HIV epidemic in the general population .
The influence of Islamic cultural traditions on the cultural and social traditions of MENA is another possible limiting factor to the spread of HIV in this region. Although from the available literature, one cannot definitely conclude that Islamic cultural traditions have reduced HIV transmission in the region, several observations, including some quantitative studies, support the protective role of Islamic cultural traditions. Being a Muslim has been repeatedly associated with lower risk behavior [269–274] and lower HIV prevalence [4,270,275–283], in both Muslim-majority countries as well as in Muslim minorities in predominantly non-Muslim nations [4,284]. Islamic cultural traditions have been cited as a protective factor even after adjustment for male circumcision . In fact, in addition to requiring male circumcision, Islam promotes a line of behavior that is in concordance with several themes of HIV/AIDS prevention including prohibitions against premarital and extramarital sex , prohibitions against alcohol consumption with alcohol's strong association with higher risk behavior [278,287,288], closed sexual networks of monogamous or polygamous marriages , among others. It is worth noting though that, despite being heavily influenced by Islamic traditions, parts of the region are experiencing a sociocultural transition at varying pace that is leading to more tolerance and acceptance of practices such as premarital sex and extramarital sex . Counting only on the ‘cultural immunity’ of religious and traditional mores  is, therefore, not enough to prevent an HIV epidemic in the region.
A key highlight of HIV epidemiology in MENA is that of the vulnerability of spouses and sexual partners of high-risk group members. Women are especially vulnerable, as most high-risk behaviors in MENA are practiced by men and the majority of infected women acquired the infection through their husbands or sexual partners. For example, 97% of HIV-infected women in Saudi Arabia acquired the infection from their husbands . Similarly, in Iran, 76% of HIV-infected women acquired the infection from their husbands who were predominantly IDUs [291,292]. Also, there appears to be a substantial gap in age in sexual partnerships between men and women in MENA, with women marrying older men. Intergenerational sex puts women at even higher risk of exposure to STI infections, including HIV .
Women who are sexual partners of high-risk group members appear to rarely engage in risk behavior and probably seldom bridge the infection to the rest of the population apart from occasionally to their own children through vertical transmission. Their limited role in HIV transmission dynamics could also be one of the factors behind the consistently very low HIV prevalence in the general population in MENA.
The low HIV prevalence observed in some risk groups in MENA should not be interpreted necessarily as lack of HIV epidemic potential. The extreme within-country variation observed in the prevalence of HIV among different population samples is an indication of existing hidden subepidemics or potential epidemics in certain settings within any one country. Also, the heterogeneity in the availability of well designed studies across population groups and countries could be preventing the identification of hidden epidemics among some hard-to-reach high-risk populations.
The moderate to high prevalence of some proxy biological markers of risk behavior in MENA is another indicator of HIV potential in certain risk groups. For example, hepatitis C infection, which shares the parenteral mode of transmission with HIV, has been documented to be at moderate to high levels among IDUs in most MENA countries  compared to those reported in other regions . Recent rapidly growing HIV epidemics documented among IDUs in Pakistan [76,78,85,295], following many years of low HIV prevalence [41,75,77,296,297] affirms the epidemic potential for at least some of the MENA IDU populations. Similarly, HIV prevalence among hijras in one study in Pakistan was 0.0% in 1998, but syphilis prevalence was 37% [89,298]. This suggests substantial levels of sexual risk behavior and potential for HIV infectious spread in the event HIV is introduced into sexual networks involving this population. This seems to have been confirmed as recent data have shown some rapidly rising epidemics among MSWs and hijras in Pakistan [81–83]. There is also a pattern of increasing HIV prevalence among MSM in other regions with similar socio-cultural background to MENA countries such as in Indonesia in south-east Asia [299,300].
Apart from Djibouti, Somalia, and southern Sudan, the apparently lower levels of risk behavior among FSWs in MENA, in addition to the proven biological efficacy of male circumcision against HIV acquisition with its nearly universal coverage in this region, suggest a limited potential for massive or even concentrated HIV epidemics among FSWs in MENA . This, in turn, limits the role that bridging populations (mainly clients and partners of FSWs and sexual partners of IDUs and MSM) may play in HIV transmission in MENA. As pointed out earlier, a key characteristic of sexual partners of high-risk group members (mainly women) in this region is their vulnerability to HIV, rather than their role in HIV transmission dynamics. With all these factors interplaying, and if the existing social and epidemiological context in the region remains largely the same, it seems unlikely that the MENA region will experience a sustainable HIV epidemic in the general population in at least the foreseeable future, if ever. However, increasing economic pressures affecting, in particular, the large population of young people and ongoing political instability may lead to a rise in risk behavior practices and consequently HIV transmission. In a worst case scenario, the region may face up to a few percentage points prevalence in a few of its countries.
Although HIV prevalence levels in MENA are among the lowest globally, the nature of HIV epidemiology in MENA is no exception to HIV epidemiology in every other region apart from sub-Saharan Africa. HIV in MENA travels along the indigenous contours of risk and vulnerability just as in every other region. The HIV epidemic has not yet reached its epidemic potential in this region and there is an opportunity for prevention that should not be missed to control the epidemic . Missing this window of opportunity may entail a health and socioeconomic cost that the region, in large part, is unprepared for. Stigma associated with HIV/AIDS remains one of the major contributors for the region's unpreparedness to tackle the epidemic and a key barrier towards rational evidence-based policymaking.
The analytical insights drawn from this synthesis of thousands of studies and data sources indicate that there is no escape from the necessity of expanding scientific research on HIV in MENA to address the gaps in our knowledge of the status of the epidemic in different risk groups as manifested in Table 4. In particular, robust surveillance systems need to be developed to monitor HIV transmission, especially among high-risk groups. Effective surveillance of most at-risk populations is essential to detect emerging epidemics at an early stage. This would facilitate targeted prevention at an early phase of an epidemic. Monitoring recent infections and examining the nature of exposures could also be useful in detecting emerging endemic chains of transmission within MENA populations.
Despite many limitations, there is increasingly a political feasibility for implanting and scaling up of interventions including those among high-risk groups . However, current efforts in MENA continue to be focused on awareness-raising activities among the general population, which is the group at the lowest risk of HIV infection. Resources need to be prioritized for interventions among those most at risk, irrespective of whether these groups are ‘culturally safe’ or not [13,303]. Developing creative mechanisms for working with high-risk groups, even if discreetly, need to be explored. A successful formula for HIV efforts could be government organized nongovernmental organizations (GONGOs), where governments fund and support NGOs to discreetly provide services to high-risk populations. NGOs may enable governments to deal with high-risk groups indirectly, thereby avoiding political or cultural sensitivities in explicit outreach efforts among hidden and stigmatized populations [304,305].
Although countries need to address the structural factors that drive risk of exposure to HIV, the priority should be on addressing the direct factors that put individuals at risk of HIV exposure, as tackling structural factors takes time and is beyond the control of the public health community . Access to testing, care, and treatment services need to be expanded substantially. Prevention efforts need to capitalize on the strengths represented by cultural traditions, and be culturally sensitive, while fostering effective responses to the epidemic [1,307,308]. One of the countries in the region, Iran, is already a world leader in harm reduction and has paved the way by showing how HIV prevention can be implemented within the cultural fabric of MENA and in consonance with its sociocultural values.
The MENA HIV/AIDS Epidemiology Synthesis Project was funded through a joint partnership of the World Bank, the MENA Regional Support Team (RST) of United Nations Programme on HIV/AIDS (UNAIDS), and the Eastern Mediterranean Regional Office (EMRO) of the World Health Organization (WHO). LJA and GM are also grateful for the Qatar National Research Fund for supporting this work (NPRP 08–068–3–024).
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