Introduction HIV/AIDS continues to be a leading cause of alarm globally. New infections and deaths due to HIV/AIDS related complications are major issues that need to be dealt with urgently. It is particularly alarming in the sub-Saharan Africa where an average of 10% HIV prevalence in adults has been recorded. This is very high compared to the global average of 1%. The Southern Africa region accounts for about 40% of the global population living with HIV. However, the female gender is more affected by the pandemic with women and girls accounting for about 60% of this population. Although the records indicate optimistic results, there is still need to enhance the campaign. In San Francisco, the new infections and death tolls may be on a down slope but the marginalized groups are still at a risk and this needs to be addressed. In this paper the key drivers of HIV/AIDS in Southern Africa and San Francisco will be discussed. HIV/AIDS in Sub Saharan Africa The extent of the HIV/AIDS pandemic in the region can be attributed to such things as; Sexual behavior-many men and women in the region have different sex partners concurrently; these may be in cases of polygamy, small houses (side partners apart from spouse) and prostitution. Many of them do not use condoms consistently meaning that safe sex practice has not been cultivated in them (Jana et al, 13-16). Secondly, male circumcision is practiced in very low levels and as we know, male circumcision is a major boost in the prevention efforts so lack of it is on the contrary. A third driver is the stigma associated with infection. This lack of acceptance by the individual and the community forces an infected person to keep their status secret which leads to further spread of the virus. In some cases some people do not want to know their status for fear of stigmatization and this brings down the efforts of treating the infected persons. Also many sexually transmitted infections go untreated mainly due to this fear and they are a factor that encourages HIV infection. Male attitudes towards gender related issues such as reproductive health is also another contributing factor. Men do not involve themselves in such issues and therefore many of them lack the knowledge to curb the pandemic. They involve themselves in intergenerational sex, gender based violence and sexual violence. This means that the women and girls are the major victims of the men’s ignorance hence the high number of infections in females (Expert Think Tank Meeting on HIV Prevention in High-Prevalence Countries in Southern Africa 5-7 ). HIV/AIDS in San Francisco In San Francisco, the efforts of prevention and treatment have born fruits since the number of new infections and HIV/AIDs related deaths is on a downward trend. The reduction in these numbers can be highly attributed to the change of sexual behavior in heterosexual men and women and non-injecting drug users. Cases of new infections in these groups of people are very rare. However, there are still other driving forces in the spread of the disease and these include; Homosexual behavior; men who have sexual relationships with other men are at a major risk of infection. Transfemales are