AIDS: Are We Doing Enough?
Authors: Inder M. Verma
Journal: Molecular Therapy (2000)

The news is bad—in fact, very bad for sub-Saharan Africa. Since the early 1980s, HIV has spread throughout sub-Saharan countries. The prevalence in adults (15–49 years) now tops nearly 20%. Worldwide over 35 million people are living with AIDS, 25 million in Africa alone. What is devastating and immeasurable is the loss of a very virile and economically essential population—a whole generation is being lost. Sadly, while statistics pile up, even preventable transmission of HIV from infected pregnant mothers to newborns is not being practiced. In South Africa alone the prevalence of disease zoomed in pregnant women from less than 1% to over 20%, just in the past decade. By some estimates, over 40 million children in Africa alone will be orphans by the year 2020. What is being done to combat this scourge? The first wave of pharmaceutical drugs was designed to prevent virus replication, specifically in the form of agents that blocked reverse transcriptase and protease. Administration of a mixture of three such antiviral compounds, popularly known as HAART, can lead to significant reduction of the viral load in patients. The length of the response remains a concern, considering the emergence of variant strains of HIV-1 that are resistant to combination drug therapy. Furthermore, even a short cessation of this rigorous regimen of drugs leads to virus reemergence. Not surprisingly, substantial efforts are being employed to develop alternative genetic approaches to combat and subdue virus replication. These include soluble receptors (CD4), Tat and Rev decoys, transdominant Tat and Rev, antisense oligonucleotides and ribozymes to Tat/Rev nexus, single-chain antibodies, transdominant gag, and even toxic genes to self-induce HIV target cells. However, all of these approaches require an efficient delivery system. Retroviral vectors harboring a transdominant negative REV protein (Rev M-10) have been used in humans infected with HIV. These initial studies demonstrated that cells transduced with Rev M-10 recombinant virus had a significantly longer half-life than control cells when reinfused in patients at different stages of the disease. Similarly, T cells from rhesus macaques upon transduction with antisense constructs of Tat and Rev genes of SIV lowered virus load upon challenge with Simian AIDS viruses. This is exciting because gene therapy can contribute to combating AIDS. In fact, transduction by lentivirus vectors may be more efficacious since they can deliver the modified Tat/Rev molecules to even resting T cells and macrophages. It will be ironic if lentiviral vectors will combat lentivirus spread. After all, diamond cuts diamond! However, we must return to the harsh reality of Africa and Southeast Asia, where the disease is rampant but the resources are scarce. In many countries the average health-related expenses allocated by the government are less than $1/year/inhabitant. Remember, one billion people in this world live on $1/day and another two billion on $2/day. Clearly the high expenses of combination drug therapy (well over $1000/year/patient) and surely gene therapy approaches to reduce the burden of AIDS for a vast majority of humanity are unfeasible. Realistically, education, political will, and vaccines are the only alternatives. The decline in AIDS infection in countries like Uganda, Senegal, and Thailand is a direct result of both education and the political will of their leaders. We must find ways to educate middle-school children about the dangers of AIDS—by high school it may be too late. The international community of scientists has formed many alliances with a number of African and Asian countries to test vaccines on high-risk groups. This is the only way in the long run if AIDS is to become a distant memory like small pox. Where there is a will there is a way!