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Experts Debate Broad Drug Prophylaxis Policy for HIV Infected in Africa
Every year, opportunistic infections wreak havoc on hundreds of thousands of African people weakened by HIV, sapping the continent of productive labor and drastically reducing life expectancies. As one approach to combating this staggering problem, officials with the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) recently finalized a policy statement recommending that the antibiotic cotrimoxazole be provided on a daily basis to HIV-infected individuals throughout Africa to ward off secondary infections.
While this strategy is being heralded in much of Africa, some researchers are sounding a note of caution, suggesting that further testing may be required to ensure that the program will not undermine several frontline antibiotic and antiparasitic drugs used in some parts of the continent. Researchers and officials discussed the potential impacts of the prophylaxis strategy during a symposium at the 49th annual meeting of the American Society for Tropical Health and Medicine (ASTMH).
Cotrimoxazole, also known as trimethoprim-sulfamethoxazole (TS) and sold in the U.S. under trade names such as Bactrim and Septra, is widely used in developing nations. At $8 to $17 per person per year, costs of providing this drug to HIV-infected populations falls within the reach of many African health ministries, say proponents of the prophylaxis strategy, particularly if bulk buying and funding support programs are implemented.
Proponents describe a desperate need for implementing this strategy. Throughout sub-Saharan Africa where the AIDS epidemic rages, "there is no hope, there is no cure, there is no medicine given to these people," declares UNAIDS advisor Badara Samb. "One of our big efforts next year will be the promotion of cortimoxazole use throughout Africa." The strategy also has support from the U.S. Centers for Disease Control and Prevention, Doctors Without Borders, AIDS activist groups, and numerous HIV/AIDS experts. "The main attraction of cotrimoxazole [prophylaxis] is that it's something that can be done now," says Christopher Plowe, a malaria researcher with the Center for Vaccine Development at the University of Maryland. "It's a generic drug, it's cheap, it's available, and it could be started immediately."
Assuming the prophlaxis strategy is implemented throughout Africa, the small numbers of HIV-infected individuals who actually receive TS treatments could temper its effects. Experts contend that only about 1% of HIV-infected Africans will learn that they are infected with this virus and thus will seek treatment. "People prefer not to know their HIV status," Samb says, explaining that many consider such knowledge the equivalent of a death sentence. However, the prophylaxis strategy could help to change that attitude, he says.
The impetus for adopting the prophylaxis strategy throughout Africa stems from two studies conducted in Abidjan, Cote d'Ivoire, and published in The Lancet in 1999. According to those studies, routinely administering this drug to HIV-infected individuals significantly reduces bouts with severe illnesses, hospitalizations, and numbers of deaths from opportunistic infections among this population group. Based mainly on these findings, health ministers of Cote d'Ivoire and Senegal instituted cotrimoxazole prophylaxis in their respective countries. Gabon subsequently initiated a similar strategy on a somewhat less formal basis, and South Africa officials are planning to follow suit. UNAIDS is keen to encourage this process in other African nations.
Some researchers worry that cotrimoxazole prophylaxis may not work as well in some regions as others, and may even lead to doing more harm than good in those regions. They urge that further efficacy studies be undertaken in central and eastern African nations where the spectrum of drug resistance and the arsenal of frontline antimicrobials differ significantly from Cote d'Ivoire.
"The [African] continent is so big and so diverse with varying spectra of pathogens and resistance to TS, it's difficult to transfer recommendations that may be applicable in Cote d'Ivoire to areas of East Africa," says James Kublin, a malaria researcher with the University of Malawi. Salmonella and Streptococcus pneumoniae are more sensitive to TS in Cote d'Ivoire than in eastern Africa, he notes. Moreover, nontyphoid Salmonella are more prevalent in Cote d'Ivoire than in many of the central and eastern nations where enteric gram-negative bacteria and Staphylococcus aureus infections occur more frequently. In Malawi, enteric bacteria and S. pneumoniae isolates show almost 90% resistance to cotrimoxazole, he adds.
In addition, TS targets the same enzymes as pyrimethamine-sulfadoxine, or Fansidar, which is now the principal malaria drug in several countries including Malawi, South Africa, Kenya, and Tanzania, where rampant resistance to chloraquine has rendered that drug essentially useless, Kublin notes. There, widespread cotrimoxazole prophylaxis could shorten the useful life of important treatments for bacterial and parasitic infections in areas with already high background levels of resistance, he says.
Recognizing these risks, UNAIDS calls for surveillance and monitoring systems to screen for increased drug resistance where prophylaxis is used. However, resistance at the population level is less of an issue than are potential drug failures at the individual level, says Plowe. "What concerns us more in countries like Malawi [is] a person who is taking cotrimoxazole every day who then gets malaria and the only [antiparasitic] drug available is Fansidar, then this cross-resistance will affect [the efficacy of] Fansidar and that person may fail treatment and get severe disease," he says. Although the prophylaxis strategy should go forward, he says, "what we feel strongly about is that efficacy studies should be done in some areas."
However, while the WHO/UNAIDS policy statement supports monitoring, it contains no language recommending additional efficacy trials. "This is a drug that has proven effective in preventing opportunistic infections in at least two major studies," Samb says. "For those 30 million people living with HIV/AIDS who have nothing to prolong their lives, nothing to improve their quality of life, I don't think it is wise waiting [any longer] to provide them [with] a medicine that we know may have some beneficial effects for them." Moreover, three other efficacy studies that had been under way in Senegal, South Africa, and Malawi either were discontinued or dropped the placebo arm after the Cote d'Ivoire data were released because lead investigators considered it unethical to continue them under their original designs.
"I think it was reasonable to discontinue the studies where the environment was similar to that of Abidjan," Kublin says. "But in other areas, given the resource-poor settings, validation of efficacy seems warranted if a country is to devote its resources to such a widespread effort, especially if there is doubt regarding the efficacy and public health repercussions of such an intervention."
Christine Stencel
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