The reasons a medication regimen may be changed are multiple and include lack of efficacy, patient noncompliance or dissatisfaction, adverse effects, and resolution of the indication for the medication. With HIV regimens, toxicities and patient nonadherence are prominent. A study of such treatment modifications is reported by Messou et al. , an analysis of a cohort in a low-income suburb of Abidjan, Cote d'Ivoire, in a large clinic funded through a nonprofit organization with significant support from several international organizations. The authors report that toxicity is a major but by no means the sole reason for change of therapy, similar to data from other developing nations in Africa [2,3].
Toxicity associated with anti-HIV therapy dates back to its onset with the readily identified toxicities of zidovudine [macrocytic anemia, myopathy, central nervous system (CNS) disturbances]. Toxicities were increased with the recognition of metabolic disturbances especially prominent with use of protease inhibitors. Improved drug formulations, better pharmacokinetics, and development of agents with fewer adverse effects led to the current status whereby many patients are managed successfully in the developed world with once-a-day therapy. Such simpler regimens are infrequently available in the developing world where the percentages receiving any antiretroviral therapy are woefully low .
This descriptive epidemiology by Messou et al.  is from sub-Saharan Africa where live 65% of all people infected with HIV. The report is provided in a nation receiving funding from the United States government-based President's Emergency Plan for AIDS Relief (PEPFAR) as well as other prominent nongovernmental organizations (NGO) in a clinic with a remarkably low level of antiretroviral discontinuance, program efficiency, good support, and low patient costs. In settings without such organizational and international support, the results may be less satisfactory. In one Asian clinic, for example, 19% of changes were associated with issues relating to cost . In Messou's program, patients spent only about $12 per year for an entire family (mean size, 6.7), costs that pale by comparison with the estimated $200 per case spent by the Ivorian National government, and both costs pale when one considers the many additional indirect costs associated with the outbreak, such as lost productivity, lost parenting, needs of employers for retraining, and education costs for prevention which impacts the non-HIV infected.
Providing antiretroviral treatment for the very poor in the developing world will incur costs associated with improving surveillance and access as well as costs attendant with sustaining a larger infrastructure that encompasses both preventive and therapeutic goals including the increasing problems of viral resistance . A key issue is determining when cost efficacy is established, when the costs of care lessen the many indirect costs and the costs of prevention diminish future case loads .
The study reported herein describes an ideal situation, one hard to replicate in areas without prominent international funding (that constitutes much of the world) but encouraging in its findings. Accepting this fact, what were the findings in addition to cost efficiency and how are they relevant? The authors noted that the antiretroviral stavudine was particularly attendant with adverse effects and this confirms the findings of other authors . Such concerns are part of the US-based Department of Health and Human Services (DHSS) recommendations in which stavudine is not recommended for primary therapy because of toxicities including peripheral neuropathy, hepatic steatosis, and lactic acidosis . Guidelines for the developing world should as well consider relegating stavudine to secondary status as newer agents become available.
In the authors' experience efavirenz was often substituted for reasons of pregnancy, and CNS side effects were infrequent. This latter may reflect the perspicacity of Ivorian physicians in not prescribing the agent to patients with complex neurologic or psychiatric conditions. Efavirenz is unique among antiretroviral agents in its potential teratogenicity (which needs further study) but the importance of this adverse effect in potentially childbearing women cannot be underestimated .
The authors emphasize the interactions of efavirenz with antituberculous therapy. The number of individuals who die annually co-infected with Mycobacteria tuberculosis and the HIV is nearly 500 000 . The many options for co-treatment are well reviewed elsewhere . The frequency with which nevirapine was changed to an alternative therapy (and the recommended alternative efavirenz is often untenable) is worth noting.
This study represents a type of reverse translational research in which findings from the clinic, bedside, and the public health office are made evident to basic scientists in the hope that new basic discoveries show societal relevance. Good descriptive epidemiologic studies such as this one fulfill that goal and should be the incentive needed to push for the development of new forms of therapy and the dissemination of already recognized forms of therapy that are less toxic than stavudine, safer in pregnancy than efavirenz, and attendant with fewer adverse drug interactions than nevirapine.
Finally, the current study suggests that if enough funds were put into making highly-active antiretroviral therapy (HAART) available at low cost (as with the cited program), if patients were as reliant and adherent as those in this experience, then the pandemic of AIDS could begin to see some type of resolution. If the majority of HIV-infected individuals were identified, if the appropriate patients go on therapy, and if corresponding viral loads in these cases are reduced, it logically follows that transmissibility will fall and the pandemic could eventually resolve. This requires a global commitment. The global amount needed to provide preventive and therapeutic care for HIV/AIDS was estimated at over $20 billion for 2007 and appears to be growing almost exponentially. If the US expenses of over $2 billion in developmental assistance for HIV/AIDS in 2007 had been spent annually over the 8 years since the onset of military conflicts in Iraq and later Afghanistan, the expenditure of $16 billion would amount to not even 2% of the $900 billion these two wars have cost the American public. Perhaps we should redeploy our generals as epidemiologist and our soldiers as pill sharers.
1. Messou EXA, Anglaret X, Duvignace J, Konan-N'Dri E, Komena E, Gnokoro J, et al. Antiretroviral treatment changes in adults from Cote d'Ivoire: the roles of tuberculosis and pregnancy
2009 (this issue).
2. Forna F, Liechty CA, Solberg P, Asiimwe F, Were W, Mermin J, et al
. Clinical toxicity of highly active antiretroviral therapy in a home-based AIDS care program in rural Uganda. J Acquir Immune Defic Syndr 2007; 44:456–462.
3. Boulle A, Orrel C, Kaplan R, Van Cutsem G, McNally M, Hilderbrand K, et al
. Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort. Antivir Ther 2007; 12:753–760.
4. Moatti JP, N'Doye I, Hammer SM, Hale P, Kazatchkine M. Antiretroviral treatment for HIV
infection in developing countries
: an attainable new paradigm. Nat Med 2003; 9:1449–1452.
5. Kumarasamy N, Vallabhaneni S, Cecelia AJ, Yepthomi T, Balakrishnan P, Saghayam S, et al
. Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India. J Acquir Immune Defic Syndr 2006; 41:53–58.
6. Stover J, Bertozzi S, Gutierrez JP, Walker N, Stanecki KA, Greener R, et al
. The global impact of scaling up HIV
/AIDS prevention programs in low- and middle-income countries. Science (New York, NY) 2006; 311:1474–1476.
7. DHHS. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
Washington, DC: DHHS; 2008.
8. Tonwe-Gold B, Ekouevi DK, Viho I, Amani-Bosse C, Toure S, Coffie PA, et al
. Antiretroviral treatment and prevention of peripartum and postnatal HIV
transmission in West Africa: evaluation of a two-tiered approach. PLoS Med 2007; 4:e257.
9. Donald PR, van Helden PD. The global burden of tuberculosis-combating drug resistance in difficult times. N Engl J Med 2009; 360:2393–2395.
10. CDC, DHHS. Guidelines of prevention and treatment of opportunistic infections in HIV-infected adults and adolescents.
Washington, DC: DHHS; 2008.