AIDS Read 13(1):5-6, 2003. © 2003 Cliggott Publishing, Division of SCP Communications

Witness another World AIDS Day, December 1, 2002, the 15th annual recognition of this subject, with a commentary in The Lancet for that week arguing that failure to prevent and treat HIV/AIDS globally is a "crime against humanity."^[1] The theme this year is "Live and Let Live: Ending Stigma and Discrimination." However, as shown in Figure 1, although accounting for only 14.7% of the world's population, Africa and the Middle East have 72.5% of all cases of HIV infection, with but a few thousand persons currently receiving antiretroviral therapy. In addition, almost two thirds of the world's population reside in Asia and the Pacific region, areas considered by many epidemiologists to be sites of the next major explosion of HIV disease. By 2010, the US National Intelligence Council estimates that more than 75 million persons could be infected in only 5 "next-wave" countries: Russia, India, China, Nigeria, and Ethiopia.^[1]

Figure 1. Comparison of the global population distribution (left) and the distribution of HIV/AIDS (right). (Data derived from UNAIDS Global Report. June 2002.)

In a special session of the United Nations, held from June 25 to 27, 2001, access to medications was recognized as one of the fundamental elements ensuring the innate right of all persons to enjoy the highest attainable standard of health. The prevention and treatment of HIV/AIDS were emphasized as "mutually reinforcing elements" of an effective health response.^[1] Yet, of the 43 million people currently living with HIV/AIDS, fewer than 1 million have access to and are treated with antiretrovirals.^[2] That fact has become part of a new public service campaign to increase awareness of this issue in the United States (Figure 2).

Figure 2. Increasing awareness of the global disparity in antiretroviral treatment of HIV/AIDS. Designer Kenneth Cole is seen holding a typical billboard, along with actor and AIDS activist Richard Gere and amfAR cochair Dr Mathilde Krim. (Public service campaign initiated by Mr Cole and the American Foundation for AIDS Research [amfAR].)

The unwillingness of resource-rich nations to support the United Nations' Global Fund to Fight AIDS, Tuberculosis and Malaria is a great impediment to realization of the use of HAART worldwide. Distribution, clinical monitoring, and patient adherence are additional issues. But recent work on simplification of HAART regimens, reported at the latest Glasgow conference on HIV treatment, could have a major impact on compliance-related treatment failures in both resource-rich and resource-poor countries. For example, the Indian pharmaceutical company Cipla announced that a fixed-dose combination of stavudine, lamivudine (3TC), and nevirapine, known as Triomune, produced pharmacokinetics similar to those produced by the 3 drugs when they were given individually.^[3] This single pill needs to be taken only twice a day. (The desirability of dose-escalating nevirapine with exploration of its tolerability, particularly with regard to development of a rash, means that each drug would probably be administered separately for the first 2 weeks of initial therapy, however.) An annual regimen would cost about $350.

It is well documented that adherence rises as the complexity of a HAART regimen declines, a point emphasized by a recent comparison of the fixed-dose combination of zidovudine and 3TC (Combivir) with the 2 drugs given separately.^[4] The class of drug also appeared critical to patient adherence and to ranking on scales of patient satisfaction. For example, Maggiolo and colleagues^[5] reported a randomized, prospective study of 209 patients followed for more than 6 months with undetectable (less than 50 RNA copies/mL) viral loads while receiving 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI). Either the original therapy was continued or the PI was changed to a third NRTI (abacavir) or to a nonnucleoside reverse transcriptase inhibitor (efavirenz). During a 104-week follow-up, time to virologic failure did not differ among the 3 arms, but the continued-PI regimens failed more quickly in terms of patient tolerance, including development of lipodystrophy and hypercholesterolemia.^[5 Greater patient satisfaction -- in terms of convenience and flexibility (including dietary restrictions), side effects, and desire to continue the present regimen -- was also seen in each of 3 separate trials of 2 NRTIs given with either a PI (predominantly, indinavir or nelfinavir) or abacavir.^[6] In those studies, the PI-containing regimens all had higher daily pill counts than the other treatment protocols.

Dr Richard Pollard,^[7] in an article in the November 2002 issue of The AIDS Reader, raised the concept of simplifying adherence through once-daily dosing. However, of the 4 single-agent antiretroviral drugs that are FDA-approved for such administration, only lamivudine is being manufactured as a generic for use in resource-poor nations. References

1. Hogg R, Cahn P, Katabira ET, et al. Time to act: global apathy towards HIV/AIDS is a crime against humanity. Lancet. 2002;360:1710-1711.
2. Accelerating access to treatment and care. Fact Sheet UNAIDS, 2002. Available at: http://www.unaids.org/barcelona/presskit/factsheet/FSaccess_en.htm. Accessed December 5, 2002.
3. Gogtay JA, Manek V, Nayak VG, et al. A pharmacokinetic evaluation of lamivudine, stavudine, and nevirapine given as a fixed dose combination pill versus the same drugs given separately in healthy human volunteers. In: Program and abstracts of the 6th International Congress on Drug Therapy in HIV Infection; November 17-21, 2002; Glasgow, UK. Abstract PL8.4.
4. Jordan J, Delea T, Sherrill B, et al. Impact of fixed-dose combination zidovudine/lamivudine on adherence to antiretroviral therapy: a retrospective claims-based cohort study. In: Program and abstracts of the 6th International Congress on Drug Therapy in HIV Infection; November 17-21, 2002; Glasgow, UK. Abstract P97.
5. Maggiolo F, Callegaro A, Ripamonti D, et al. 104 Weeks outcome of simplified regimens in PI-experienced patients. In: Program and abstracts of the 6th International Congress on Drug Therapy in HIV Infection; November 17-21, 2002; Glasgow, UK. Abstract PL6.2.
6. Jordan J, Cahn P, Goebel F, et al. Abacavir containing regimens lead to greater patient satisfaction than protease inhibitor containing regimens. In: Program and abstracts of the 6th International Congress on Drug Therapy in HIV Infection; November 17-21, 2002; Glasgow, UK. Abstract P98.
7. Pollard RB. Can HIV infection be treated successfully with a once-daily regimen? AIDS Reader. 2002;12:489-500, 508.