he feature articles in this issue of BETA offer a prismatic look at treatment issues that may particularly concern people who have been living with HIV and taking antiretroviral treatments for some time. Fatigue is a common side effect of both HIV itself and antiretroviral treatment, and is common in people with more advanced HIV disease. See "HIV-Related Fatigue".

"Dual Protease Inhibitors Gain Ground" explores an increasingly popular approach to protease inhibitors (PIs), namely, using small doses of ritonavir (Norvir) in combination with other PIs to achieve a regimen that is theoretically more potent and also easier to take. With Kaletra (lopinavir/ritonavir) as a focal point, Dave Gilden discusses the background and rationale for boosted or dual PIs. So far, Kaletra looks promising for people with HIV who have already exhausted a number of antiretroviral options, and shows efficacy even in people with PI resistance.

Another angle on the issue of long-term antiretroviral therapy and adverse effects is what role the U.S. Food and Drug Administration (FDA) plays or might play to anticipate and manage drug side effects—basically, to safeguard consumers. Many drugs for HIV were approved rapidly through an accelerated approval mechanism for which many HIV activists lobbied, so as to provide access to potentially life-saving drugs to people with no other treatment options. Yet subsequent developments, such as the continued emergence of long-term side effects (e.g., so-called lipodystrophy) that are at least in part related to treatment, have caused many to reevaluate the best way to speedily yet safely allow drugs to be placed on the market. Reinvigorating or enforcing a tool already in place, the so-called Phase IV of clinical testing, might be one approach (see "Monitoring Anti-HIV Medicines: What Is the FDA’s Role?").

Also in this issue are our regular departments. This edition of Conference Coverage features a comprehensive look at the encouraging variety of anti-HIV medications in the pipeline, as presented a few months ago in Chicago at the 8th Conference on Retroviruses and Opportunistic Infections (CROI), which has become the preeminent annual science conference for HIV/AIDS.

In the Global Epidemic, we profile Botswana in order to provide a perspective on HIV-related news and effects from a region that is highly impacted by HIV. In fact, Botswana is the country with the highest seroprevalence rate in the world: prevalence among adults is estimated to be 35.8%, and increasing. It is hard not to use the word "staggering" when describing the situation in Botswana. Yet many admirable efforts are underway to combat HIV from a number of directions, no small feat in a country where, despite attempts to better educate all children, illiteracy and a large rural population—among other factors—complicate HIV treatment and prevention efforts.