The Extraordinary Hope of Antiretroviral Therapy in South Africa. Part 2
Coinfection with M. tuberculosis and HHV-8 are common in the developing world—in sub-Saharan Africa, in particular—and manifestations of these coinfections (tuberculosis [TB] and Kaposi sarcoma [KS], respectively) could complicate application of ART in these areas of the world. HIV-infected patients in the developing world tend to present with HIV very late during the course of the disease, usually with active OIs. TB is, by far, the most common OI. TB leads to significant nutritional wasting and will cause both specific and nonspecific activation in the immune system, which might lead to an increase in viral load and further impair both HIV suppression and immunologic recovery. Some clinicians have wondered whether patients with active TB or KS would be “just too sick” to benefit from triple combination ART or whether combination therapies for both HIV and these OIs would be too complex and impossible to manage effectively. Effective therapy for either TB or KS in the setting of triple combination ART may involve taking anywhere from 5 to 10 medications at any one time. The study by Cassol et al. demonstrates that patients with either of these active OIs respond well to triple combination ART utilizing a nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen.
Although the study by Cassol et al. is small, it is well done, and the results provide important insight into the short-term antiviral effects of ART in a resource-limited setting. After 90 days of therapy, almost 94% of patients with active TB had undetectable viral loads (<40 copies/mL). Eighty percent of patients with KS had undetectable viral loads by 90 days. Patients with TB had slightly greater decreases in viral load, but this is probably because the baseline viral load in patients with TB was higher than that in patients with KS. The phase I decay of virus, which occurs within the first 7 days, was rapid and comparable to the decay observed in studies in the developed world. The phase II decay was slower and more gradual, consistent with that found in previous studies of HIV treatment. Despite the generalized immune activation that can occur with TB, which almost certainly has some impact on HIV replication, triple combination ART in this setting was enormously effective. It is important to note that, in the Cassol et al. study, patients with active TB were treated with 600 mg of efavirenz. Recent studies from Thailand have indicated that responses among patients in that country who were treated with rifampicin and 600 mg of efavirenz may be adequate. These findings suggest that the pharmacokinetic interaction between efavirenz and rifampicin observed in populations in developed countries does not significantly impact the antiviral response of efavirenz-based therapy in resource-limited settings.