The Extraordinary Hope of Antiretroviral Therapy in South Africa. Part 3
The increased CD4+ cell count in patients with active TB was relatively greater than that in patients with KS, possibly because patients with TB have a larger, more dynamic population of highly productive CD4+ cells. For both cohorts, the increase in CD4+ cell counts was greatest during the first 7 days of treatment, a finding consistent with those from studies of HIV therapy in the developed world. These findings, together with other studies, strongly suggest that treatment of HIV-1 subtype C results in significant virologic and immunologic benefit, even in the setting of active OIs and low CD4+ cell counts. The long-term effects of ART in the resource-limited setting will need to confirmed by continued follow-up of the patients in the Cassol et al. study and by other ongoing studies. Further research is needed on predictors and effective strategies to manage immune reconstitution syndrome in patients with OIs, particularly TB, who have begun receiving ART.
There are hosts of unanswered questions regarding HIV therapy in the developing world that must be addressed by research. How will response to ART in resource-limited settings be affected by differences in human genetics, culture, diet, and comorbidities? Will the extraordinary successes of treatment and outstanding suppression of viral load by triple combination ART with an NNRTI be durable over 1, 2, 5, or even 10 years? In a setting in which access is highly challenging and patients may be starting and stopping treatment, will NNRTI resistance develop quickly, and will NNRTI-resistant virus be transmitted, leading to primary resistant HIV infection? What are the best and least expensive second-line regimens? Will patients, once they achieve dramatic improvement of their health, continue to be committed to treatment? Other, larger issues regarding broad-scale implementation of ART must be addressed, including the tremendous needs in health-care infrastructure, education and training of health care professionals in the areas of HIV and AIDS, low-cost monitoring of therapy, the introduction of new technologies, and secondary prevention to reduce new infections. The study by Cassol et al., along with many others that have appeared within the past 12 months, clearly demonstrates that triple combination ART is extraordinarily effective and practical in resource-limited settings, even in patients with low CD4+ cell counts and active OIs. Broad-scale implementation of this life-saving treatment must be widely supported not just by medical communities but also by governments, industry, and philanthropic groups worldwide. As treatment is implemented, an aggressive research agenda must be pursued in parallel, to determine how best to deliver ART, sustain it, and prevent new HIV infections worldwide, as well as improve the lives of those already infected.