Around the year 2000, Anne E. Goldfeld, Harvard Medical School and GHC, started to see wasting and dying caused by AIDS in Cambodia, which previously had been largely spared from that epidemic. Many children were taking care of their dying parents, and others were themselves infected. “We were overwhelmed about how to handle this,” said Goldfeld. From private sources, she and her colleagues were able to obtain the funds needed to keep 100 people alive for 1 year. They also began conducting research through the Comprehensive International Program for Research on AIDS (CIPRA), partly because they knew this work would help get AIDS drugs into the country. And they convinced the photographer James Nachtwey to come to Cambodia to document the country’s joint epidemic of AIDS and TB, helping to shed light internationally on this problem, which was under-appreciated at the time. Goldfeld noted that between a quarter and a half of the 30 million people with HIV infection who have died have actually died of TB, which is curable even in a setting with a high prevalence of AIDS.
Goldfeld and her colleagues have been performing hypothesis-driven research in Cambodia to understand the molecular basis of TB’s natural history and to develop operational models for treating the disease, particularly in patients coinfected with HIV. TB and HIV infection each result in a host immune response, which in turn boosts the natural progression of the other pathogen. TB infection usually occurs first, followed by HIV infection, progression to AIDS, and extraordinarily high mortality, particularly when the CD4 level dips below 200. (Goldfeld pointed out that reinfection with TB also is very common in immunosuppressed HIV positive individuals.) When Goldfeld’s team began their research, the international recommendation from WHO was to start antiretroviral therapy for HIV at 2 months following diagnosis. Some data from retrospective studies indicated that an earlier start to therapy produced better outcomes, but drug–drug interactions were a concern for coinfected patients—for example, rifampicin speeds up the cytochrome P450 system of the liver, which increases side effects and the burden of taking medicines.
Goldfeld and her colleagues proceeded to explore the hypothesis that early initiation of antiretroviral therapy would increase survival in coinfected patients despite a more complex initial clinical management. With the support of the Agence Nationale de Recherche sur le SIDA, the NIH Division of AIDS, and the Institut Pasteur in Cambodia, the research team, together with the Cambodian Health Committee, developed five clinical sites in
1 This section is based on the presentation by Anne E. Goldfeld, Professor of Medicine, Harvard Medical School; and Co-Founder, GHC.