Triple-Drug Therapy Promising Against African HIV Subtype

Triple-drug antiretroviral regimens that are widely used in the United States and Europe against one HIV-1 subtype appear to be effective in South African patients infected with a different HIV-1 subtype who also have tuberculosis (TB) or Kaposi’s sarcoma (KS), according to a study published in the Feb.1 issue of The Journal of Infectious Diseases, now available online. The South African subtype, known as subtype C, is rapidly spreading in developing countries, where TB and KS are major factors in AIDS morbidity and mortality. Since the triple-drug regimens have markedly reduced the morbidity and mortality associated with the subtype that predominates in developed countries (subtype B), the implication is that they may be similarly effective against the C subtype in developing countries as well.

The authors, Edana Cassol and coworkers in Durban, South Africa and the United States, studied 49 patients with previously untreated HIV-1 infection, 21 of whom had pulmonary TB and 28 of whom had KS. Patients in the TB group first received standard TB treatment, then an antiretroviral combination that has been successfully used to treat HIV-1 subtype B infections in patients with active TB–didanosine, lamivudine, and efavirenz, all purchased from Western manufacturers. KS patients received a combination of generic stavudine, lamivudine, and nevirapine, all manufactured in India; some also received cancer chemotherapy. Responses to antiretroviral therapy were measured in part by plasma HIV RNA levels and the number of peripheral blood CD4 cells, which help to orchestrate immune responses.

After three months, 94 percent of the TB group and 80 percent of the Kaposi group had undetectable HIV RNA levels–rates equivalent to or better than those in studies involving Western patients infected with the B subtype. The decrease occurred rapidly during the first 7 days of treatment, then gradually until virus was undetectable–a pattern reported in Western B subtype-infected patients. Similarly, both TB patients and KS patients experienced an early rise in CD4 cell numbers, then a small decrease, followed by a second increase–a pattern also noted in patients treated for subtype B infection.

The investigators concluded that their findings suggest that treatment of C-subtype HIV-1 infections with regimens that have been used against B-subtype infections “will have significant virological and immunological benefit, even in the setting of opportunistic infection and low CD4 counts.”

In an accompanying editorial, Timothy P. Flanigan and coworkers in Providence, Rhode Island, Denver, Colorado, and Chennai, India, commented that the findings of this study, along with those of other recent studies, have shattered two myths about treating HIV infection in the developing world: that the benefits obtained in developed countries cannot be replicated in poor settings, and that patients in developing countries are too ill with opportunistic diseases to benefit from antiretroviral therapy. They pointed out, however, that the long-term effects of treatment will need to be demonstrated in further studies by Cassol and coworkers and other investigators.