Leprosy and HIV infection (rarely the twain shall meet?).

colleagues report data from a long term seroprevalence study to evaluate the association of HIV infection and leprosy among patients seen at their clinic in Agra, India (). In the period from 1989 to 1993, 5 of 4025 leprosy patients (0.12%) were HIV positive, whereas in the period from 1999 to 2004, 5 of 2125 (0.38%) were HIV positive. This increase is not significant despite the apparent major increase in HIV infections among subjects screened at the same clinic. In 2004, among 387 persons who were “voluntarily” screened at their request, the HIV prevalence was 40.3%, and it was 43.4% among 106 persons referred for screening (). From this it appears that the prevalence of HIV infection has not increased in patients with leprosy despite evidence of a substantial HIV epidemic among the population served by the clinic. So why hasn’t the HIV prevalence increased in a comparable fashion among leprosy patients? Are they resistant or immune to HIV infection? In the past few years some individuals have been identified who are immune to HIV infection despite repeated exposure to the virus. One such group are persons who are homozygous for a 32 base pair deletion in the CCR5 gene that renders them completely resistant to infection with HIV-1 viruses that require attachment to the CCR5 co-receptor to enter the target CD4+ lymphocyte and replicate ( ). Individuals who are heterozygous for the CCR5 deletion are partially resistant to HIV-1 infection and progress more slowly after infection (). Also persons with genetic mutations in the CCR2 and SDF-1 genes progress more slowly after acquiring an HIV-1 infection (). These critically important discoveries have had major ramifications in our understanding of the biology of HIV-1 infections in humans. Another group of individuals who are partially resistant to HIV-1 infection are those who are heterozygous for HLA alleles (). Also, subjects who are heterozygous for HLA-B or DR alleles when compared to their HIV-1 positive sex partner appear to be less readily infected than persons who are homozygous with their partner for these genetic loci. However, this resistance to transmission is only relative, not absolute like homozygozity for the 32 base pair deletion in the CCR5 receptor ( ). In addition, some patients appear to acquire relative resistance to HIV infection or progression of HIV. Persons who are coinfected with GB virus C, a retrovirus that also infects macrophages and lymphocytes, appear to have slower progression of HIV, and lower HIV viral loads during their GB virus viremia, which is often chronic ( 19, ). Whether or not they are resistant to HIV-1 transmission, as well, has not been determined. Other infections, which have been reported to slow or delay the progression of HIV, and decrease the HIV-1 viral load in infected individuals, include scrub typhus (O. tsutsugamushi), Dengue, and measles ( 17, ). The proposed mechanism for the negative interaction between these infections and HIV-1 also involve the CCR5 coreceptor, which is also the receptor for the Beta chemokines, MIP-1 alpha, MIP-1 beta, SDF-1 and RANTES. These chemokines regulate the immune response and attach to receptors on CD4+ lymphocytes blocking the ability of HIV-1 to attach to and enter CD4+ lymphocytes to produce more viral copies. Could M. leprae infection also interfere with HIV-1 attachment and entry into CD4+ lymphocytes by attaching to the chemokine receptor? This seems very doubtful for a number of reasons. Whereas untreated patients with polar or borderline lepromatous COMMENTARY