Women with cervicovaginal antibody dependent cell -mediated cytotoxicity have less genital HIV-1 RN

HIV infected women have high concentrations of HIV specific antibodies in their serum and cervicovaginal lavage (CVL). We assessed for the presence of antibodies that mediate antibody dependent cell-mediated cytotoxicity (ADCC) and evaluated the relationship of these antibodies to the disease status of the individual. ADCC titers of paired serum and CVL samples from 281 women who were participants in a sub-study of The Division of AIDS Treatment Research Initiative program, NIAID (DATRI 009), were determined using a standard 51Cr-release assay. Serial dilutions of patient samples were incubated with (i) 51Cr-labeled target cells that were coupled to HIV-1 gp120MN and (ii) PBMC from healthy donors. An individual was considered to have ADCC activity if activity at any dilution was more than 1 SD above the mean of comparable serum or CVL from HIV seronegative women. Major findings of this study include: (i) 93% of the women had ADCC activity in the serum or CVL. Of these women 43% (n = 122) had ADCC activity in the serum alone, 49% (n = 138) had ADCC activity in serum and CVL, 2% (n = 6) had ADCC activity in the CVL alone while 5% (n = 15) did not have antibodies that mediate ADCC activity against gp120; (ii) women with ADCC activity in the serum and CVL had a significantly lower mean genital viral load than women with activity in the serum alone (p = 0.05); (iii) women who were on anti-retroviral therapy and had serum ADCC activity have a lower mean concentration of plasma HIV-1 RNA than women without serum ADCC activity (p = 0.09); (iv) our study strongly suggests that IgG not IgA in the CVL may be responsible for mediating ADCC activity in the CVL (p < 0.001); and (v) the proportion of women with CVL ADCC activity and the concentration of HIV-specific antibodies in the CVL do not increase until women have >250 RBC/ml in the CVL. This study also investigates the relationship between ADCC activity in the serum and CVL with CD4+ T-cell numbers, ethnicity of women, and risk factors for acquiring HIV-1.