Background: Neutropenia is well described in individuals infected with human immunodeficiency virus (HIV) and occurs in approximately 10% to 50% of cases. Neither the effect of highly active antiretroviral therapy (HAART) on neutrophil counts nor the significance of neutropenia in terms of survival has previously been evaluated.Methods: The prevalence of neutropenia among 1729 HIV-infected women, followed up as part of the Women's Interagency HIV Study, was evaluated. The CD4 lymphocyte counts, HIV-1 RNA levels, and complete blood cell counts, including absolute neutrophil counts, were obtained at 6-month intervals.Results: Neutropenia was common among HIVinfected women; at baseline, 44% had neutrophil counts less than 2000/µL, whereas 7% had counts less than 1000/ µL. During 7.5 years of follow-up, neutrophil counts less than 2000/µL occurred on at least 1 occasion in 79%, whereas absolute neutrophil counts less than 1000/µL were documented in 31%. Worsening HIV disease parameters, such as lower CD4 cell counts (PϽ.001) and higher HIV-1 RNA levels (PϽ.001), were associated with development of neutropenia. Resolution of neutropenia was associated with higher CD4 cell counts (PϽ.001) and use of HAART (P=.007). We found that HAART, without zidovudine, was associated with protection against development of neutropenia. On multivariate analysis, neutropenia was not found to be associated with decreased survival among HIV-infected women.Conclusions: Worsening HIV disease parameters are associated with neutropenia in HIV-infected women. Treatment with HAART, without zidovudine in the regimen, protects against development of neutropenia, whereas HAART use and higher CD4 cell counts are associated with resolution of neutropenia. Neutropenia is not associated with decreased survival in HIV-infected women.