Linda Ahdieh

The appropriate immunologic stage of human immunodeficiency virus infection at which to initiate highly active antiretroviral therapy (HAART) among asymptomatic persons is a core question. A cohort approach using longitudinal data from the US Multicenter AIDS Cohort Study was used to mimic a clinical trial to assess the risk of acquired immunodeficiency syndrome (AIDS) by timing of therapy. Three treatment groups were defined according to CD4⁺ count (cells/µl) at HAART initiation between July 1995 and January 2000: n = 127), 200–349 (deferral to 200–349, n = 130), and 350–499 (immediate treatment, n = 92). Survival analysis was used to compare time to AIDS between groups from the index visit until July 2000. The index visit for the immediate group was the one prior to HAART initiation. For the deferral groups, the index visit was a randomly selected, pre-HAART, AIDS-free visit after July 1990 at which CD4⁺ counts were 350–499 cells/µl. This strategy accounted for lead time bias. Compared with immediate treatment, the relative hazards of AIDS were 2.68 (p = 0.003) and 1.05 (p = 0.897) for deferral to <200 cells/µl and 200–349 cells/µl, respectively. These results support recent US public health guidelines for deferring HAART initiation until a count of <350 cells/µl. Furthermore, results suggest a potential threshold for HAART initiation in the neighborhood of 275 cells/µl.

Human immunodeficiency virus (HIV) infection and related immunosuppression are associated with excess risk for cervical neoplasia and human papilloma

During the past decade, there has been a dramatic increase in the number of women infected with HIV and the number of women with clinical AIDS. One of the most prominent features of HIV infection is that it is usually diagnosed during the peak reproductive years, and in 1998, HIV/AIDS was the fourth leading cause of death among women between the ages of 25 and 44 years. For this reason, there has been long-standing concern regarding the obstetric implications of HIV infection: both the impact of pregnancy on possibly accelerating the course of HIV disease and the impact of HIV infection on the course of pregnancy. There appears to be some immunologic changes associated with pregnancy, but they are not dramatic, and immune markers generally resume their prepregnancy values after delivery. With regard to long-term effects of pregnancy on HIV disease progression, no study to date has shown significant increases in mortality or in AIDS incidence associated with pregnancy. Studies have generally been small, however, and none have accounted for antiretroviral therapy usage. Many studies have shown that certain adverse outcomes are more common in HIV-positive pregnant women as compared with HIV-negative pregnant women, and concerns have been raised that spontaneous abortions may be more common among HIV-infected women and that this may impact fertility rates. Although important understanding has been acquired regarding the associations between pregnancy and the course of HIV infection, much remains to be understood. Additional, well-designed studies are clearly needed to rigorously address the many remaining questions that exist. We can anticipate that the resolution of these questions will continue to be of broad public health interest as the epidemic impacts increasing numbers of women, a large fraction of whom will be adolescents.

To characterize selection factors related to therapy initiation, the authors investigated the extent to which key markers of human immunodeficiency virus (HIV) disease severity were associated with initiation of potent antiretroviral therapy (ART). Logistic regression was used to determine the effects of CD4⁺ cell count and HIV RNA level on potent ART initiation during 6-month periods among 2,059 HIV-infected US women enrolled in the Women's Interagency HIV Study. Low CD4⁺ counts and high HIV RNA levels were significantly (p < 0.05) associated with initiation of potent ART. During all periods between April 1996 and March 1998, CD4⁺ counts were more strongly associated with potent ART initiation than HIV RNA levels were; however, during the last period, both were associated (odds ratio per 100 CD4⁺-count decrease = 1.17, p < 0.01; odds ratio per 1 log₁₀ increase in HIV RNA level = 1.48, p < 0.05). For a CD4⁺ count of 500 cells/ml and an HIV RNA level of 5,000 copies/ml, the probability of potent ART initiation increased from 0.5% to16.8% between October 1995–March 1996 and October 1997–March 1998, suggesting earlier initiation of potent ART. Given the documented occurrence of confounding by indication, prospectively collected, time-dependent data on markers of disease progression and therapy use should be considered when making population-level comparisons before and after introduction of potent ART. Am J Epidemiol 2000;152:923–33.

Increased risk for cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HlV)-infected women may be explained by repeated positivity of human papillomavirus (HPV) infection facilitated by HIV infection and related immunosuppression. As part of a longitudinal study with semiannual examinations, 268 women in Baltimore, Maryland (of whom 184 were HIV+), provided 1, 426 cervicovaginal lavage specimens tested for HPV DNA by a polymerase chain reaction-based assay between 1992 and 1998. HPV positivity and time to HPV clearance according to HIV serostatus and CD4⁺ cell count were compared using models for correlated binary data and survival analysis. Of the 187 participants who had at least one positive measurement, the probability of subsequent HPV positivity among HIV+ women and HIV⁺ women with CD4⁺ ≧200 and p< 0.001). Within-women HPV results were correlated (i.e., clustered) in each group (p< 0.01). Compared with HIV- participants, the relative incidence of HPV clearance was 0.29 and 0.10 among HIV+ women with CD4+≧200 and p < 0.001). At the end of follow-up, 11 women had biopsy-confirmed CIN. The association of HIV and CIN (p = 0.014) was fully explained by repeated HPV positivity induced by HIV infection (p = 0.648). Reversal of immunosuppression following potent antiretroviral therapy must be expected to have a dramatic impact on HIV-related CIN. Am J Epidemiol 2000; 151: 1148-57.