Selection by Indication of Potent Antiretroviral Therapy Use in a Large Cohort of Women Infected with Human Immunodeficiency Virus

Abstract

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% to 16.8% 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.

Impact of Protease Inhibitor-Containing Combination Antiretroviral Therapies on Height and Weight Growth in HIV-Infected Children

“…In these analyses, each child serves as his or her own control to reduce variability and control for the influence of some unmeasured factors (eg, genetic predisposition, possibly socioeconomic and nutritional status) on growth before and after PI use. However, as with any observational study, confounding by indication, 30 resulting from the fact that HIV-infected children who were selected to receive PI treatment earlier had on average lower CD4 cell counts and worse growth measures than children who did not receive a PI until later or not at all and thus might have worse prognosis and poorer responses to PIs, might still exist. Confounding by indication was stronger in the early years of the study (1996 and 1997), when children with the most advanced HIV disease were selected to receive PI treatments.…”

Human Leukocyte Antigen Genotype and Risk of HIV Disease Progression before and after Initiation of Antiretroviral Therapy

“…Inclusion of baseline CD4 ϩ count, HIV RNA level, and HCV infection in these models controlled for both initial disease status and the probability of selection by our stratified random sampling design; i.e., we essentially addressed the following question: among women who were otherwise similar in relation to starting immune status and HCV infection, did HLA genotype help explain the heterogeneity in HIV disease progression? These analyses were limited to the period prior to the widespread use of HAART to minimize the possibility of "confounding by indication" (i.e., selection bias related to early initiation of HAART [1]). Specifically, we censored all data after September 1996 when the prevalence of HAART use first exceeded 5% of WIHS subjects.…”

Protease Inhibitor Combination Therapy, Severity of Illness, and Quality of Life Among Children With Perinatally Acquired HIV-1 Infection

“…Studies showed that PI therapy was initiated sooner among children with lower CD4 ϩ cell counts and lower height and weight z scores, which introduces the need to control for confounding by severity of illness with indication for treatment. 11,13,17 Mean differences in QOL scores between treatment groups were initially estimated with univariate linear regressions. Multivariate regressions were then used to estimate differences between treatment groups while controlling for clinical factors associated with receipt of PI therapy and sociodemographic characteristics.…”

“…This selection according to indication also has been observed among adults with HIV infection and complicates evaluation of treatment. 17 Furthermore, regimens containing PIs are complex and raise concerns about both acute and long-term side effects. The regimens are often challenging to administer or take, because of the amount of medication required and problems with the availability and palatability of pediatric formulations of PIs.…”