The interplay of factors surrounding the timing of HAART initiation is complex, and involves not only biologic factors such as immune function and disease progression, but also psychosocial and systems-based factors. A better understanding of these factors may help eliminate treatment barriers and enable healthcare providers to offer optimal care to all patients with HIV. This study’s findings show that in an environment providing no-fee open access care, certain factors previously demonstrated to affect the timing of HAART, namely race/ethnicity, age, gender and depression did not have the same impact in most patients in this cohort. This remained true with respect to timely initiation of primary PCP prophylaxis when indicated. However in the subset of patients in Group C who electively started HAART at higher CD4 cell counts without an indication, African American race/ethnicity was associated with lower odds of initiation.
The Department of Defense provides a healthcare system ensuring access to visits and medications for its beneficiaries. In addition, keeping appointments is reinforced for active duty members by their chain of command. This practice and the military’s culture of health provide a potential explanation for the absence of a statistically significant difference in the timing of HAART initiation when indicated across demographic groups in this cohort. However the potential impact of command-directed follow-up among active duty personnel may be suggested by the observation of a non-significant trend towards lower odds of HAART initiation among retired participants. Previous studies have underscored the importance of regular clinic follow-up on appropriate HAART use. In one study which showed a longer time to HAART initiation among black patients, the most common reasons for delays in referral to case conferences (where decisions were made about HAART) were lack of regular follow-up, active substance use, and the patient’s desire to not use HAART . There are fewer issues with access and follow-up in the U.S. military healthcare system. Also, the DoD Drug Demand Reduction Program with random urine drug screening has been very successful in decreasing substance abuse among active duty, especially with regard to intravenous drug use . Cultural differences in medication uptake and adherence have yet to be fully explored in the military setting, but preliminary evaluation suggests HAART adherence levels are equally high among a subset of African Americans and Caucasians .
African Americans in this study were less likely than Caucasians to electively start HAART at higher CD4 counts. And while there were no statistically significant ethnic differences among those with an indication for HAART, there remained a trend towards lower odds of HAART initiation at lower CD4 count thresholds among African American participants when compared with Caucasian participants. A number of previous studies observed disparities in HAART use among certain race/ethnic groups and women although these did not specifically evaluate the elective initiation of HAART at high CD4 counts [8–10, 14, 21, 23–26]. While the etiology of these disparities is largely attributed to differences in healthcare access, other factors have also been shown to contribute and perhaps offer an explanation for the findings in this study. For example, racial discordance of the physician-patient relationship may be associated with cultural miscommunication that could explain delays in receipt of HAART [12, 27]. Additionally, patients who reported that their provider “knows me as a person” were more likely to receive HAART than those who did not report this belief . Other factors may also impact decisions about HAART including health literacy and attitudes toward health [28, 29]. It is important to note that not all studies have shown racial/ethnic differences in the receipt of HAART. In a study performed among HIV-positive patients in Denmark, where healthcare is free, both white and nonwhite patients had similar rates of receiving HAART, and race/ethnicity did not have an apparent effect on the outcomes associated with HAART .
The implication of the ethnic difference in elective HAART initiation in this study is important because some studies have demonstrated a differential response to HAART between Caucasian and non-Caucasian groups [16, 17, 21, 31, 32]. In an analysis of antiretroviral-naïve patients with HIV who started HAART between 1997 and 2003, African American race/ethnicity was associated with failure to reach virologic suppression at 12 months  and at 6 months and 12 months after initiating HAART . And despite continuous use of HAART, black women experienced increased rates of AIDS-defining illness and death from AIDS when compared with white women . Interestingly, two studies suggest that in spite of decreased rates of virologic suppression, African Americans and Caucasians treated with HAART in the DoD have equivalent long-term outcomes [15, 18]. Pharmacogenomic and adherence differences are being explored as possible explanations for the lower virologic suppression rates.
Depression was not associated with the timing of HAART in this study among those with an indication to start, although it has been shown to impact the decision to start HAART in some previous studies [33, 34] but not all . There was a delay in HAART initiation in Group A due to the presence of severe symptoms, which may reflect the high median CD4 cell count among delayers in this group, a prioritization of disease management, or possibly a concern about immune reconstitution inflammatory syndrome (IRIS) among those with lower nadir CD4 cell counts. Prior mono- and dual-NRTI use was associated with decreased odds of starting HAART in Group B, but increased odds in Group C. This effect was highly associated with calendar year and may reflect delays in changing to HAART in the early HAART era in participants stable on non-HAART ART in Group B versus a preference for newer therapies in those electing to start HAART in Group C. A similar phenomenon in the early HAART era is suggested in a study examining the reasons why 28 of 60 patients treated for HIV in a U.S. health clinic were not treated with HAART in 1997-1998 in accordance with DHHS guidelines at the time . Another study also suggested delays in transitioning to the use of protease inhibitors in a U.S. practice in 1996 among 190 patients; higher CD4 cell count (200-500 cells/mm3) was a prominent factor in multivariate models .
There are some study limitations. It is a retrospective analysis covering a broad timeframe and involves five DoD research sites among which practice patterns may vary. Statistical models were adjusted to account for site of visit and service affiliation. While the cohort has a balance of male African American and Caucasian participants, other ethnic groups and women are represented in much smaller proportions, making it difficult to draw conclusions about the timing of HAART among these groups. Overall, the cohort is relatively small, and while we observed many trends that did not reach statistical significance, it is possible that these trends would represent clinically important differences in a larger cohort. Further, it is likely that there are additional confounding factors that we were not able to fully account for in the analysis. The criteria for determining eligibility for HAART initiation in this study are limited to the DHHS guidelines, even though other societies in the U.S. and worldwide have published guidelines that may have influenced practice patterns. And importantly, there are limited data on substance use in this cohort, although it is estimated to be quite low, with no IVDU reported at last survey .