Table 2. Multivariable analysis of factors associated with nonadherence to primary prophylaxis against Pneumocystis jirovecii pneumonia (PCP) – Supplement to HIV/AIDS Surveillance (SHAS) project, 2000–2004. Characteristics Illicit drug use in last year No Marijuana only Non-injection drugs other than marijuana Injection drug use Number of days mental health described as not good last month 0 $1 ,200 $200 Recent CD4 count (cells/mL) Unknown/missing On ART, always adherent On ART, usually adherent Antiretroviral therapy (ART) in the past month On ART, sometimes, rarely, or never adherent On ART, unknown or missing information about adherence Not taking ART Adjusted Odds Ratio (95% Confidence Interval)* N = 1,666 Reference 1.6 (1.1–2.4) 1.5 (1.0–2.1){ 2.3 (1.3–4.1) Reference 1.6 (1.2–2.2) 1.6 (1.1–2.2) Reference 0.9 (0.6–1.4) Reference 9.6 (6.7–13.7) 18.4 (11.1–30.4) 2.7 (1.5–4.7) 5.1 (3.3–8.1) *In addition to adjusting for variables included in this table, we controlled for region of residence in the U.S. and year of SHAS interview. {P-value,0.05. doi:10.1371/journal.pone.0005002.t002 (adjusted odds ratio [aOR]: 2.3; 95% confidence interval [CI]: 1.1–4.9) and having taken ART usually (aOR: 9.2; 95% CI: 5.5– 15.5) or sometimes/rarely/never (aOR: 26.8; 95% CI: 13.1–54.5) as prescribed, having taken ART but having unknown or missing information about adherence to ART (aOR: 2.6; 95% CI: 1.2– 5.3), or not having taken ART (aOR: 4.8; 95% CI: 2.6–9.1) in the past month were independently associated with nonadherence to primary PCP prophylaxis. The risk of nonadherence to PCP prophylaxis was almost three times as high among persons who reported having sometimes/rarely/never been adherent with ART as it was among those who reported having usually been adherent with ART during the preceding month. When we used the more restrictive definition of nonadherence to PCP prophylaxis during the past month (i.e., defining it as taking PCP medications sometimes, rarely, or never), our findings on multivariable analysis did not change appreciably (data not shown). However, description of mental health as not good for $1 day in the past month did not remain in the model and injection drug use during the past year was no longer an independent risk factor for nonadherence using the more restrictive definition of nonadherence. Of the 305 persons who reported that they did not take primary PCP prophylaxis exactly as prescribed during the month before interview, 264 (86.6%) reported the primary reason why they did PCP Prophylaxis Nonadherence not do so. Side effects were cited by 21.6%; difficulties with access to care or obtaining/taking medications were reported by 13.6%; and problems with scheduling, difficulty remembering to take the medication(s), or lack of perceived necessity were listed by 64.8% of subjects (Table 3). The most common reason cited for not taking PCP prophylaxis was forgetting to take it. Discussion In a large cohort of persons living with HIV infection, we found that almost one-fifth were nonadherent to primary PCP prophylaxis. We found that nonadherence to PCP prophylaxis was associated with illicit drug use, mental health issues including depression, nonadher- ence to prescribed ART, and low CD4 cell count. Our findings regarding illicit drug use are consistent with those of several studies evaluating adherence to ART [16,17,18,19,20,21,22,23], however current drug use was not found to be an independent risk factor in either study evaluating risk factors for nonadherence to PCP prophylaxis [11,12]. We did not find nonadherence to be associated with age, race/ethnicity, or daily pill burden, factors which have previously been reported to be associated with increased risk for nonadherence to PCP prophylaxis and/or ART. Consistent with our findings, Eldred and colleagues found that a high Mental Health Inventory-5 score, which indicates better mental health, was associated with adherence to PCP prophylaxis [12]. Lundberg and colleagues found that persons with current psychiatric illness were more likely to be nonadherent to PCP prophylaxis; however they did not find this condition to be an independent risk factor for nonadherence [11]. Additionally, mental health issues have been associated with nonadherence to ART in several studies [16,23,24,25,26]. It is possible, though, that persons with better mental health may report adherence to medications more accurately than persons with poorer mental health. Persons who reported being nonadherent to primary PCP prophylaxis were much more likely to report also being nonadherent to ART, which is consistent with the findings of Lundberg and associates [11]. We found that the risk of nonadherence to PCP prophylaxis was highest among those with the highest levels of reported nonadherence to ART medications. We found that low CD4 cell count was independently associated with nonadherence to PCP prophylaxis. However, 29% of respondents reported having recent CD4 cell counts that were $200 cells/mL, and 32% could not provide information about their most recent CD4 cell count. Respondents whose most recent CD4 cell counts were $200 cells/mL may have been started on PCP prophylaxis based on a declining trend in CD4 cell counts, may not have had CD4 cell counts that were $200 cells/mL for at least 3 months, or may not have accurately recalled their most recent CD4 count. When we limited our analysis to persons who reported that their most recent CD4 cell count was ,200 cells/mL, our findings did not change appreciably. Among subjects reporting they had a CD4 count ,200 cells/mL, recent injection drug use and nonadherence to ART remained independent predictors for nonadherence to PCP prophylaxis; however, non-injection drug use did not remain an independent risk factor. Although several studies have found that nonadherence to PCP prophylaxis and/or ART was associated with age [19,23,24,25] or race/ethnicity [11,23], we did not find nonadherence to PCP prophylaxis to be independently associated with these or other sociodemographic characteristics. In addition, we found that daily pill burden was not associated with nonadherence to PCP prophylaxis, which contradicts the findings of several studies that have found that an increased number of ART pills taken daily is PLoS ONE | www.plosone.org 5 March 2009 | Volume 4 | Issue 3 | e5002