In this cohort of HIV seropositive women, increased progression to AIDS and all-cause death was observed for distinct patterns and types of drugs used by non-parenteral routes of administration compared to those not reporting NIDU behaviors. By NIDU patterns, progression to AIDS was faster for both active (consistent and inconsistent) and former NIDU than never users, while all-cause mortality was significantly higher for former users and less so for consistent users than non-users. By type of NIDU, progression to AIDS was faster among stimulant and polydrug users than other groups, and all-cause mortality risks were lowest among depressant users. Progression to AIDS-related death did not differ by distinct patterns or types of NIDU behaviors.
Earlier laboratory studies of infection and immunity led to the hypothesis that worse clinical outcomes would be expected for inconsistent as opposed to consistent, former or non-use patterns of drug administration [11
]. While findings from the present study do not conform strictly to this hypothesis, other factors may have contributed to the observed results, namely, baseline immunological and virological status of participants and use of potent antiretroviral therapies. First, it appears that consistent users were less likely to report HAART utilization during the course of follow-up, despite similar baseline immunological and virological indicators between consistent, former and non-users. Similar findings of lower HAART initiation and utilization among women actively using drugs were noted in earlier reports [36
], and are in line with DHHS guidelines on initiation of antiretroviral therapies among active drug users when there are concerns of lower adherence to complex treatment regimens that may lead to greater resistance to these medications [31
]. Nonetheless, physicians should actively encourage HIV-positive women who report drug use to seek drug treatment and support services in order to address these potential barriers to medication uptake and adherence. Secondly, these results are plausible when noting that NIDU characterized by inconsistent pattern of use and exclusive use of depressants were more likely than the other categories of drug pattern or type to have both higher CD4+
levels and lower HIV viral loads at baseline as well as more widespread use of HAART throughout follow-up. While inconsistent use and use of depressants is still a concern, it appears that this group was considered by clinicians to be appropriate candidates for HAART. A potential explanation for the higher use of HAART among inconsistent users may be that clinicians will prescribe HAART to individuals who present as non-users during clinic visits, but who will report drug use at study interviews. Finally, we might have expected clinical progression in former users to be equivalent to non-users, but given that former users had lower CD4+
cell counts and higher HIV viral load levels at baseline, they can be characterized as sicker at baseline and more likely to experience a negative outcome during follow-up.
Upon closer inspection of AIDS-defining events reported during follow-up, almost 50% were characterized as pulmonary conditions, including Pneumocystis carinii
pneumonia (16%), candidias (15%), bacterial pneumonia (12%) and tuberculosis (6%). It must be noted that individuals reporting former and active NIDU (51%) were significantly more likely to report a pulmonary AIDS-defining illness compared with those who never engaged in NIDU (35%, P
-value = 0.034). The increased susceptibility to pulmonary illness among those who used drugs via non-parenteral modes of administration is attributed to the harmful effects caused by inhalation of smoke on proper respiratory functioning among HIV-positive individuals [38
]. The use of crack or cocaine has also been shown in previous studies to be associated with respiratory AIDS infections [39
] and may also explain the increased progression to AIDS among stimulant users observed here.
Previous studies have suggested that faster HIV progression in some groups may be related to unequal access to health care or utilization of health-care services, especially among individuals who use drugs [41
]. Specifically, injection drug use is associated with poorer utilization of out-patient medical services [42
]. It is unlikely that limited access or use of health-care services would account for our findings, as the majority of this sample was recruited from clinical settings across the United States; there was widespread reporting of health insurance coverage (either pubic or private) and overall health-care utilization, irrespective of NIDU pattern or type of NIDU. As recent reports have indicated differences in HAART initiation, especially if clinicians are concerned with adherence to complex therapeutic regimens and development of resistance due to non-compliance [37
]; these differences may have played a role in the findings observed here, given the lower proportion of active drug users reporting HAART compared with non-users.
Among individuals reporting HAART utilization, drug use has been cited as a major predictor of inadequate adherence to HAART [43
]. Howard and colleagues [44
] found that while a history of injection drug use was not associated with reduced adherence, active drug use predictive of lower adherence to antiretroviral medications. A recent cross-sectional analysis of factors associated with adherence to antiretroviral regimens in a subsample of the WIHS cohort showed that active use of cocaine, crack or heroin, irrespective of route of administration, was associated with lower adherence to HAART (OR = 2.27, 95% CI, 1.32–3.91) [45
]. Based on these previous findings, we examined whether adherence to HAART was associated with pattern or type of NIDU in the present report. However, a subsample analysis did not indicate significant differences in self-reported adherence to HAART by pattern or type of NIDU (data not shown). This suggests that the findings of increased risk for progression to AIDS and death by pattern and type of NIDU observed here were not related to differential treatment adherence by NIDU behaviors.
Several study limitations should be considered before conclusions are drawn. First, this study sample reflects recruitment of volunteers from HIV clinics, thus the extent to which these results are generalizable to other HIV infected women is difficult to determine. Secondly, although AIDS events were based on self-report, efforts were made to verify AIDS diagnoses via medical record abstraction and registry check. The results of these efforts suggest a high degree of accuracy of self-reported AIDS conditions compared to those reported to registries [46
]. Thirdly, ascertainment of cause of death from death certificates is a concern. Despite active and passive surveillance procedures, missing death reports may artificially lower mortality estimates, which can be a problem if this occurred differentially between groups. However, as many of these participants were recruited from clinical care settings, this concern is reduced. Fourthly, data on HAART utilization is also based on participant self-reports and may be subject to over-reporting. Finally, the validity and accuracy of self-reported drug use behaviors are often cause for concern as drug users may under-report drug use due to socially desirable responding [47
]. Results from toxicology analysis for cocaine and opiates on a subset of WIHS participants (n
= 168) suggest a high degree of validity in self-reported drug use behaviors [48
In conclusion, these findings suggest that distinct patterns and types of NIDU were associated with occurrence of AIDS and all-cause mortality but not AIDS-related death, as reported in this cohort of HIV seropositive women. While initiation of HAART was lower among active NIDU, these findings do not indicate reductions in the overall benefit of HAART among those women who did report the use of HAART, irrespective of drug use status. Although our findings on AIDS-related mortality are consistent with prior studies, differences in progression to AIDS events suggest that these results may have significant implications for future epidemiological research into drug use as a co-factor in HIV progression. The complex nature of and factors influencing drug use necessitates careful ascertainment of drug use behaviors and more precise examination in future analyses. Greater collaboration between researchers conducting laboratory and animal model trials and those conducting observational studies are also called for in order to understand better the dynamic interplay between long-term use of licit and illicit drugs and drugs of treatment, in particular HAART. In the meantime, health-care practitioners and public health educators need to develop appropriate interventions to address non-injection drug use among HIV seropositive individuals.