shows subject characteristics at the visit just prior to HAART initiation, stratified by HAART adherence. No associations were observed between adherence and age, race, CD4+ count, number of sex partners in the prior 6 months, or smoking. There were also no cross-sectional differences in the prevalence of HPV or cytologic abnormalities at the visit prior to HAART initiation.
Selected characteristics of Adherent and Non-adherent HAART users at the visit just prior to HAART initiation.
We then compared oncogenic HPV prevalence rates before and after HAART initiation. The average prevalence of oncogenic HPV decreased 36% in adherent women (from 22% before to 14% after HAART initiation), and 12% in non-adherent individuals (from 24% to 21%, respectively). The changes related to HAART were more clearly and accurately reflected in our multivariate mixed effects models, adjusted for covariates (see Methods). Specifically, adherent women had a highly significant reduction in oncogenic HPV prevalence following their initiation of HAART (odds ratio [OR]after vs before, 0.60 [95% confidence interval [CI], 0.44–0.81]; p=0.001), whereas non-adherent HAART use was not significantly associated with a change in oncogenic HPV prevalence (). A direct comparison of rates in adherent versus non-adherent women after HAART initiation suggested an approximately 30% reduction in oncogenic HPV prevalence related to adherence (ORadherent vs non-adherent, 0.70 [95% CI, 0.48–1.01]; p=0.06).
Adherent HAART use and the prevalence, incident detection, and clearance of HPV and squamous intraepithelial lesions (SIL).
Adherent HAART use was also associated with a reduction in the incident detection rate of oncogenic HPV. Specifically, the rate of incident detection decreased 33% from a mean of 5.4 per 100 person-visits to 3.4 per 100 person-visits in adherent women, whereas in non-adherent women it decreased 9% from 6.1 per 100 person-visits to 5.6 per 100 person-visits. In multivariate frailty models, adherent HAART use (hazard ratio [HR]after vs before, 0.49 [95% CI, 0.30–0.82]; p=0.006) but not non-adherent HAART use was associated with reduced incident oncogenic HPV detection, and the difference in incident detection rates between the two groups was significant (ORadherent vs non-adherent, 0.49 [95% CI, 0.28–0.86]; p = 0.01).
For analysis of HPV clearance the data proved too limited to study oncogenic HPV alone. Therefore, we studied clearance of any HPV (oncogenic and/or non-oncogenic HPV types) and found that adherent users had marginally greater clearance of any HPV after compared with before HAART (HRafter-vs-before 1.28 [0.99–1.66];p=0.06), whereas there was no relation with non-adherent HAART use (HRafter-vs-before 1.05 [0.86–1.29];p=0.63).
shows the relationship between adherent HAART use and SIL. Our major endpoint was oncogenic HPV-positive SIL (oncHPV+ SIL), lesions that are thought to have potential to result in tumors. Adherent users had a significant reduction in oncHPV+ SIL prevalence after HAART initiation (ORafter-vs-before 0.40 [0.18–0.88];p=0.02), that was non-significantly greater than the reduction in non-adherent patients (ORadherent-vs-non-adherent 0.68 [0.25–1.80];p=0.40). Although incident detection of oncHPV+ SIL was not significantly associated with HAART use, there was a significant relation of adherent HAART use with the rate of oncHPV+ SIL clearance (HRafter-vs-before 2.35 [1.07–5.18];p=0.03), that was significantly greater than the oncHPV+ SIL clearance rate observed among non-adherent women (HRadherent-vs-non-adherent 3.75 [1.43–9.88];p=0.007).
shows the characteristics of the subcohort at the visit just prior to HAART initiation, stratified by HAART effectiveness (i.e., whether or not HIV RNA levels were reduced >90% or to undetectable levels). The sample size is slightly smaller (n=254) than for the analysis of HAART adherence due to missing data. No significant differences were observed in this cross-sectional comparison. However, those with effective HAART (65%) were on average more likely than those with ineffective HAART (35%; P<0.001) to report having been adherent during follow-up (and vice versa, in 65% of those who were adherent users HAART was effective).
Selected characteristics and outcomes of Effective and Not-effective HAART users at the visit right before HAART initiation.
The average prevalence of oncogenic HPV decreased 20% in patients using effective HAART (from 20% before to 14% after HAART initiation), and did not decrease but actually increased slightly from 22% to 24%, respectively, in those using ineffective HAART. In multivariate models effective HAART was marginally associated with reduced oncogenic HPV prevalence (ORafter vs before, 0.71 [95% CI, 0.50–1.02]; p=0.06), and significantly associated with the prevalence of any HPV (ORafter vs before, 0.72 [95% CI, 0.60–0.88]; p=0.002) (). The incident detection of oncogenic (HRafter vs before, 0.62 [95% CI, 0.38–1.02]; p=0.06) and any HPV (HRafter vs before, 0.64 [95% CI, 0.46–0.92]; p=0.005) were also very similar in their associations with effective HAART use.
Effective HAART use and the prevalence, incident detection, and clearance of HPV and squamous intraepithelial lesions (SIL).
Ineffective HAART, in contrast, while having a marginal association with oncogenic HPV prevalence in multivariate models (ORafter vs before, 0.79 [95% CI 0.50–1.02]; p=0.06), had no associations with incident detection of oncogenic HPV or with prevalent/incident detection of any HPV. Clearance of any HPV was not associated with either effective or ineffective HAART.
shows the relationship between HAART effectiveness and SIL. The findings were fairly similar for both oncHPV+ SIL and any SIL, but only the results for any SIL, with its greater number of endpoints, reached statistical significance. Specifically, effective HAART was non-significantly associated with reduced prevalence of oncHPV+ SIL (ORafter-vs-before 0.47 [0.19–1.16];p=0.10), and significantly associated with any SIL (ORafter-vs-before 0.45 [0.25–0.80];p=0.007), whereas ineffective HAART use was not associated with prevalence of any SIL or oncHPV+ SIL. The data were more limited for the analysis of incident SIL (see Methods), and while the observed HRs were in the expected (inverse) direction, only the relationship between ineffective HAART and the incident detection of any SIL reached significance. SIL clearance, however, like SIL prevalence, had a significant association with effective (HRafter-vs-before 2.48 [1.10–5.61];p=0.03) but not ineffective HAART (HRafter-vs-before 1.26 [0.53–2.99];p=0.60).