Determinants of newly detected human papillomavirus infection in HIV-infected and HIV-uninfected injection drug using women.

BACKGROUND: We sought to identify factors associated with newly detected human papillomavirus (HPV) infection in a high-risk cohort of injection drug using women in Baltimore, MD. METHODS: We studied 146 HIV-infected and 73 HIV-uninfected female participants in a 5-year prospective HIV natural history study. We examined the association of sexual and nonsexual risk factors and newly detected type-specific HPV infection as determined by consensus PCR between consecutive visits. RESULTS: Newly detected HPV was more common among HIV-infected versus HIV-uninfected women (30% and 6%, respectively; P <0.01). Among the entire cohort, recent crack use (OR, 1.7; 95% CI, 1.1-2.6) and HIV infection/CD4 cell count were independent predictors for new HPV detection (HIV-uninfected as reference, OR, 4.6; 95% CI, 2.3-8.9, OR, 5.4; 95% CI, 2.8-10.3, and OR, 10.9; 95% CI, 5.5-21.7 for HIV-infected CD4 >500, 200-500, and <200, respectively). Among HIV-uninfected women, recent marijuana use was an independent predictor of newly detected HPV infection (OR, 3.5; 95% CI, 1.3-9.5). CONCLUSIONS: Newly detected HPV clearly increased with greater immunosuppression in HIV-infected injection drug users. Larger studies of HIV-uninfected and infected high-risk individuals are needed to clarify the independent associations of crack and marijuana use with new (or reactivated) HPV infection.

Prevalence of hepatitis C virus infection among injection drug users in the United States, 1994-2004.

OBJECTIVE: To examine hepatitis C virus (HCV) seroprevalence among injection drug users in 4 US cities from 1994 through 2004. METHODS: Demographic characteristics, behaviors, and prevalence of HCV antibody among 5088 injection drug users aged 18-40 years from Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and New York, New York, enrolled in 3 related studies--Collaborative Injection Drug User Study (CIDUS) I (1994-1996), CIDUS II (1997-1999), and CIDUS III/Drug User Intervention Trial (2002-2004)--were compared using the chi(2) and Mantel-Haenszel tests of significance. Trends over time were assessed by logistic regression. RESULTS: Prevalence of HCV infection was 65%, 35%, and 35% in CIDUS I, CIDUS II, and CIDUS III, respectively. The adjusted prevalence odds ratio (OR) of being HCV antibody positive increased with the number of years of injection drug use (OR, 1.93 [95% confidence interval {CI}, 1.68-2.21] for each year of injecting within the first 2 years; OR, 1.09 [95% CI, 1.07-1.11] for each year of injecting beyond the first 2 years). Significant decreases were observed in the prevalence of HCV antibody between CIDUS I and CIDUS III in Baltimore (OR, 0.30; 95% CI, 0.20-0.43) and Los Angeles (OR, 0.17; 95% CI, 0.09-0.31) and among people of races other than black in Chicago (OR, 0.12; 95% CI, 0.08-0.17). No decrease in prevalence was seen in New York (OR, 1.04; 95% CI, 0.69-1.58) or among blacks in Chicago (OR, 0.55; 95% CI, 0.16-1.90). CONCLUSION: Although regional differences exist, our data suggest that the incidence of HCV infection among injection drug users in the United States decreased from 1994 through 2004.

Clinical course of recurrent respiratory papillomatosis in Danish children.

OBJECTIVE: To evaluate the clinical course of juvenile-onset recurrent respiratory papillomatosis (RP) with respect to age, disease duration, and maternal condylomas. DESIGN: Inception cohort study. SETTING: All ear, nose, and throat departments in public Danish hospitals. PATIENTS: Fifty-seven Danish children diagnosed with RP and born between 1974 and 1993 were observed for an average of 14 years after diagnosis. MAIN OUTCOME MEASURE: Removal of respiratory papillomas by knife biopsy, laser surgery, or cryotherapy. RESULTS: Children younger than 5 years diagnosed with RP underwent an average of 4.1 surgeries in the first year of disease, the highest rate among all our patients. The overall surgery rate decreased over time after initial diagnosis but remained significantly higher for children with a younger age of onset for the first 4 years of disease (P <.001) and for children with a maternal history of condylomas in pregnancy for years 4 to 10 of the disease (P <.001). We also observed an independent and statistically significant (P <.001) decreasing surgery rate with increasing age and time from initial diagnosis. The trend for children with recurrent disease was a decreasing rate of surgical procedures (28 of 42 patients with recurrent disease); however, a third of patients (14/42) demonstrated a constant or increasing rate of surgical procedures over time. CONCLUSIONS: The clinical course of RP is characterized by a high frequency of surgeries soon after diagnosis that diminishes over time and with increasing age. Additional studies are warranted to identify factors associated with cases that do not conform to the usual disease course.

Factors and temporal trends associated with highly active antiretroviral therapy discontinuation in the Women's Interagency HIV Study.

We characterized factors and temporal trends associated with discontinuation of highly active antiretroviral therapy (HAART) among 936 HIV-infected women enrolled in the Women's Interagency HIV Study. A multivariate analysis of post-HAART initiation exposures found that high HIV RNA levels (relative hazard [RH] = 1.36, P < 0.001) and high depressive symptom scores (RH = 1.53, P = 0.012) were associated with HAART discontinuation. The adjusted hazard of discontinuation was higher in the 2 most recent calendar periods compared with the first (RH = 1.61, P = 0.026; RH = 1.56, P = 0.074, respectively). The increasing risk of HAART discontinuation in recent calendar periods and changes in the clinical factors associated with discontinuation reflect ongoing and dynamic shifts in the approach to HAART utilization.

Effects of bacterial vaginosis and other genital infections on the natural history of human papillomavirus infection in HIV-1-infected and high-risk HIV-1-uninfected women.

BACKGROUND: Whether the natural history of human papillomavirus (HPV) infection is affected by bacterial vaginosis (BV) or Trichomonas vaginalis (TV) infection has not been adequately investigated in prospective studies. METHODS: Human immunodeficiency virus 1 (HIV-1)-infected (n=1763) and high-risk HIV-1-uninfected (n=493) women were assessed semiannually for BV (by Nugent's criteria), TV infection (by wet mount), type-specific HPV (by polymerase chain reaction with MY09/MY11/HMB01 HPV primers), and squamous intraepithelial lesions (SIL) (by cytological examination). Sexual history was obtained from patient report at each visit. Risk factors for prevalent and incident HPV infection and SIL were evaluated by use of multivariate models. RESULTS: BV was associated with both prevalent and incident HPV infection but not with duration of HPV infection or incidence of SIL. TV infection was associated with incident HPV infection and with decreased duration and lower prevalence of HPV infection. TV infection had no association with development of SIL. Effects of BV and TV infection were similar in HIV-1-infected and high-risk HIV-1-uninfected women. HIV-1 infection and low CD4(+) lymphocyte count were strongly associated with HPV infection and development of SIL. CONCLUSIONS: BV and TV infection may increase the risk of acquisition (or reactivation) of HPV infection, as is consistent with hypotheses that the local cervicovaginal milieu plays a role in susceptibility to HPV infection. The finding that BV did not affect persistence of HPV infection and that TV infection may shorten the duration of HPV infection helps explain the lack of effect that BV and TV infection have on development of SIL.

When to initiate highly active antiretroviral therapy: a cohort approach.

The appropriate immunologic stage of human immunodeficiency virus infection at which to initiate highly active antiretroviral therapy (HAART) among asymptomatic persons is a core question. A cohort approach using longitudinal data from the US Multicenter AIDS Cohort Study was used to mimic a clinical trial to assess the risk of acquired immunodeficiency syndrome (AIDS) by timing of therapy. Three treatment groups were defined according to CD4(+) count (cells/microl) at HAART initiation between July 1995 and January 2000: <200 (deferral to <200, n = 127), 200-349 (deferral to 200-349, n = 130), and 350-499 (immediate treatment, n = 92). Survival analysis was used to compare time to AIDS between groups from the index visit until July 2000. The index visit for the immediate group was the one prior to HAART initiation. For the deferral groups, the index visit was a randomly selected, pre-HAART, AIDS-free visit after July 1990 at which CD4(+) counts were 350-499 cells/microl. This strategy accounted for lead time bias. Compared with immediate treatment, the relative hazards of AIDS were 2.68 (p = 0.003) and 1.05 (p = 0.897) for deferral to <200 cells/microl and 200-349 cells/ micro l, respectively. These results support recent US public health guidelines for deferring HAART initiation until a count of <350 cells/microl. Furthermore, results suggest a potential threshold for HAART initiation in the neighborhood of 275 cells/microl.

Serum immunoglobulin A response to human papillomavirus type 16 virus-like particles in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.

Serum samples from 2008 human immunodeficiency virus (HIV)-positive and 551 HIV-negative women were tested for immunoglobulin A (IgA) to human papillomavirus (HPV) type 16 capsids. IgA seropositivity was lower than previously reported IgG seropositivity (7% vs. 51%), but, like IgG antibodies, HPV 16 IgA was associated with sexual behavior, cervicovaginal HPV 16 DNA, and cytological abnormalities. IgA seropositivity was higher in HIV-positive women than in HIV-negative women (7.7% vs. 4.9%; P=.02), but the association was lost after adjustment for HPV 16 cervicovaginal infection. IgA, but not IgG, seropositivity was associated with progression to high-grade cytological abnormalities (relative hazard [RH], 2.2 [95% confidence interval, 1.2-4.2]), raising the possibility that an IgA response to HPV 16, as described for other DNA viruses, may be a marker of persistent viral replication. The risk of incident infection with non-16-related HPV types was increased in IgA seropositive women (RH, 1.8 [95% confidence interval, 1.3-2.6]), compared with seronegative women (RH, 2.2 [95% confidence interval, 0.9-5.4]), but there was no difference in the risk of incident HPV 16 or HPV 16-related infections. This may be evidence of partial type-specific or clade-specific immunity conferred by seropositivity to HPV 16 capsids.

Highly active antiretroviral therapy and cervical squamous intraepithelial lesions in human immunodeficiency virus-positive women.

BACKGROUND: Women infected with human immunodeficiency virus (HIV) have an increased risk of persistent squamous intraepithelial lesions (SILs) of the cervix. We assessed the association between use of highly active antiretroviral therapy (HAART) and regression of SIL in HIV-infected women enrolled in the Women's Interagency HIV Study, a large, multicenter, prospective cohort study. METHODS: Of 2059 HIV-infected participants, 312 HIV-infected women had normal cervical cytology at baseline and were subsequently diagnosed during 7 years of follow-up with incident SIL. Pap smears, CD4+ T-cell counts, and information regarding use of HAART were obtained every 6 months. The outcome of interest was lesion regression, defined as two consecutive normal Pap smears 6 months apart. Incidence rates of SIL regression were computed among person-years at risk, both before and after HAART initiation. All statistical tests were two-sided. RESULTS: Of 312 women, 141 had lesions that regressed to normal cytology, with a median time to regression of 2.7 years. Overall, the incidence of regression increased (P(trend) =.002) over time after HAART was introduced. At incident SIL, median CD4+ T-cell counts were lower in women whose lesions did not regress than in women whose lesions regressed (230 versus 336 cells/microL; P<.01). Before HAART was introduced, the rate of lesion regression was 0.0% (95% confidence interval [CI' = 0.0% to 2.4%). After HAART was introduced, the rate was 12.5% (95% CI = 9.9% to 15.1%) and was related to post-HAART CD4+ T-cell counts (P(trend) =.002). CONCLUSIONS: HAART use was associated with increased regression of SIL among HIV-infected women, and among women who used HAART, increased CD4+ T-cell counts were associated with a greater likelihood of regression. However, the majority of cervical lesions among HIV-infected women, even among individuals who used HAART, did not regress to normal.

Serum immunoglobulin G response to human papillomavirus type 16 virus-like particles in human immunodeficiency virus (HIV)-positive and risk-matched HIV-negative women.

Baseline serum samples from 2815 human immunodeficiency virus (HIV)-positive and 963 HIV-negative women enrolled in 2 cohort studies were tested for immunoglobulin G antibodies to human papillomavirus type 16 (HPV-16) capsids. HPV-16 seropositivity was associated with lifetime number of sex partners (P<.001) among both HIV-positive and HIV-negative women. Approximately 50%-60% of HPV-16 DNA-positive women were HPV-16 positive. HPV-16 seropositivity was associated with HIV infection; however, after adjustment for baseline cervical HPV infection and disease, the association disappeared. Thus, the high seroprevalence of HPV-16 among HIV-positive women may be explained by a high prevalence of HPV of all types. Approximately 50% of HIV-positive women had serological evidence of prior HPV-16 infection, but only approximately 5% had an HPV-16 cervical infection at baseline. Despite the higher prevalence of HPV infection in this group, most HIV-positive women are able to control HPV-16 replication at the cervix, and reactivation, if it occurs, is not very common.