Background

HIV-seropositive women face high risk for infection with oncogenic human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer, but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16 is highly oncogenic but only weakly associated with HIV status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types, which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer.

Objective

We sought to assess whether the underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers.

Study design

HIV-seropositive and HIV-seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia (CIN) grade ≥3 (CIN3(+)). DNA from >40 HPV types was detected by polymerase chain reaction in cervicovaginal lavage specimens obtained at the visit at which CIN3(+) was diagnosed.

Results

HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3(+) but only 44 (29%) of 154 HIV-seropositive women with CIN3(+) (P = .01). The lower prevalence of HPV16 in CIN3(+) among HIV-seropositive women persisted after controlling for covariates (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.08-0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3(+) (OR, 1.02; 95% CI, 0.53-1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV-seropositive vs HIV-seronegative women with CIN3(+) (OR, 3.9; 95% CI, 1.3-11.8).

Conclusion

The previously demonstrated increase in CIN3(+) incidence among HIV-seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV-seropositive women.

Cigarette smoking is an important risk factor for adverse health events in HIV-infected populations. While recent US population-wide surveys report annual sustained smoking cessation rates of 3.4–8.5%, prospective data are lacking on cessation rates for HIV-infected smokers. To determine the sustained tobacco cessation rate and predictors of cessation among women with or at risk for HIV infection. Prospective cohort study. A total of 747 women (537 HIV-infected and 210 HIV-uninfected) who reported smoking at enrollment (1994–1995) in the Women’s Interagency HIV Study (WIHS) and remained in follow-up after 10 years. The participants were mostly minority (61% non-Hispanic Blacks and 22% Hispanics) and low income (68% with reported annual incomes of less than or equal to $12,000). The primary outcome was defined as greater than 12 months continuous cessation at year 10. Multivariate logistic regression was used to identify independent baseline predictors of subsequent tobacco cessation. A total of 121 (16%) women reported tobacco cessation at year 10 (annual sustained cessation rate of 1.8%, 95% CI 1.6–2.1%). Annual sustained cessation rates were 1.8% among both HIV-positive and HIV-negative women (p = 0.82). In multivariate analysis, the odds of tobacco cessation were significantly higher in women with more years of education (p trend = 0.02) and of Hispanic origin (OR = 1.87, 95% CI = 1.4–2.9) compared to Black women. Cessation was significantly lower in current or former illicit drug users (OR = 0.42 95% CI = 0.24–0.74 and OR = 0.65, 95% CI = 0.49–0.86, respectively, p trend = 0.03) and women reporting a higher number of cigarettes per day at baseline (p trend < 0.001). HIV-infected and at-risk women in this cohort have lower smoking cessation rates than the general population. Given the high prevalence of smoking, the high risk of adverse health events from smoking, and low rates of cessation, it is imperative that we increase efforts and overcome barriers to help these women quit smoking.

Background

HIV-seropositive women face high risk for infection with oncogenic human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer, but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16 is highly oncogenic but only weakly associated with HIV status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types, which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer.

Objective

We sought to assess whether the underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers.

Study design

HIV-seropositive and HIV-seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia (CIN) grade ≥3 (CIN3(+)). DNA from >40 HPV types was detected by polymerase chain reaction in cervicovaginal lavage specimens obtained at the visit at which CIN3(+) was diagnosed.

Results

HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3(+) but only 44 (29%) of 154 HIV-seropositive women with CIN3(+) (P = .01). The lower prevalence of HPV16 in CIN3(+) among HIV-seropositive women persisted after controlling for covariates (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.08-0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3(+) (OR, 1.02; 95% CI, 0.53-1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV-seropositive vs HIV-seronegative women with CIN3(+) (OR, 3.9; 95% CI, 1.3-11.8).

Conclusion

The previously demonstrated increase in CIN3(+) incidence among HIV-seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV-seropositive women.

Background

Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes.

Methods

Three urinary biomarkers of tubular impairment--neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and β-2-microglobulin (β2MG)--were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART.

Results

There were no differences between groups for NGAL or NAG, but β2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P < 0.01). History of proteinuria was associated with elevated NGAL (P < 0.01). Factors associated with elevated NAG were glomerular filtration rate <60 mL/minute, history of proteinuria, hepatitis C (P < 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated β2MG were HIV RNA >100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate <60 mL/minute (P ≤ 0.01 for all).

Conclusions

β2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIV-infected individuals at risk for renal dysfunction.