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9The Women's Interagency HIV Study (WIHS) is an ongoing long-term observational study of 3,772 women who are either infected with human immunodeficiency virus (HIV) or considered to be at risk for acquiring HIV. Since 1994, the WIHS (pronounced like "wise") has developed a large database and specimen repository that serve as resources for WIHS investigators as well as for nonaffiliated researchers working on HIVrelated or HIV coinfection issues. The purpose of this report is to update researchers on the progress of the WIHS and to provide information on WIHS resources, the methods by which they were obtained, and background for any new potential researchers interested in conducting collaborative research through shared use of these resources. BACKGROUND

In HIV-positive women, plasma HIV RNA level and CD4+ count in combination appear to have a strong and statistically interactive association with incident detection of HPV, some of which may reflect HPV reactivation (e.g., in sexually inactive women). The more moderate association between HIV coinfection and HPV persistence could partly explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women.

BACKGROUNDUniversal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODSWe randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTSA total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 personyears; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONSUniversal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.

The prevalent and incident detection of HPV16 is more weakly associated with immune status in HIV-seropositive women than that of other HPV types, suggesting that HPV16 may be better at avoiding the effects of immune surveillance, which could contribute to HPV16's strong association with cervical cancer.

Objective-To assess effects of male circumcision on female genital symptoms, and vaginal infections.Methods-HIV-negative men enrolled in a trial were randomized to immediate or delayed circumcision (control arm). Genital symptoms, BV and trichomonas were assessed in HIV-negative wives of married participants. Adjusted prevalence risk ratios (adjPRR) and 95% confidence intervals (95%CI) were assessed by multivariable log-binomial regression, intent-to-treat analyses.Results-783 wives of control and 825 wives of intervention arm men were comparable at enrollment. BV at enrollment was higher in control (38.3%) than intervention arm spouses (30.5%, p=0.001). At one year follow up, intervention arm wives reported lower rates of genital ulceration (adjPRR 0.78, 95%CI 0.63-0.97), but there were no differences in vaginal discharge or dysuria. The risk of trichomonas was reduced in intervention arm wives (adjPRR 0.52, 95%CI 0.05-0.98), as were the risks of any BV (adjPRR 0.60, 95%CI 0.38-0.94) and severe BV (PRR = 0.39, 95%CI 0.24-0.64).Conclusions-Male circumcision reduces the risk of ulceration, trichomonas and BV in female partners.

Based on a statistical analysis of 111 facilities in Africa, Asia, and Latin America, Benjamin Chi and colleagues develop a standard loss-to-follow-up (LTFU) definition that can be used by HIV antiretroviral programs worldwide.

ERVICAL CANCER SCREENING recommendations in the United States have been recently updated and now advise using an interval of 3 years between screenings in healthy women 30 years or older who have normal cytology results and who test negative for oncogenic (cancer-associated) human papillomavirus (HPV) DNA. 1,2 The recommended interval is 6 to 12 months for women with normal cytology results and detectable oncogenic HPV. If no HPV test is conducted, 3 consecutive normal annual Papanicolaou (Pap) smear results are required before the Pap smear frequency is changed to once every 2 or 3 years. Support for these recommendations comes from several large observational studies. 1-5 However, guidelines for human immunodeficiency virus (HIV)-seropositive women have not been revised since Context Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA. Objective To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results. Design, Setting, and Patients Participants were HIV-seropositive (n=855; mean age, 36 years) and HIV-seronegative (n=343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women's Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years. Main Outcome Measure The cumulative incidence of any SIL and high-grade SIL or cancer (HSILϩ) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count. Results Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/µL, 9% (95% CI, 1%-18%); with CD4 counts between 200/µL and 500/µL, 9% (95% CI, 4%-13%); and with CD4 counts greater than 500/ µL, 4% (95% CI, 1%-7%). The CIs for these estimates overlapped with those for HIVseronegative women with normal baseline cytology who were HPV-negative (3%; 95% CI, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSILϩ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIVseropositive women with CD4 counts greater than 500/µL (hazard ratio [HR], 1.2; 95% CI, 0.5-3.0), but not those with CD4 counts less than or equal to 500/µL (HR, 2.9; 95% CI, 1.2-7.1), was similar to that in HIV-seronegative women. Conclusion The similar low cumulative incidence of any SIL among HIVseronegative and HIV-seropositive women with CD4 counts greater than 500/µL and who had normal ...