Faculty Bibliography

BACKGROUND:The smoking prevalence is high (32.5%) among male providers in community health centers in Beijing, China. The majority of providers self reported that they advise patients to quit smoking, yet they have low expectations that their counseling is effective in helping patients to quit. Many have not received training on how to advise patients to quit, and half lack knowledge about nicotine replacement. These findings suggest that surveyed providers need more training in tobacco cessation services.

BACKGROUND:Male circumcision reduces the transmission of high-risk human papillomavirus (HPV) in HIV-uninfected men and their female partners. We assessed whether circumcision of HIV-infected men would reduce the transmission of high-risk HPV to their female partners. METHODS:Female partners of HIV-infected men (aged 15-49 years) in Rakai, Uganda, with CD4 counts of greater than 350 cells per mL who were randomly assigned to undergo circumcision immediately (intervention group) and after 24 months (control group) were assessed for infection with high-risk HPV. Randomisation was done in blocks of 20, stratified by community, with computer-generated random numbers. Laboratory technicians and female fieldworkers were masked to the circumcision status of male participants. The main outcome assessed in this study was the effects of circumcision of HIV-infected men on transmission of HPV to their female partners. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00124878. FINDINGS/RESULTS:474 men were assigned to the intervention group, 448 to the control group. 211 women were in consensual relationships with 193 men in the intervention group, and 171 women were in consensual unions with 155 men in the control group. High-risk HPV at the 2-year follow-up was prevalent in 88 female partners (55%) of 159 men in the intervention group and 68 (52%) of 131 female partners of men in the control group (prevalence risk ratio 1·07, 95% CI 0·86-1·32, p=0·64). Incidence of high-risk HPV over 2 years was 32·0 per 100 person-years in the female partners of men in the intervention group and 30·6 per 100 person-years in the female partners of men in the control group (incidence rate ratio 1·05, 0·77-1·43, p=0·78). No difference was noted in the clearance of genotype-specific high-risk HPV between the intervention group (196 [46%] of 424) and control group (167 [48%] of 347; rate ratio 0·96, 0·83-1·12; p=0·61). INTERPRETATION/CONCLUSIONS:Because circumcision of HIV-infected men did not affect transmission of high-risk HPV to their female partners, promotion of consistent safe sexual practices for HIV-infected men remains important. FUNDING/BACKGROUND:Bill & Melinda Gates Foundation and National Institutes of Health.

BACKGROUND:Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men. METHODS:In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878. FINDINGS/RESULTS:During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60-0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63-0·93, p=0·008). INTERPRETATION/CONCLUSIONS:Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important. FUNDING/BACKGROUND:The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

Male circumcision (MC) reduces penile high-risk human papillomavirus (HR-HPV) on the coronal sulcus and urethra. HR-HPV varies by anatomic site, and it is unknown whether MC decreases HR-HPV on the penile shaft. We assessed the efficacy of MC to reduce HR-HPV on the penile shaft and compared it to known efficacy of MC to reduce HR-HPV on the coronal sulcus. HIV-negative men randomized to receive immediate circumcision (intervention) or circumcision delayed for 24 months (control) were evaluated for HR-HPV at 12 months postenrollment using the Roche HPV Linear Array assay. Among swabs with detectable β-globin or HPV, year 1 HR-HPV prevalence on the coronal sulcus was 21.5% in the intervention arm and 36.3% in the control arm men [adjusted prevalence risk ratios (PRRs) = 0.57, 95% CI 0.39-0.84, p = 0.005]. On the shaft, year 1 HR-HPV prevalence was 15.5% in the intervention and 23.8% in the control arm (adjusted PRR = 0.66, 95% CI 0.39-1.12, p = 0.12). Efficacy of MC to reduce HR-HPV on the shaft was similar to efficacy on the coronal sulcus (p = 0.52). In a sensitivity analysis in which swabs without detectable β-globin or HPV were included as HPV negative, prevalence of HR-HPV on the shaft was lower in the intervention arm (7.8%) than control arm (13.6%; PRR 0.57, 95% CI 0.33-0.99, p < 0.05). HR-HPV was more frequently detected on the coronal sulcus than penile shaft among uncircumcised men (36.3% vs. 23.8%, respectively, p = 0.02) and circumcised men (21.5% vs. 15.5%, respectively, p = 0.24). MC reduced HR-HPV prevalence on both the coronal sulcus and shaft.

OBJECTIVE:To assess the diagnostic accuracy of the urine lipoarabinomannan (LAM) test among ambulatory HIV-infected persons. DESIGN/METHODS:Cross-sectional. METHODS:HIV-infected persons consecutively presenting to the HIV Clinic at Tembisa Main Clinic in Ekhuruleni, South Africa, were screened for symptoms of tuberculosis (TB) and asked to provide sputum and blood samples for smears for acid-fast bacilli and mycobacterial culture and a urine specimen for a LAM enzyme-linked immunosorbent assay. Fine needle aspirates were obtained from participants with enlarged lymph nodes and sent for histopathology. Nonpregnant participants underwent chest x-ray. RESULTS:: Four hundred twenty-two HIV-infected participants were enrolled with median age 37 years (interquartile range: 31-44 years), median CD4+ T-cell count 215 cells per microliter (interquartile range: 107-347 cells/μL), and 212 (50%) receiving antiretroviral therapy. Thirty (7%) had active TB: 18 with only pulmonary TB, 5 with only extrapulmonary TB, and 7 with both pulmonary TB and extrapulmonary TB. Twenty-seven percent [95% confidence interval (CI): 12% to 48%] of TB cases were sputum acid-fast bacilli positive. The sensitivity and specificity of the urine LAM compared with the gold standard of positive bacteriology or histopathology were 32% (95% CI: 16% to 52%) and 98% (95% CI: 96% to 99%), respectively. Urine LAM had higher sensitivity in TB cases with higher bacillary burdens, though these differences were not statistically significant. CONCLUSIONS:The sensitivity of urine LAM testing is inadequate to replace mycobacterial culture. In contrast to prior research on the urine LAM, this study was conducted among less sick, ambulatory HIV-infected patients presenting for routine care.

BACKGROUND:Human immunodeficiency virus (HIV) and tuberculosis (TB) are among the leading causes of death among women of reproductive age worldwide. TB is a significant cause of maternal morbidity. Detection of TB during pregnancy could provide substantial benefits to women and their children. METHODS:This was a cross-sectional implementation research study of integrating active TB case-finding into existing antenatal and prevention of mother-to-child transmission services in six clinics in Soweto, South Africa. All pregnant women 18 years of age or older presenting for routine care to these public clinics were screened for symptoms of active TB, cough for 2 weeks or longer, sputum production, fevers, night sweats, or weight loss, regardless of their HIV status. Participants with any symptom of active TB were asked to provide a sputum specimen for smear microscopy, mycobacterial culture and drug-susceptibility testing. RESULTS:Between December 2008 and July 2009, 3963 pregnant women were enrolled and screened for TB, of whom 1454 (36.7%) were HIV-seropositive. Any symptom of TB was reported by 23.1% of HIV-seropositive and 13.8% of HIV-seronegative women (P < 0.01). Active pulmonary TB was diagnosed in 10 of 1454 HIV-seropositve women (688 per 100,000) and 5 of 2483 HIV-seronegative women (201 per 100,000, P = 0.03). The median CD4⁺ T-cell count among HIV-seropositive women with TB was similar to that of HIV-seropositive women without TB (352 versus 333 cells/μL, P = 0.85). CONCLUSIONS:There is a high burden of active TB among HIV-seropositive pregnant women. TB screening and provision of isoniazid preventive therapy and antiretroviral therapy should be integrated with prevention of mother-to-child transmission services.