Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exi... more Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exist characterizing precursor abnormal anal cytology incidence. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in four U.S. cities. At baseline and annually thereafter, each completed a behavioral questionnaire, and providers collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. Among 243 participants with negative baseline anal cytology, 37% developed abnormal cytology (incidence rate 13.9/100 person-years [p-y], 95% confidence interval [CI] 11.3 - 16.9) over a median 2.1 years of follow-up. Rates among men having sex with men, women, and men having sex with women, were 17.9 p-y (CI: 13.9 - 22.7), 9.4 p-y (CI: 5.6 - 14.9), 8.9 p-y (CI: 4.8 - 15.6), respectively. In multivariable analysis, number of persistent high-risk HPV (HR) types (adjusted hazards ratio [adjHR] 1.17, CI: 1.01 - 1.36), persistent HR-HPV types except 16 or 18 ([adjHR] 2.46, CI 1.31 - 4.60), and persistent types 16 or 18 (adjHR 3.90, CI: 1.78 - 8.54) remained associated with incident abnormalities. Abnormal anal cytology incidence was high and more likely to develop among persons with persistent HR-HPV.
... New York and Texas routinely test "high risk"inmates (Maruschak). ... was o... more ... New York and Texas routinely test "high risk"inmates (Maruschak). ... was offered to them, and test acceptance was correlated with a history of exchanging sex for drugs or money, as well as withconviction for a drug-related crime (Cotton-Oldenburg, Jordan, Martin, Sadowski, 1999 ...
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002)
To compare Papanicolaou (Pap) smear readings to visual inspection with acetic acid (VIA) findings... more To compare Papanicolaou (Pap) smear readings to visual inspection with acetic acid (VIA) findings among HIV-infected women in Phnom Penh, Cambodia. A total of 304 HIV-infected women presenting to the women's clinic at the Community Resource Center in Phnom Penh, Cambodia, were screened for cervical cancer by both Pap smear and VIA. The results of the 2 tests were compared. Complete data were available on 293 women. In all, 55 (19%) women screened positive on VIA; 25 (8.5%) women screened positive by Pap. Visual inspection with acetic acid detected 18 of the 25 patients with abnormal cytology and was normal in 7 women with abnormal cytology. A total of 37 (67%) women with positive VIA were negative by cytology. Our study shows a reasonable correlation between VIA and Pap smear, with VIA detecting more abnormalities than cytology. In the absence of Pap smear availability, VIA may be a reasonable cervical cancer screening method for HIV-infected women in Cambodia.
To determine which mucosal immunization routes may be optimal for induction of antibodies in the ... more To determine which mucosal immunization routes may be optimal for induction of antibodies in the rectum and female genital tract, groups of women were immunized a total of three times either orally, rectally, or vaginally with a cholera vaccine containing killed Vibrio cholerae cells and the recombinant cholera toxin B (CTB) subunit. Systemic and mucosal antibody responses were assessed at 2-week intervals by quantitation of CTB-specific antibodies in serum and in secretions collected directly from mucosal surfaces of the oral cavity, rectum, cervix, and vagina with absorbent wicks. The three immunization routes increased levels of specific immunoglobulin G (IgG) in serum and specific IgA in saliva to similar extents. Rectal immunization was superior to other routes for inducing high levels of specific IgA and IgG in rectal secretions but was least effective for generating antibodies in female genital tract secretions. Only vaginal immunization significantly increased both specific ...
The second wave of the HIV epidemic, which increasingly affects injection drug users, women, and ... more The second wave of the HIV epidemic, which increasingly affects injection drug users, women, and minorities, necessitates the development of primary care HIV services so that these individuals may benefit from new therapies. The ability to dramatically decrease vertical transmission of HIV from mother to child with antiretroviral therapy is encouraging. Better understanding of HIV pathogenesis, disease progression, antiviral therapy, and opportunistic infection prophylaxis are leading to more effective therapy and prevention. Clinical trials are ongoing to assess the efficacy of protease inhibitors in combination with nucleoside analog antiretroviral therapy to provide long term viral suppression and alter the natural history of HIV. Prophylaxis of pneumocystis, toxoplasma, MAC, TB, and invasive fungal infections is cost effective and leads to improved quality of life.
Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical c... more Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach wa...
HIV infection and associated immunodeficiency are known to alter the course of human papillomavir... more HIV infection and associated immunodeficiency are known to alter the course of human papillomavirus (HPV) infections and of associated diseases. This study investigated the association between HIV and HPV and genital warts. HPV testing and physical examinations were performed in two large prospective studies: the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS). Statistical methods incorporating dependencies of longitudinal data were used to examine the relationship between HIV and HPV and genital warts. A total of 1008 HIV-seronegative and 2930 HIV-seropositive women were enrolled in the two studies. The prevalence of HPV 6 or 11 was 5.6 times higher in HIV-seropositive women in the WIHS and 3.6 times higher in the HERS. Genital wart prevalence increased by a factor of 3.2 in the WIHS and 2.7 in the HERS in HIV-seropositive women. In the WIHS, infection with HPV type 6 or 11, in comparison with no HPV infection, was associated with odds of genital wart prevalence of 5.1 (95% CI: 2.9-8.8), 8.8 (95% CI: 6.1-12.8), and 12.8 (95% CI: 8.8-18.8) in HIV-seronegative women, HIV-seropositive women with > or =201 CD4 cells/microl, and HIV-seropositive women with < or =200 CD4 cells/microl, respectively. In the HERS, infection with HPV type 6 or 11 was associated with odds of 2.7 (95% CI: 1.6-4.6), 4.9 (95% CI: 3.2-7.7), and 5.3 (95% CI: 3.3-8.5) in these same groups. Other HPV types showed a similar dose-response relation, but of substantially lower magnitude and statistical significance. HIV infection and immunodeficiency synergistically modified the relation between HPV 6 or 11 infection and genital wart prevalence.
Background: Women infected with HIV face a combination of health threats that include compromised... more Background: Women infected with HIV face a combination of health threats that include compromised nutrition and adverse gy- necological conditions. This relation among HIV, nutrition, and gynecological conditions is complex and has rarely been investi- gated. Objective: Our objective was to investigate nutritional biomarkers associatedwithseveralgynecologicalconditionsamongUSwomen with or at risk of HIV infection. Design:Dataon369HIV-infectedand184HIV-uninfectedwomen with both nutritional and gynecological outcomes were
Combination antiretroviral therapy is recommended for pregnant women with human immunodeficiency ... more Combination antiretroviral therapy is recommended for pregnant women with human immunodeficiency virus (HIV) to decrease perinatal transmission. Treatment can cause mitochondrial dysfunction, leading to liver damage and acidosis. Early diagnosis is essential to improve outcome. A multiparous woman with HIV-1 taking combination antiretroviral therapy presented with pneumonia at 28 weeks of gestation. Once treated, she improved clinically. However, nonreassuring fetal testing prompted further assessment, revealing maternal metabolic acidosis and transaminitis. Drug-induced hepatotoxicity was diagnosed, and combination antiretroviral therapy was discontinued. Fetal testing and maternal lab abnormalities subsequently improved. Usual manifestations of hepatotoxicity and acidosis secondary to combination antiretroviral therapy include nausea, vomiting, and jaundice. In this case, nonreassuring fetal testing led to the diagnosis of hepatic dysfunction. Abnormal fetal testing can result from drug-related toxicity and warrants prompt assessment.
To evaluate the presence of and estimate risk factors for reactivation of latent high-risk human ... more To evaluate the presence of and estimate risk factors for reactivation of latent high-risk human papillomavirus (HPV) cervical infection in human immunodeficiency virus (HIV)-infected and HIV-uninfected women. Data from 898 women in the HIV Epidemiology Research Study (HERS) were used to evaluate cervical HPV latency and reactivation. Prior exposure to HPV types (16, 18, 31, 35, and 45) was determined by serologic testing at enrollment, and cervical shedding of HPV was detected by polymerase chain reaction at 6-month intervals. Human papillomavirus cervical shedding and sexual history were used to estimate rates of reactivation and recurrence. Repeated measures survival analysis was used to estimate hazard ratios and 95% confidence intervals for reactivation and recurrence. Rates of total HPV shedding (recurrence and reactivation) during follow-up were assessed by HIV status and rate ratios were calculated. Reactivation of latent HPV infections was observed in HIV-infected women, but few reactivation events were identified in HIV-uninfected women. Factors consistently associated with reactivation in HIV-infected women included CD4 count less than 200/mm and age younger than 35 years. Women infected with HIV had 1.8 to 8.2 times higher rates of viral shedding (reactivation plus recurrence) compared with HIV-uninfected women. Women with a history of cervical HPV infection may be at risk of reactivation of latent viral infection even in the absence of sexual activity, and this risk is higher in women with HIV infection. II.
To describe outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women with HI... more To describe outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women with HIV. Women in two prospective cohort studies, the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS), were followed every 6 months after treatment of CIN using human papillomavirus (HPV) testing and cytology with colposcopy as indicated. Identification of CIN or a squamous intraepithelial lesion (SIL) within 6 months was defined as treatment failure and later disease as recurrence. Follow-up was available for 170 HIV-seropositive and 15 HIV-seronegative women. Treatment failed in 84 (45%) women (79 HIV seropositive and 5 HIV seronegative). Failure was more likely in women with lower CD4 counts (CD4 < 200 cells/microL: odds ratio [OR] = 2.96; 95% CI = 1.4-6.2) and detectable HPV DNA (OR 8.20; 95% CI = 1.8-37.4; p = .01). After successful treatment, recurrence-free probabilities at 1,2, 3, and 5 years were .79, .64, .49, and .34, respectively. HIV-seronegative women were less likely to recur than HIV-seropositive women (p = .03). In multivariable analysis of HIV-positive women, recurrence was more likely among women treated for CIN 2,3 (hazard ratio [HR] = 2.4; 95% CI = 1.4-4.8), those with CD4 count of less than 200 cells/microL (HR = 2.9; 95% CI = 1.3-6.5) and those with HPV after treatment (HR 2.9; 95% CI = 1.4-6.1); oncogenic HPV was more strongly associated with recurrence than nononcogenic HPV (p(trend) = .009). Most failures and recurrences were low grade, but one adenocarcinoma was diagnosed 4.2 years after therapy for CIN 1. Treatment failure and recurrence are common in women with HIV but are usually low grade.
Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exi... more Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exist characterizing precursor abnormal anal cytology incidence. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in four U.S. cities. At baseline and annually thereafter, each completed a behavioral questionnaire, and providers collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. Among 243 participants with negative baseline anal cytology, 37% developed abnormal cytology (incidence rate 13.9/100 person-years [p-y], 95% confidence interval [CI] 11.3 - 16.9) over a median 2.1 years of follow-up. Rates among men having sex with men, women, and men having sex with women, were 17.9 p-y (CI: 13.9 - 22.7), 9.4 p-y (CI: 5.6 - 14.9), 8.9 p-y (CI: 4.8 - 15.6), respectively. In multivariable analysis, number of persistent high-risk HPV (HR) types (adjusted hazards ratio [adjHR] 1.17, CI: 1.01 - 1.36), persistent HR-HPV types except 16 or 18 ([adjHR] 2.46, CI 1.31 - 4.60), and persistent types 16 or 18 (adjHR 3.90, CI: 1.78 - 8.54) remained associated with incident abnormalities. Abnormal anal cytology incidence was high and more likely to develop among persons with persistent HR-HPV.
... New York and Texas routinely test "high risk"inmates (Maruschak). ... was o... more ... New York and Texas routinely test "high risk"inmates (Maruschak). ... was offered to them, and test acceptance was correlated with a history of exchanging sex for drugs or money, as well as withconviction for a drug-related crime (Cotton-Oldenburg, Jordan, Martin, Sadowski, 1999 ...
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002)
To compare Papanicolaou (Pap) smear readings to visual inspection with acetic acid (VIA) findings... more To compare Papanicolaou (Pap) smear readings to visual inspection with acetic acid (VIA) findings among HIV-infected women in Phnom Penh, Cambodia. A total of 304 HIV-infected women presenting to the women's clinic at the Community Resource Center in Phnom Penh, Cambodia, were screened for cervical cancer by both Pap smear and VIA. The results of the 2 tests were compared. Complete data were available on 293 women. In all, 55 (19%) women screened positive on VIA; 25 (8.5%) women screened positive by Pap. Visual inspection with acetic acid detected 18 of the 25 patients with abnormal cytology and was normal in 7 women with abnormal cytology. A total of 37 (67%) women with positive VIA were negative by cytology. Our study shows a reasonable correlation between VIA and Pap smear, with VIA detecting more abnormalities than cytology. In the absence of Pap smear availability, VIA may be a reasonable cervical cancer screening method for HIV-infected women in Cambodia.
To determine which mucosal immunization routes may be optimal for induction of antibodies in the ... more To determine which mucosal immunization routes may be optimal for induction of antibodies in the rectum and female genital tract, groups of women were immunized a total of three times either orally, rectally, or vaginally with a cholera vaccine containing killed Vibrio cholerae cells and the recombinant cholera toxin B (CTB) subunit. Systemic and mucosal antibody responses were assessed at 2-week intervals by quantitation of CTB-specific antibodies in serum and in secretions collected directly from mucosal surfaces of the oral cavity, rectum, cervix, and vagina with absorbent wicks. The three immunization routes increased levels of specific immunoglobulin G (IgG) in serum and specific IgA in saliva to similar extents. Rectal immunization was superior to other routes for inducing high levels of specific IgA and IgG in rectal secretions but was least effective for generating antibodies in female genital tract secretions. Only vaginal immunization significantly increased both specific ...
The second wave of the HIV epidemic, which increasingly affects injection drug users, women, and ... more The second wave of the HIV epidemic, which increasingly affects injection drug users, women, and minorities, necessitates the development of primary care HIV services so that these individuals may benefit from new therapies. The ability to dramatically decrease vertical transmission of HIV from mother to child with antiretroviral therapy is encouraging. Better understanding of HIV pathogenesis, disease progression, antiviral therapy, and opportunistic infection prophylaxis are leading to more effective therapy and prevention. Clinical trials are ongoing to assess the efficacy of protease inhibitors in combination with nucleoside analog antiretroviral therapy to provide long term viral suppression and alter the natural history of HIV. Prophylaxis of pneumocystis, toxoplasma, MAC, TB, and invasive fungal infections is cost effective and leads to improved quality of life.
Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical c... more Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach wa...
HIV infection and associated immunodeficiency are known to alter the course of human papillomavir... more HIV infection and associated immunodeficiency are known to alter the course of human papillomavirus (HPV) infections and of associated diseases. This study investigated the association between HIV and HPV and genital warts. HPV testing and physical examinations were performed in two large prospective studies: the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS). Statistical methods incorporating dependencies of longitudinal data were used to examine the relationship between HIV and HPV and genital warts. A total of 1008 HIV-seronegative and 2930 HIV-seropositive women were enrolled in the two studies. The prevalence of HPV 6 or 11 was 5.6 times higher in HIV-seropositive women in the WIHS and 3.6 times higher in the HERS. Genital wart prevalence increased by a factor of 3.2 in the WIHS and 2.7 in the HERS in HIV-seropositive women. In the WIHS, infection with HPV type 6 or 11, in comparison with no HPV infection, was associated with odds of genital wart prevalence of 5.1 (95% CI: 2.9-8.8), 8.8 (95% CI: 6.1-12.8), and 12.8 (95% CI: 8.8-18.8) in HIV-seronegative women, HIV-seropositive women with > or =201 CD4 cells/microl, and HIV-seropositive women with < or =200 CD4 cells/microl, respectively. In the HERS, infection with HPV type 6 or 11 was associated with odds of 2.7 (95% CI: 1.6-4.6), 4.9 (95% CI: 3.2-7.7), and 5.3 (95% CI: 3.3-8.5) in these same groups. Other HPV types showed a similar dose-response relation, but of substantially lower magnitude and statistical significance. HIV infection and immunodeficiency synergistically modified the relation between HPV 6 or 11 infection and genital wart prevalence.
Background: Women infected with HIV face a combination of health threats that include compromised... more Background: Women infected with HIV face a combination of health threats that include compromised nutrition and adverse gy- necological conditions. This relation among HIV, nutrition, and gynecological conditions is complex and has rarely been investi- gated. Objective: Our objective was to investigate nutritional biomarkers associatedwithseveralgynecologicalconditionsamongUSwomen with or at risk of HIV infection. Design:Dataon369HIV-infectedand184HIV-uninfectedwomen with both nutritional and gynecological outcomes were
Combination antiretroviral therapy is recommended for pregnant women with human immunodeficiency ... more Combination antiretroviral therapy is recommended for pregnant women with human immunodeficiency virus (HIV) to decrease perinatal transmission. Treatment can cause mitochondrial dysfunction, leading to liver damage and acidosis. Early diagnosis is essential to improve outcome. A multiparous woman with HIV-1 taking combination antiretroviral therapy presented with pneumonia at 28 weeks of gestation. Once treated, she improved clinically. However, nonreassuring fetal testing prompted further assessment, revealing maternal metabolic acidosis and transaminitis. Drug-induced hepatotoxicity was diagnosed, and combination antiretroviral therapy was discontinued. Fetal testing and maternal lab abnormalities subsequently improved. Usual manifestations of hepatotoxicity and acidosis secondary to combination antiretroviral therapy include nausea, vomiting, and jaundice. In this case, nonreassuring fetal testing led to the diagnosis of hepatic dysfunction. Abnormal fetal testing can result from drug-related toxicity and warrants prompt assessment.
To evaluate the presence of and estimate risk factors for reactivation of latent high-risk human ... more To evaluate the presence of and estimate risk factors for reactivation of latent high-risk human papillomavirus (HPV) cervical infection in human immunodeficiency virus (HIV)-infected and HIV-uninfected women. Data from 898 women in the HIV Epidemiology Research Study (HERS) were used to evaluate cervical HPV latency and reactivation. Prior exposure to HPV types (16, 18, 31, 35, and 45) was determined by serologic testing at enrollment, and cervical shedding of HPV was detected by polymerase chain reaction at 6-month intervals. Human papillomavirus cervical shedding and sexual history were used to estimate rates of reactivation and recurrence. Repeated measures survival analysis was used to estimate hazard ratios and 95% confidence intervals for reactivation and recurrence. Rates of total HPV shedding (recurrence and reactivation) during follow-up were assessed by HIV status and rate ratios were calculated. Reactivation of latent HPV infections was observed in HIV-infected women, but few reactivation events were identified in HIV-uninfected women. Factors consistently associated with reactivation in HIV-infected women included CD4 count less than 200/mm and age younger than 35 years. Women infected with HIV had 1.8 to 8.2 times higher rates of viral shedding (reactivation plus recurrence) compared with HIV-uninfected women. Women with a history of cervical HPV infection may be at risk of reactivation of latent viral infection even in the absence of sexual activity, and this risk is higher in women with HIV infection. II.
To describe outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women with HI... more To describe outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women with HIV. Women in two prospective cohort studies, the Women's Interagency HIV Study (WIHS) and the HIV Epidemiology Research Study (HERS), were followed every 6 months after treatment of CIN using human papillomavirus (HPV) testing and cytology with colposcopy as indicated. Identification of CIN or a squamous intraepithelial lesion (SIL) within 6 months was defined as treatment failure and later disease as recurrence. Follow-up was available for 170 HIV-seropositive and 15 HIV-seronegative women. Treatment failed in 84 (45%) women (79 HIV seropositive and 5 HIV seronegative). Failure was more likely in women with lower CD4 counts (CD4 < 200 cells/microL: odds ratio [OR] = 2.96; 95% CI = 1.4-6.2) and detectable HPV DNA (OR 8.20; 95% CI = 1.8-37.4; p = .01). After successful treatment, recurrence-free probabilities at 1,2, 3, and 5 years were .79, .64, .49, and .34, respectively. HIV-seronegative women were less likely to recur than HIV-seropositive women (p = .03). In multivariable analysis of HIV-positive women, recurrence was more likely among women treated for CIN 2,3 (hazard ratio [HR] = 2.4; 95% CI = 1.4-4.8), those with CD4 count of less than 200 cells/microL (HR = 2.9; 95% CI = 1.3-6.5) and those with HPV after treatment (HR 2.9; 95% CI = 1.4-6.1); oncogenic HPV was more strongly associated with recurrence than nononcogenic HPV (p(trend) = .009). Most failures and recurrences were low grade, but one adenocarcinoma was diagnosed 4.2 years after therapy for CIN 1. Treatment failure and recurrence are common in women with HIV but are usually low grade.
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Papers by Susan Cu-Uvin