Tedd V. Ellerbrock

Human Papillomavirus Infection in Women Infected with the Human Immunodeficiency Virus

Background Among women infected with the human immunodeficiency virus (HIV), there is a high prevalence of human papillomavirus (HPV) infections. However, little is known about the natural history of HPV infections in HIV-seropositive women, and persistent HPV infections may explain the increased risk of cervical squamous intraepithelial lesions and invasive cervical cancer in HIV-seropositive women. Methods A total of 220 HIV-seropositive and 231 HIV-seronegative women in the New York City area were evaluated at two or more semiannual gynecologic examinations that included a Pap test, a test for HPV DNA, and colposcopy. Results HPV DNA was detected at the initial examination in 56 percent of the HIV-seropositive and 31 percent of the HIV-seronegative women. After four examinations, the cumulative prevalence of HPV infection was 83 percent in the seropositive women and 62 percent in the seronegative women (P<0.001). Persistent HPV infections were found in 24 percent of the seropositive women but in only 4...

Correlation of Human Immunodeficiency Virus Type 1 RNA Levels in Blood and the Female Genital Tract

In this study, the correlations of human immunodeficiency virus type 1 (HIV-1) RNA levels in blood plasma, vaginal secretions, and cervical mucus of 52 HIV-1-infected women were determined. The amount of cell-free HIV-1 RNA in blood plasma was correlated with that in vaginal secretions (Spearmans rank correlation coefficient (r) = 0.64, P<.001). In both blood plasma and vaginal secretions, the amounts of cell-free and cell-associated HIV-1 RNA were highly correlated (r=0.76, P<.01 and r=0.85, P<.01, respectively). Cell-free HIV-1 RNA levels in blood plasma and vaginal secretions were negatively correlated with CD4+ T lymphocyte count (r=-0.44, P<.01 and r=-0.40, P<.01, respectively). Similar to the effect observed in blood plasma, initiation of antiretroviral therapy significantly reduced the amount of HIV-1 RNA in vaginal secretions. These findings suggest that factors that lower blood plasma virus load may also reduce the risk of perinatal and female-to-male heterosexual transmission by lowering vaginal virus load.

Virologic and immunologic outcomes and programmatic challenges of an antiretroviral treatment pilot project in Abidjan, Côte d'Ivoire.

BackgroundIn Côte dIvoire, a pilot project was developed by UNAIDS and the Ministry of Health to improve access to AIDS care, including antiretroviral therapy, for adults and children infected with HIV. This evaluation of the project is the first to provide results of a large number of HIV-infected patients receiving antiretroviral therapy in West Africa. MethodsWe evaluated records of persons who presented for care from August 1998 to August 2000 at six accredited centers in Abidjan. Patients were treated with two nucleoside reverse transcriptase inhibitors (2NRTI) or highly active antiretroviral therapy (HAART). ResultsOf 2878 patients who were screened, 2351 (83%) were HIV-infected and eligible (CD4 T lymphocyte count < 500 × 106 cells/l or plasma HIV-RNA level > 10 000 copies/ml) for antiretroviral therapy. Of those who were eligible, 81% were symptomatic, 63% had a CD4 cell count < 200 × 106 cells/l, 12% had previously taken antiretroviral drugs, and 56% returned to the clinic for follow-up. Of the patients screened, 768 (27%) were started on antiretroviral therapy, including 450 on HAART, 296 on 2NRTI, and 22 on other regimens. We analyzed data from 480 HIV-1-infected adults, who were naive to therapy, were prescribed HAART or 2NRTI, and had at least one clinic visit after starting therapy. In an intent-to-treat analysis of patients who received HAART, the estimated plasma HIV-1 RNA level was approximately 1.9 log10 copies/ml (80-fold) lower, while estimated CD4 cell count was > 100 × 106 cells/l higher than baseline values, after 1 year of therapy. Approximately 25% of adults on 2NRTI and 50% of those on HAART had < 200 copies/ml, after 1 year of therapy. The probability of an adverse event occurring within 6 months after starting therapy was 0.20. The probability of survival for at least 1 year was 0.84 (95% confidence interval, 0.80–0.89). ConclusionAfter starting antiretroviral therapy, these HIV-1-infected patients in West Africa had similar virologic and immunologic outcomes, probability of an adverse event, and estimated survival, as patients enrolled in clinical trials in the USA and Europe. However, only one-third of eligible patients received therapy, highlighting the importance of providing adequate education and support for initiating and adhering to therapy in this and similar programmes.

HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: a prospective cohort study

BACKGROUNDnInformation about vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia in women infected with HIV-1 is needed to develop guidelines for clinical care. Our aim was to investigate the incidence of these lesions in HIV-1-positive and HIV-1-negative women and to examine risk factors for disease.nnnMETHODSnIn a prospective cohort study, 925 women had a gynaecological examination twice yearly-including colposcopy and tests for human papillomavirus DNA in cervicovaginal lavage-for a median follow-up of 3.2 years (IQR 0.98-4.87).nnnFINDINGSnVulvovaginal and perianal condylomata acuminata or intraepithelial neoplasia were present in 30 (6%) of 481 HIV-1-positive and four (1%) of 437 HIV-1-negative women (p<0.0001) at enrollment. Women without lesions at enrollment were included in an incidence analysis. 33 (9%) of 385 HIV-1-positive and two (1%) of 341 HIV-1-negative women developed vulvovaginal or perianal lesions, resulting in an incidence of 2.6 and 0.16 cases per 100 person-years, respectively (relative risk 16, 95% CI 12.9-20.5; p < 0.0001). Risk factors for incident lesions included HIV-1 infection (p = 0.013), human papillomavirus infection (p=0.0013), lower CD4 T lymphocyte count (p = 0.0395), and history of frequent injection of drugs (p=0.0199).nnnINTERPRETATIONnOur results suggest that HIV-1-positive women are at increased risk of development of invasive vulvar carcinoma. Thus, we recommend that, as part of every gynaecological examination, HIV-1-positive women should have a thorough inspection of the vulva and perianal region, and women with abnormalities-except for typical, exophytic condylomata acuminata-should undergo colposcopy and biopsy.

Heterosexually transmitted human immunodeficiency virus infection among pregnant women in a rural Florida community.

BACKGROUNDnIn the United States, an increasing proportion of women infected with the human immunodeficiency virus (HIV) live in nonmetropolitan areas. Little is known, however, about the risk factors for HIV transmission in women outside large cities.nnnMETHODSnWe interviewed and tested 1082 (99.8 percent) of 1084 consecutive pregnant women who registered for prenatal care at a public health clinic in western Palm Beach County, Florida. This rural agricultural area of about 36,000 people is known to have a high prevalence of HIV infection.nnnRESULTSnThe seroprevalence of HIV was 5.1 percent (52 of 1011 women). Black women who were neither Haitian nor Hispanic had the highest rate of infection (8.3 percent [48 of 575]). Only 4 of 1009 women (0.4 percent) reported ever injecting drugs, and the 4 were HIV-seronegative; however, 14 of 43 users of crack cocaine (33 percent) had HIV infection. At prenatal registration, 131 of 983 women (13 percent) tested positive for gonorrhea, chlamydial infection, or syphilis. By multivariate logistic-regression analysis, HIV infection was found to be independently associated with having used crack cocaine (odds ratio, 3.3; P < 0.001), having had more than two sexual partners (odds ratio, 4.6; P < 0.001), being black but neither Hispanic nor Haitian (odds ratio, 11; P < 0.001), having had sexual intercourse with a high-risk partner (odds ratio, 5.6; P < 0.001), and testing positive for syphilis (odds ratio, 3.1; P = 0.015). Nevertheless, 11 of the 52 HIV-infected women (21 percent) reported a total of only two to five sexual partners and no known high-risk partners, had never used crack cocaine, and had no positive tests for sexually transmitted disease.nnnCONCLUSIONSnIn the rural community we studied, most of the women with HIV infection acquired it through heterosexual contact. The increasing seroprevalence of HIV and the increasing incidence of syphilis and use of crack cocaine mean that other women may be at similar risk of acquiring heterosexually transmitted HIV infection.

Increased prevalence of vulvovaginal condyloma and vulvar intraepithelial neoplasia in women infected with the human immunodeficiency virus

Objective To compare the prevalence of human papilloma-virus (HPV)-associated vulvovaginal lesions in human immunodeficiency virus (HIV)-positive and HIV-negative women. Methods For this cross-sectional study, all participants received a complete gynecologic examination including colposcopic evaluation and a structured interview about sociodemographic characteristics and risk factors for vulvovaginal disease. In addition, HPV DNA was assayed for in cervicovaginal lavages using polymerase chain reaction. Results Vulvar and/or vaginal condyloma acuminata were detected in 22 of 396 (5.6%) HIV-positive and in 3 of 375 (0.8%) HIV-negative women (odds ratio [OR] 7.3, P < .001). High-grade vulvar intraepithelial neoplasia (VIN) was present in two of the HIV-positive and none of the HIV-negative women. Human immunodeficiency virus-positive women with condyloma or VIN were significantly more likely to have cervical intraepithelial neoplasia (33%) than those without vulvovaginal lesions (17%) (OR 2.9, 95% confidence interval [CI] 1.1, 74). In multivariate logistic regression analysis, both HIV seropositivity (adjusted OR 5.3, 95% CI 1.3, 35.3) and HPV infection (adjusted OR 6.1, 95% CI 1.7, 39.4) were associated with vulvovaginal condyloma. Conclusion The prevalence of vulvovaginal condyloma was increased in HIV-positive women even when controlling for HPV infection. Human papillomavirus-associated disease was more likely to be multicentric and involve the vulva, vagina, and cervix in HIV-positive than HIV-negative women. Detection of high-grade VIN in two of the HIV positive women suggests that they may also be at risk for developing invasive vulvar carcinoma.

Prevalence of anal human papillomavirus infection and anal cytologic abnormalities in HIV-seropositive women

Objective: To determine the prevalence of anal human papillomavirus (HPV) infections and anal cytologic abnormalities in HIV‐seropositive and HIV‐seronegative women. Design: This cross‐sectional study of a cohort of women with known HIV serostatus involved a standardized interview and a gynecologic examination, including a cytologic evaluation of the cervix and anus. Anal swabs were tested for HPV DNA using the Hybrid Capture assay. Setting: Two HIV/AIDS clinics, a sexually transmitted disease clinic, a methadone clinic and women enrolled in a study of HIV heterosexual transmission in the greater New York City metropolitan area. Patients: One hundred and two HIV‐seropositive and 96 HIV‐seronegative women were selected from an ongoing study of the gynecologic manifestations of HIV infection. Main outcome measures: Detection of anal HPV DNA and anal cytologic abnormalities. Results: Anal cytologic abnormalities were detected in 27 (26%) of the 102 HIV‐seropositive women and in six (7%) of 96 HIV‐seronegative women. Five (5%) of the anal smears from the HIV‐seropositive women and one (1%) from the HIVseronegative women had low‐grade anal intra‐epithelial neoplasia. The remainder of the anal cytologic abnormalities were classified as mild squamous cytologic atypia. HPV DNA was detected in 30 (29%) of 102 HIV‐seropositive and two (2%) of 96 HIVseronegative women. Of the 33 patients with anal cytologic abnormalities, 19 (58%) had anal HPV DNA detected as compared to 1 3 (8%) of 160 women without cytologic abnormalities (P< 0.001). In a multivariate logistic regression analysis, HIVseropositivity was tound to be an independent risk tactor for both anal HPV infection and anal cytologic abnormalities and the strength of the association was greater in women with lower CD4+ T‐lymphocyte counts. Conclusion: The prevalence of both anal cytologic abnormalities and anal HPV infection are significantly increased in HIV‐seropositive women.

Characteristics of menstruation in women infected with human immunodeficiency virus.

Objective To determine the characteristics of menstruation in women infected with human immunodeficiency virus (HIV) and the impact of immunosuppression on menstruation in HIV-infected women. Methods In this cross-sectional study, 197 HIV-infected and 189 HIV-uninfected women were interviewed about menstruation and abnormal vaginal bleeding during the previous 12 months. Information was also obtained about CD4+ T-lymphocyte levels of HIV-infected women and other factors, including drug use and weight loss, that might affect menstruation. Results The number and duration of menses in HIV-infected women were not significantly different from those of uninfected women. During a 12-month period, 154 (78%) of 197 HIV-infected women and 150 (80%) of 188 uninfected women had 10–14 menses (P = .74). The proportions of women in the two groups with intermenstrual bleeding, postcoital bleeding, or no bleeding were also similar. In HIV-infected women, menstruation and the prevalence of abnormal vaginal bleeding were not significantly different by CD4+ T-lymphocyte level. By multiple logistic regression analysis, neither HIV infection nor CD4+ T-lymphocyte level less than 200 cells/μL was associated with intermenstrual bleeding, postcoital bleeding, or no bleeding. Conclusion The results of this study suggest that neither HIV infection nor immunosuppression has a clinically relevant effect on menstruation or other vaginal bleeding. Most HIV-infected women menstruate about every 25–35 days, suggesting monthly ovulation and an intact hypothalamic-pituitary-ovarian axis.

Cellular Replication of Human Immunodeficiency Virus Type 1 Occurs in Vaginal Secretions

Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus isolates from blood. In this study, vaginal secretions from HIV-1-infected women were examined for evidence of cellular viral replication that produced virus with properties different from that in blood. Multiply spliced HIV-1 messenger RNA, which is found only in cells replicating virus, was detected in all vaginal lavage samples tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage samples. In addition, significant genotypic differences were found in cell-free virus from matched blood plasma and vaginal secretions. Moreover, drug resistance-associated mutations appeared in plasma virus several months before appearing in vaginal virus. These findings indicate that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood.

Significance of mild cytologic atypia in women infected with human immunodeficiency virus

Objective To determine the prevalence of cervical intraepithelial neoplasia (CIN) in women who are infected with human immunodeficiency virus (HIV) and who have mild cytologic atypia. Methods As part of an ongoing, Prospective study of cervical disease in HIV-infected women, Papanicolaou smears were analyzed cross-sectionally fro the diagnosis of mild cytologic atypia. Results Mild cytologic atypia was diagnosed in 112 (25%) of the 453 HIV-infected women enrolled in this study, compared with 36 (9% of the 401 HIV-uninfected women (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.2–5.1; P < .001). Mild cytologic atypia was diagnosed more frequently in HIV-infected women with lower CD4+T-lymphocyte counts (χ2 for trend, P = .015) and in those with a history of an abnormal Papanicolaou smear or treatment for cervical disease (OR 3.0, 95% CI 1.2–7.6; P = .008). Coexistent CIN was detected by colposcopically directed biopsy in 42 (38%) of the 112 HIV-infected women mild cytologic atypia, compared with five (14%) of the 36 HIV-uninfected women (OR 3.7, 95% CI 1.3–11.9; P = .008). Severe inflammation with associated epithelial reparative atypia was diagnosed in 90 (20%) of the HIV-infected women and in 87 (22%) of the HIV-uninfected women. Coexistent CIN was detected in 12% of HIV-infected women with severe inflammation and associated epithelial reparative atypia, compared with 2% of the HIV-uninfected women with this cytologic diagnosis (OR 5.9, 95% CI 1.2–23; P = .01). Conclusion Mild cytologic atypia, a frequent diagnosis on Papanicolaou smear from HIV-infected women, is associated with CIN. We recommend that all HIV -infected women with mild cytologic atypia be referred for colposcopy.