Nancy A. Hessol

Long-term HIV-1 infection without immunologic progression.

Objective:To identify and describe a subgroup of men infected with HIV for 10–15 years without immunologic progression, and to evaluate the effect of sexually transmitted diseases (STD) and recreational drug use on delayed HIV disease progression. Design: Inception cohort study. Setting: Municipal STD clinic. Participants:A total of 588 men with well documented dates of HIV seroconversion and 197 HIV-seronegative controls. Main outcome measures:AIDS, CD4+ count, rate of CD4+ cell loss, CD8+ count, β2-microglobulin, complete blood count, p24 antigen and HIV-related symptoms. Results:Of 588 men, 69% had developed AIDS by 14 years after HIV seroconversion (95% confidence interval, 64–73%). Of 539 men with HIV seroconversion dates prior to 1983, 42 men (8%) were healthy long-term HIV-positives (HLP), HIV-infected > 10 years without AIDS and with CD4+ counts >500 × 106/l. When compared with progressors (men with HIV seroconversion prior to 1983 but with AIDS or CD4+ counts <200 × 106/l, HLP had a significantly slower rate of CD4+ decline (6 versus 85x106/l cells/year), and less abnormal immunologic, hematologic and clinical parameters. However, when compared with HIV-uninfected controls, HLP demonstrated lower CD4+ counts and mild hematologic abnormalities. There were no consistent differences between HLP and progressors in prior exposure to recreational drugs or STD. Conclusion:There are individuals with long-term HIV infection who appear clinically and immunologically healthy 10–15 years after HIV seroconversion, with stable CD4+ counts. Lack of exposure to STD or recreational drugs does not appear to explain the delayed course of disease progression in HLP.

The Women's Interagency HIV Study: an Observational Cohort Brings Clinical Sciences to the Bench

The Womens 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 HIV-related 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.

Depressive Symptoms and AIDS-Related Mortality Among a Multisite Cohort of HIV-Positive Women

OBJECTIVES We examined associations between depressive symptoms and AIDS-related mortality after controlling for antiretroviral therapy use, mental health treatment, medication adherence, substance abuse, clinical indicators, and demographic factors. METHODS One thousand seven hundred sixteen HIV-seropositive women completed semiannual visits from 1994 through 2001 to clinics at 6 sites. Multivariate Cox and logistic regression analyses estimated time to AIDS-related death and depressive symptom severity. RESULTS After we controlled for all other factors, AIDS-related deaths were more likely among women with chronic depressive symptoms, and symptoms were more severe among women in the terminal phase of their illness. Mental health service use was associated with reduced mortality. CONCLUSIONS Treatment for depression is a critically important component of comprehensive care for HIV-seropositive women, especially those with end-stage disease.

Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America

BACKGROUND Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. METHODS In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). RESULTS Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7-151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8-6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5-2.2). In comparison with the period 2000-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3-.9) in 1996-1999 and 0.9 (95% CI, .6-1.2) in 2004-2007. CONCLUSIONS Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.

The prevalence of oral lesions in HIV-infected homosexual and bisexual men : three San Francisco epidemiological cohorts

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposis sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CD 17.5–23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% Cl 4.1–7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposis sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P < 0.05). The prevalence of erythematous candidiasis and Kaposis sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Course of HIV-I infection in a cohort of homosexual and bisexual men: An 11 year follow up study

OBJECTIVE--To characterise the natural history of sexually transmitted HIV-I infection in homosexual and bisexual men. DESIGN--Cohort study. SETTING--San Francisco municipal sexually transmitted disease clinic. PATIENTS--Cohort included 6705 homosexual and bisexual men originally recruited from 1978 to 1980 for studies of sexually transmitted hepatitis B. This analysis is of 489 cohort members who were either HIV-I seropositive on entry into the cohort (n = 312) or seroconverted during the study period and had less than or equal to 24 months between the dates of their last seronegative and first seropositive specimens (n = 177). A subset of 442 of these men was examined in 1988 or 1989 or had been reported to have developed AIDS. MAIN OUTCOME MEASURES--Development of clinical signs and symptoms of HIV-I infection, including AIDS, AIDS related complex, asymptomatic generalised lymphadenopathy, and no signs or symptoms of infection. MEASUREMENTS AND MAIN RESULTS--Of the 422 men examined in 1988 or 1989 or reported as having AIDS, 341 had been infected from 1977 to 1980; 49% (167) of these men had died of AIDS, 10% (34) were alive with AIDS, 19% (65) had AIDS related complex, 3% (10) had asymptomatic generalised lymphadenopathy, and 19% (34) had no clinical signs or symptoms of HIV-I infection. Cumulative risk of AIDS by duration of HIV-I infection was analysed for all 489 men by the Kaplan-Meier method. Of these 489 men, 226 (46%) had been diagnosed as having AIDS. We estimated that 13% of cohort members will have developed AIDS within five years of seroconversion, 51% within 10 years, and 54% within 11.1 years. CONCLUSION--Our analysis confirming the importance of duration of infection to clinical state and the high risk of AIDS after infection underscores the importance of continuing efforts both to prevent transmission of HIV-I and to develop further treatments to slow or stall the progression of HIV-I infection to AIDS.

Increased Incidence of Hodgkin Disease in Homosexual Men with HIV Infection

OBJECTIVE To evaluate the incidence of Hodgkin disease and non-Hodgkin lymphoma among homosexual men infected with human immunodeficiency virus (HIV). DESIGN Cohort study with computer-matched identification of participants with the Northern California Cancer Center registry. Population rate comparisons were made with data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry. PARTICIPANTS The 6704 homosexual men in the San Francisco City Clinic Cohort study. MEASUREMENTS Incidence of Hodgkin disease, non-Hodgkin lymphoma, HIV infection, and the acquired immunodeficiency syndrome (AIDS); calculation of sex and age-adjusted standardized morbidity ratios and attributable risk. RESULTS Eight cases of Hodgkin disease and 90 cases of non-Hodgkin lymphoma were identified through computer matching among cohort members residing in the San Francisco Bay area from 1978 through 1989. Among the HIV-infected men, the age-adjusted standardized morbidity ratio was 5.0 (95% CI, 2.0 to 10.3) for Hodgkin disease and 37.7 (CI, 30.3 to 46.7) for non-Hodgkin lymphoma. The excess risk attributable to HIV infection was 19.3 cases of Hodgkin disease per 100,000 person-years and 224.9 cases of non-Hodgkin lymphoma per 100,000 person-years. CONCLUSION An excess incidence of Hodgkin disease was found in HIV-infected homosexual men. Additional well-designed epidemiologic studies are needed to determine whether Hodgkin disease should be considered an HIV-related malignancy.

Causes of death among women with human immunodeficiency virus infection in the era of combination antiretroviral therapy

PURPOSE To examine changes in the causes of death and mortality in women with human immunodeficiency virus (HIV) infection in the era of combination antiretroviral therapy. METHODS Among women with, or at risk of, HIV infection, who were enrolled in a national study from 1994 to 1995, we used an algorithm that classified cause of death as due to acquired immunodeficiency syndrome (AIDS) or non-AIDS causes based on data from death certificates and the CD4 count. Poisson regression models were used to estimate death rates and to determine the risk factors for AIDS and non-AIDS deaths. RESULTS Of 2059 HIV-infected women and 569 who were at risk of HIV infection, 468 (18%) had died by April 2000 (451 HIV-infected and 17 not infected). Causes of death were available for 428 participants (414 HIV-infected and 14 not infected). Among HIV-infected women, deaths were classified as AIDS (n = 294), non-AIDS (n = 91), or indeterminate (n = 29). The non-AIDS causes included liver failure (n = 19), drug overdose (n = 16), non-AIDS malignancies (n = 12), cardiac disease (n = 10), and murder, suicide, or accident (n = 10). All-cause mortality declined an average of 26% per year (P = 0.03) and AIDS-related mortality declined by 39% per year (P = 0.01), whereas non-AIDS-related mortality remained stable (10% average annual decrease, P = 0.73). Factors that were independently associated with non-AIDS-related mortality included depression, history of injection drug use with hepatitis C infection, cigarette smoking, and age. CONCLUSION A substantial minority (20%) of deaths among women with HIV was due to causes other than AIDS. Our data suggest that to decrease mortality further among HIV-infected women, attention must be paid to treatable conditions, such as hepatitis C, depression, and drug and tobacco use.

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

ObjectiveThis study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DesignCohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions.Setting: We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. ParticipantsOf the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. Main outcome measuresWe determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. ResultsUsing proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CD, 1.2–2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1–17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6–6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. ConclusionThe presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Anal intraepithelial neoplasia in a multisite study of HIV-infected and high-risk HIV-uninfected women.

Objectives:To study anal intraepithelial neoplasia and its associations with anal and cervical human papillomavirus (HPV), cervical neoplasia, host immune status, and demographic and behavioral risk factors in women with and at risk for HIV infection. Design:Point-prevalence analysis nested within a prospective study of women seen at three clinical centers of the Womens Interagency HIV Study. Methods:In 2001–2003 participants were interviewed, received a gynecological examination, anal and cervical cytology testing and, if abnormal, colposcopy-guided or anoscopy-guided biopsy of visible lesions. Exfoliated cervical and anal specimens were assessed for HPV using PCR and type-specific HPV probing. Logistic regression analyses were performed, and odds ratios (ORs) estimated risks for anal intraepithelial neoplasia. Results:Four hundred and seventy HIV-infected and 185 HIV-uninfected women were enrolled. Low-grade anal intraepithelial neoplasia was present in 12% of HIV-infected and 5% of HIV-uninfected women. High-grade anal intraepithelial neoplasia was present in 9% of HIV-infected and 1% of HIV-uninfected women. In adjusted analyses among HIV-infected women, the risk factors for low-grade anal intraepithelial neoplasia were younger age [OR = 0.59, 95% confidence interval (CI) = 0.36–0.97], history of receptive anal intercourse (OR = 3.2, 95% CI = 1.5–6.8), anal HPV (oncogenic types only OR = 11, 95% CI = 1.2–103; oncogenic and nononcogenic types OR = 11, 95% CI = 1.3–96), and cervical HPV (oncogenic and nononcogenic types OR = 3.5, 95% CI = 1.1–11). In multivariable analyses among HIV-infected women, the only significant risk factor for high-grade anal intraepithelial neoplasia was anal HPV infection (oncogenic and nononcogenic types OR = 7.6, 95% CI = 1.5–38). Conclusion:Even in the era of highly active antiviral therapy, the prevalence of anal intraepithelial neoplasia was 16% in HIV-infected women. After controlling for potential confounders, several risk factors for low-grade anal intraepithelial neoplasia differed from risk factors for high-grade anal intraepithelial neoplasia.