Jiahong Xu

Persistence of Human Papillomavirus Infection in HIV-Infected and -Uninfected Adolescent Girls: Risk Factors and Differences, by Phylogenetic Type

BACKGROUND High rates of persistence of human papillomavirus (HPV) infection have been reported for adult women with human immunodeficiency virus (HIV) infection. Although most women are first infected with HPV during adolescence, persistence of specific HPV types has not been carefully examined among HIV-infected adolescents. The objective of this study was to examine the rates of and risk factors for persistence of HPV types among HIV-infected and -uninfected adolescent girls. METHODS This is a prospective cohort study of female adolescents, aged 13-18 years, participating in the Reaching for Excellence in Adolescent Care and Health project, a national study of HIV-infected and -uninfected adolescents. The main outcome measured was type-specific loss of initial HPV DNA detected. Loss of HPV DNA was defined for the following categories of HPV DNA types: low risk, which included types 6, 11, 42, 44, 54, 40, 13, 32, 62, 72, 2, 57, and 55; and high risk, which included types 16-like (16, 31, 33, 35, 52, 58, and 67), 18-like (18, 39, 45, 59, 68, 70, 26, 69, and 51), and 56-like (56, 53, and 66). RESULTS Prevalent or incident HPV infection was detected in 334 girls. When type-specific loss of HPV was examined, HIV-uninfected girls had a shorter mean time to loss of initial infection than did HIV-infected girls (403 days vs. 689 days, respectively; P<.0001). By means of multivariate analysis, CD4 immunosuppression and the presence of multiple HPV-type subgroups were found to be associated with persistence of HPV. CONCLUSION Since persistence of high-risk HPV types has been strongly linked with the development of invasive cancer, the prolonged persistence of HPV observed among HIV-infected adolescents who are relatively healthy underscores the importance of prevention of HPV infection in this group.

The Effect of Highly Active Antiretroviral Therapy on Mortality among HIV-Infected Former Plasma Donors in China

BACKGROUND In China, many former plasma donors were infected with the human immunodeficiency virus (HIV) in the early-mid-1990s. Highly active antiretroviral therapy (HAART) was provided for former plasma donors beginning in 2002. The effect of HAART on mortality in this cohort has not been described. METHODS This study is a retrospective analysis of the national HIV epidemiology and treatment databases for the period 1993-2006. All HIV-infected subjects from 10 counties with a high prevalence of HIV infection in 6 provinces were eligible. Inclusion criteria were: (1) history of plasma donation, (2) positive Western blot result, (3) clinical diagnosis of AIDS or CD4(+) cell count <200 cells/microL at any time, and (4) age >or=18 years at AIDS diagnosis. RESULTS Of 9059 eligible subjects, 4093 met the inclusion criteria. Mean age was 41 years, 51% were male, 99% were farmers, and 87% were from Henan Province. Overall mortality decreased from 27.3 deaths per 100 person-years in 2001 to 4.6 deaths per 100 person-years in 2006. Conversely, the percentage of patient-years receiving HAART increased from 0% in 2001 to 70.5% in 2006. In a multivariate Cox proportional hazards analysis, not receiving HAART was the greatest risk factor for mortality (hazard ratio, 2.8; 95% confidence interval, 2.4-3.3). Among treated patients, those who had lower CD4(+) cell counts and higher numbers of opportunistic infections at the initiation of therapy were at greater risk of death. CONCLUSIONS The national treatment program has significantly reduced the mortality rate among HIV-infected former plasma donors through the use of generic drugs in a rural treatment setting with limited laboratory monitoring. Treatment success can be improved through increased coverage and earlier initiation of therapy.

Risk of high-grade squamous intraepithelial lesion in HIV-infected adolescents.

BACKGROUND The risk of developing the human papillomavirus (HPV)-associated precancer high-grade squamous intraepithelial lesion (HSIL) in human immunodeficiency virus (HIV)-infected adolescents is unknown. We examined the risk of developing HSIL among adolescents with and without HIV infection. METHODS HIV-infected (n = 172) and -uninfected (n = 84) girls aged 13-18 years who were participating in a multicenter study of primarily horizontally acquired HIV infections in adolescents (Reaching for Excellence in Adolescent Health Care) and who did not have HSIL on cytologic examination at study entry or at the first follow-up visit were followed at 6-month intervals. HIV-uninfected girls were recruited for comparison in a 2:1 ratio (HIV infected:HIV uninfected). The primary outcome was cytologic diagnosis of HSIL confirmed by expert review. RESULTS Incidence of HSIL by the end of follow-up was higher for HIV-infected girls than for HIV-uninfected girls (21.5% vs. 4.8%, respectively). In multivariate analysis, use of hormonal (either estrogen/progesterone oral combination or medroxyprogesterone acetate intramuscular) contraceptives, high cervical mucous concentrations of interleukin (IL)-12, a positive HPV test, and persistent low-grade squamous intraepithelial lesion (LSIL) were significantly associated with the development of HSIL. CONCLUSIONS The incidence of HSIL was alarmingly high in HIV-infected adolescent girls. However, when other predictors were considered in multivariate analysis, HIV status was not retained in the model. The heightened risk for HSIL associated with persistent LSIL underscores the need to closely monitor HIV-infected adolescents with LSIL. The risk for HSIL associated with high concentrations of IL-12 may be suggestive of a local immune dysregulation. The role of hormonal contraception as a risk factor deserves further investigation.

Immunogenicity and Safety of the Human Papillomavirus 6, 11, 16, 18 Vaccine in HIV-Infected Young Women

BACKGROUND The objective of this study was to determine whether the 3-dose quadrivalent human papillomavirus (HPV) vaccine series (HPV-6, -11, -16, -18) is immunogenic and safe in young women infected with human immunodeficiency virus (HIV). METHODS We enrolled 99 women aged 16-23 years in a phase 2, open-label, multicenter trial, conducted from 2008 to 2011 by the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Outcome measures were immunogenicity 4 weeks after dose 3, measured by (1) geometric mean titers (GMTs) and (2) seroconversion rates for HPV-6, -11, -16, and -18, among those seronegative and HPV DNA negative for each type. Immune responses were compared to those of a historical comparison group of HIV-negative women (n = 267) using univariate methods. Clinical and laboratory adverse events were assessed after each dose. RESULTS The mean age of subjects was 21.4 years; 80% were non-Hispanic black, 69 were not taking antiretroviral therapy (ART), and 30 were taking ART. No differences in GMTs were noted among participants taking ART vs the comparison group, but GMTs were lower in participants not taking ART vs the comparison group for HPV-16 (2393 vs 3892 milli-Merck units per milliliter [mMU/mL], P = .012) and HPV-18 (463 vs 801 mMU/mL, P = .003). Seroconversion rates were 100% for HPV-6, -11, -16, and -18 among participants taking ART. Rates ranged from 92.3% (for HPV-18) to 100.0% (for HPV-6) among participants not taking ART. One severe adverse event (fatigue) was noted. CONCLUSIONS In a sample of HIV-infected women who were HPV DNA and HPV seronegative, immune responses to HPV vaccination were generally robust and the vaccine was well tolerated.

Hiv-inducing factor in cervicovaginal secretions is associated with bacterial vaginosis in HIV-1-infected women

Objective:Certain cervicovaginal lavage (CVL) fluid samples obtained from HIV-1-infected and uninfected women stimulate in vitro HIV-1 replication. This activity, HIV-inducing factor (HIF), changes when CVL fluid is heated. We sought to confirm a previous observation that HIF was associated with bacterial vaginosis (BV). Methods:HIF was measured in unheated and heated CVL fluid obtained from HIV-1-infected women and compared with the presence of BV by Nugent scores, other genital tract conditions, and cervicovaginal HIV-1 shedding. Results:Among the 295 women studied, 54% of CVL samples had HIF activity and 21% showed heat-stable HIF activity. In adjusted logistic regression, heat-stable HIF was associated with BV (odds ratio [OR] = 51.7, 95% confidence interval [CI]: 5.0, 530.7) and with intermediate flora (OR = 43.3, 95% CI: 3.6, 521.1); heat-labile HIF was not associated with BV. Neither heat-stable nor heat-labile HIF was associated with other cervicovaginal conditions nor, after controlling for plasma viral load, with genital tract HIV-1 shedding. Conclusion:We confirmed the association of HIF with BV and attribute it to the heat-stable component. Heat-stable activity is also associated, although less strongly, with intermediate vaginal flora. We propose that heat-stable HIF is a result of products of BV-associated bacteria.

HIV type 1 and cytomegalovirus coinfection in the female genital tract

The relationship between human immunodeficiency virus (HIV) type 1 and human cytomegalovirus (CMV) was studied in blood, saliva, and cervicovaginal lavage (CVL) specimens from 33 HIV-1-infected women. An association between HIV-1 RNA and CMV DNA was found in the CVL specimens, which also were tested for cytokine levels. Women with detectable CMV DNA in CVL specimens were more likely to have higher interleukin (IL)-1 beta and IL-8 levels than were women with undetectable CMV DNA in CVL specimens. More than 1 strain of CMV was detected in specimens from 2 patients. These results suggest mechanisms by which CMV coinfection could affect HIV-1 disease progression.

Gender Difference in 2-Year Mortality and Immunological Response to ART in an HIV-Infected Chinese Population, 2006–2008

Background Since it was initiated in 2002, the China Free Antiretroviral Treatment (ART) Program has been progressing from an emergency response to a standardized treatment and care system. As of December 31, 2009, a total of 81,880 patients in 31 provinces, autonomous regions, and special municipalities received free ART. Gender differences, however, in mortality and immunological response to ART in this cohort have never been described. Objective To understand whether women and men who enrolled in the China National Free ART Program responded equally well to the treatment. Methods A retrospective analysis of the national free ART databases from June 2006–December 2008 was performed. HIV-infected subjects who were 18 years or older, ART naïve at baseline, and on a 3TC regimen enrolled in the program from June 1 to December 31, 2006, were included in this study, then followed up to 2 years. Results Among 3457 enrolled subjects who met the inclusion criteria, 59.2% were male and 40.8% female. The majority of the subjects were 19–44 years old (77%) and married (72%). Over the full 24 months of follow-up, the mortality rate was 19.0% in males and 11.4% in females (p = 0.0014). Males on therapy for 3–24 months were more likely to die than females (HR = 1.46, 95% CI: 1.04–2.06, p = 0.0307) after adjusting for baseline characteristics. Compared to men, women had higher CD4+ counts over time after initiating ART (p<0.0001). Conclusions Our study showed that women had an overall lower mortality and higher CD4+ counts than men in response to ART treatment, which may be attributed to adherence, biological factors, social, cultural and economic reasons. Further study is needed to explore these factors that might contribute to the gender differences in mortality and immunological response to ART.

Improving comprehension for HIV vaccine trial information among adolescents at risk of HIV.

Abstract A simplified version of the HIVNET prototype HIV vaccine process was developed for adolescents at risk of HIV by: (1) reducing reading level; (2) reorganizing; (3) adding illustrations; and (4) obtaining focus group feedback. Then adolescents (N = 187) in three cities were randomly assigned to the standard or simplified version. Adolescents receiving the simplified version had significantly higher comprehension scores (80% correct vs. 72% correct), with 37% of items significantly more likely to be answered correctly. They were also significantly more likely to recall study benefits and procedures. Overall, adolescents were less willing to participate in a potential HIV vaccine trial after presentation than prior to presentation. The present study indicates that it would be feasible for adolescents to participate in a vaccine trial, as simplification of vaccine information, combined with illustrations to depict key concepts, resulted in improved scores for adolescents on the comprehension and recall test.

Chlamydia and Gonorrhea in HIV-Infected Pregnant Women and Infant HIV Transmission.

Background Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. The prevalence of STIs and its association with HIV mother-to-child transmission (MTCT) were evaluated in a substudy analysis from a randomized, multicenter clinical trial. Methodology Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction testing for the detection of CT and NG (Xpert CT/NG; Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA polymerase chain reaction at 3 months. Results Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission), the lowest transmission rate occurred among infants born to CT- and NG-uninfected mothers (8.1%) as compared with those infected with only CT (10.7%) and both CT and NG (14.3%; P = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (odds ratio, 1.47; 95% confidence interval, 0.9–2.3; P = 0.09). Conclusions This cohort of HIV-infected pregnant women is at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high-risk cohort of HIV-infected women.

Risk Perceptions After Human Papillomavirus Vaccination in HIV-Infected Adolescents and Young Adult Women

PURPOSE To examine risk perceptions (perceived risk of human papillomavirus [HPV], perceived risk of other sexually transmitted infections [STIs], and need for safer sexual behaviors) and to determine factors associated with these risk perceptions after HPV vaccination. METHODS Data were collected at the baseline visit of an HPV-6, -11, -16, -18 vaccine clinical trial in 16-23-year-old HIV-infected young women (N = 99). Immediately after receiving the first vaccine dose, participants completed a confidential questionnaire that included three 5-item scales measuring perceived risk of HPV, perceived risk of other STIs, and need for safer sexual behaviors. Linear and logistic regression models were used to examine associations between baseline characteristics (demographic characteristics; cluster of differentiation antigen 4 (CD4(+)) count; HIV viral load; knowledge about HPV and HPV vaccines; sexual behaviors; and STI diagnosis) and each measure of risk perceptions. RESULTS Most participants perceived themselves to be at lower risk for HPV (mean scale score = 19.5/50), most perceived that they were not at lower risk for other STIs (mean = 31.2/50), and the vast majority reported that there was still a need for safer sexual behaviors after vaccination (mean = 43.1/50). Multivariate analyses indicated that knowledge about HPV and HPV vaccines was associated with perceived need for safer sexual behaviors (OR = 1.05, 95% CI = 1.0-1.1). CONCLUSIONS Although almost all young women in this study believed that safer sexual behaviors were still important after HPV vaccination, a subset believed they were at less risk for STIs other than HPV. Educational interventions are needed to prevent misperceptions and promote healthy behaviors after vaccination.