Association of vitamin A deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women

To explore the relationship between vitamin A (retinol) deficiency and cervical squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women, we measured serum retinol concentrations in 1314 women enrolled in the Women's Interagency HIV Study and correlated the results with concurrent cervical cytology. At the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (<1.05 micromol/L). Analysis of Papanicolaou smears showed SILs in 216 (16.4%) of 1314 women. Cervical SILs were found to be associated with retinol concentrations <1.05 micromol/L (multivariate odds ratio [OR], 1.63; P=.04) in a multivariate model, which included human papillomavirus (HPV) status and markers of nutritional status and HIV disease stage. In the subset of women with genital HPV (n=774), a multivariate analysis again revealed a significant independent association between retinol <1.05 micromol/L and cervical SILs (multivariate OR, 1.75; P=.02). Our findings suggest that retinol deficiency may contribute to the development of cervical SILs in HIV-infected women.     

Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women

We examined incidence and correlates of progression and regression of abnormal cervical cytologic test results, defined as at least low-grade squamous intraepithelial lesions (SILs), in 774 human immunodeficiency virus (HIV)-seropositive and 391 HIV-seronegative women monitored semiannually for up to 5.5 years. During follow-up, 224 (35%) HIV-seropositive women and 34 (9%) HIV-seronegative women had incident SILs detected by Pap test; 47 (7%) HIV-seropositive women developed high-grade lesions. The incidence of SILs was 11.5 cases among HIV-seropositive and 2.6 cases among HIV-seronegative women per 100 person-years of observation (rate ratio, 4.5; 95% confidence interval, 3.1-6.4; P<.001). Risk of incident SILs and likelihood of Pap test progression were increased among HIV-seropositive women with CD4(+) lymphocyte counts <500 cells/mm(3) and among women with human papillomavirus (HPV) infection, with risk-ordering from low- to high-risk HPV type. SIL regression was less likely among HIV-seropositive women with higher HIV loads. No beneficial effect of highly active antiretroviral therapy was demonstrated.     

Genotypes and sequence variants of human papillomavirus DNAs from human immunodeficiency virus type 1-infected women with cervical intraepithelial neoplasia.

Human papillomavirus (HPV) DNA was found in cervicovaginal lavage fluids from 9 of 11 human immunodeficiency virus type 1 (HIV-1)-seropositive female prostitutes with cervical intraepithelial neoplasia (CIN) in Kinshasa, Zaire. Since 7 yielded complex nucleic acid hybridization results consistent with mixed HPV infections, limited sequencing of HPV DNA was used to identify the HPVs present. Three of HPV 16 and 1 each of HPV 18, 31, 33, and 56 and ME180-HPV were identified by sequencing in 8 samples. Each of these genotypes has been found in specimens from HIV-1-seronegative women with CIN. Some DNAs had nucleic acid and amino acid sequence variations relative to the reference HPVs, but the variants were closely related to variants that have been found in HIV-1-seronegative women. Variant amino acids were found predominantly at three positions in one 40-amino-acid segment of the L1 open reading frame sequenced. The predominant HPV 16 variant observed has been found rarely in other countries.     

High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients

OBJECTIVE: To determine rates of human papillomavirus (HPV) infections, abnormal cervical smears, and squamous intraepithelial lesions (SIL) among women with systemic lupus erythematosus (SLE). METHODS: We investigated 30 women with SLE, 67 with abnormal smears from colposcopy clinics, and 15 community subjects with normal smears. Polymerase chain reaction results for viral DNA and HPV-16 sequencing data were correlated to cytology and colposcopic findings. RESULTS: SLE and colposcopy patients were more likely (P < 0.05) to be HPV positive (15 [54%] and 37 [67%] patients, respectively) and HPV-16 DNA positive (16 [57%] and 17 [31%] patients, respectively) than community subjects (0% HPV DNA positive and 1 [6%] HPV-16 DNA positive). SLE patients were also more likely to be HPV-16 DNA positive than colposcopy patients (P < 0.05). SLE patients with a high HPV-16 viral load more frequently had SIL (n = 6) than those with a low HPV-16 viral load (n = 1; P < 0.05). HPV and HPV-16 DNA positivity were not associated with previous or current drug therapy for SLE patients. All HPV-16 DNA sequences from 6 SLE and 5 colposcopy patients were the European-type variant. Eighteen (60%) SLE patients had a previous or current cervical abnormality. At the time of study, 5 (17%) SLE patients had an abnormal cervical smear and 8 (27%) had SIL. For those diagnosed with SLE for >10 years, the rate of SIL was 44% lower than those with SLE for <5 years (odds ratio 0.56, 95% confidence interval 0.1-3.5). CONCLUSION: UK women with a recent SLE diagnosis had disturbingly elevated levels of HPV infections (particularly with European HPV-16 variants at a high viral load), abnormal cervical cytology, and SIL.     

Self-reported bacterial infections among women with or at risk for human immunodeficiency virus infection.

Bacterial infections are a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV) infection, particularly women. We performed a cross-sectional analysis of a history of bacterial infections among 1,310 women with or at risk for HIV infection. HIV-seropositive women were significantly more likely than seronegative women to report recent and lifetime histories of bacterial infection, even after history of injection drug use since 1977 was adjusted for; this included recent pneumonia (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.5-6.6), sinusitis (OR, 1.4; 95% CI, 1.0-2.0), and urinary tract infection (OR, 1.5; 95% CI, 1.1-2.1). Compared with HIV-negative women, women with CD4 cell counts of <200 were about eight times more likely to report recent pneumonia (OR, 7.8; 95% CI, 3.4-17.7); those with CD4 cell counts of 200-500 were almost three times more likely to do so (OR, 2.6; CI, 1.2-5.7). Logistic regression analysis revealed that only CD4 cell category and a recent history of smoking had a significant relationship to self-reported pneumonia.     

Insulin-like growth factor system gene expression in cervical scrapes from women with squamous intraepithelial lesions and cervical cancer

BACKGROUND: There is ample evidence that the insulin-like growth factors (IGF) system is involved in the development of several types of cancer. The aim of this study was to evaluate the expression levels of IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and IGF-I receptor (IGF-IR) in exfoliated cervical cells in cervical carcinogenesis. METHODS: mRNA levels of IGF-I, IGF-II, IGFBP-3 and IGF-IR were assessed by real-time PCR in 105 cervical scrapes obtained from 16 patients diagnosed with low-grade squamous intraepithelial lesions (LSIL), 24 with high-grade SIL (HSIL), 23 with cervical cancer, and 42 from controls with normal Papanicolau (Pap) test. RESULTS: IGF-I mRNA levels were very low and no significant differences were seen between control and other groups. IGF-II mRNA levels were significantly lower in LSIL than in control group (median [arbitrary units]: 0.38 vs. 2.42, P=0.006) but its expression in HSIL and cervical cancer was similar to the one observed in controls. IGFBP-3 mRNA levels were significantly lower in cancer than in controls (median [arbitrary units]: 0.43 vs. 0.73, P=0.03). We observed a decrease in IGF-IR gene expression as the SIL degree increased (median for controls, LSIL, HSIL, and cervical carcinoma [arbitrary units]: 31.24, 9.08, 8.95, and 3.56, respectively). IGF-IR mRNA levels were significantly lower in HSIL and cervical cancer in comparison with controls (P=0.043 and P<0.001, respectively). CONCLUSIONS: The present observations suggest that a reduced expression of IGFBP-3 and IGF-IR can be associated with progression to cervical cancer; the specific role played by the IGF-IR in this process remains unclear.     

Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women: opportunities for intervention

Sexually transmitted diseases (STDs) are cofactors for human immunodeficiency virus (HIV) transmission, but the specific role of herpes simplex virus type 2 (HSV-2) is unclear. This study aimed to examine the in vivo relationships between HSV-2 and HIV-1 in 300 women in Bangui, Central African Republic. Sera were tested for syphilis, HIV-1, HSV-2 antibody, and levels of vitamins A and E. Genital specimens were tested for other STDs. HSV-2 DNA and HIV-1 RNA were quantified in cervicovaginal lavage. The prevalences of HSV-2 antibody (91% vs. 78%, P=.02), HSV-2 shedding (43% vs. 22%, P=. 003), and levels of HSV-2 DNA (P=.01) were all significantly higher among HIV-1-seropositive than among HIV-1-seronegative women. There was a significant correlation between genital HIV-1 RNA and HSV-2 DNA levels (P=.02) among the 23 women who were shedding HSV-2 DNA. If confirmed, such associations highlight the urgent need for HSV-2 control measures in populations at high risk of both infections.     

Short-term follow up of cervical squamous intraepithelial lesions associated with HIV and human papillomavirus infections in Africa.

A prospective study in gynaecology clinics was conducted in Abidjan, C?te d'Ivoire, to assess the short-term evolution of squamous intraepithelial lesions (SILs). Of 94 women with a cytological diagnosis of SIL, 38 were infected with HIV. The average follow-up period after the initial smear was 5 months. Detection of human papillomavirus (HPV) by polymerase chain reaction (PCR) was performed at both the time of enrolment and final follow-up smear. There were 39 cases of persistent SILs. HIV-positive women had a higher percentage of persistent SIL (76%) than HIV-negative women (18%, relative risk (RR)=4.3, 95% confidence interval (CI) = 2.4, 7.7). SILs were more frequent among women infected with HPV at the time of enrolment or with persistent HPV infection, but these associations disappeared after adjusting for HIV serostatus. Spontaneous regression of SILs commonly occurs in HIV-negative African women. HIV-infected women with cervical dyskaryosis require gynaecology follow-up.     

Cervical cytological abnormalities and factors associated with high-grade squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro, Brazil

Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11-6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11-0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.     

Prevalence and predictors of intestinal helminth infections among human immunodeficiency virus type 1-infected adults in an urban African setting

Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1-infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data from 297 HIV-1-infected adults (mean age = 31.1 years, 69% female) living in Lusaka, Zambia to assess the prevalence and associated predictors of helminth infection. We found at least one type of intestinal helminth in 24.9% of HIV-infected adults. Thirty-nine (52.7%) were infected with Ascaris lumbricoides, and 29 (39.2%) were infected with hookworm. More than 80% were light-intensity infections. A recent visit to a rural area, food shortage, and prior history of helminth infection were significant predictors of current helminth status. The high helminth prevalence and potential for adverse interactions between helminths and HIV suggests that helminth diagnosis and treatment should be part of routine HIV care.     

Human papillomavirus type 33 polymorphisms and high-grade squamous intraepithelial lesions of the uterine cervix

BACKGROUND: We investigated the association between polymorphisms of human papillomavirus (HPV)-33 and squamous intraepithelial lesions (SILs). METHODS: Endocervical specimens from 89 women infected with HPV-33, out of a total of 5347 recruited for 2 case-control and 2 cohort studies, were further analyzed by polymerase chain reaction sequencing of the long control region (LCR), E6, and E7. RESULTS: Of the 89 samples, 64 were normal, 7 had low-grade SILs (including 3 determined by histopathologic analysis), 15 had high-grade SILs (HSILs, including 14 determined by histopathologic analysis), and 3 had an unknown diagnosis. Non-prototype-like LCR variants were significantly associated with HSILs (age- and study site-adjusted odds ratio [OR], 9.2 [95% confidence interval {CI}, 1.8-45.9]). The C7732G variation, which results in the loss of a putative binding site for the cellular upstream stimulatory factor, was associated with HSILs (age- and site-adjusted OR, 8.0 [95% CI, 1.5-42.8]). E6 and E7 polymorphisms were not associated with HSILs. Samples collected at 6-month intervals from 14 participants contained the same variant. The HPV-33 MT 1-0-0 variant carrying the G7584A variation was detected more frequently in women from Brazil (7/20 [35%]) than in women from Canada (1/65 [1.5%]; P=.001). CONCLUSION: Intratypic LCR variants of HPV-33 seem to vary geographically and to differ with respect to their oncogenic potential.     

Association of herpes simplex virus type 2 with the human immunodeficiency virus among urban women in Zimbabwe

A cross-sectional study at two urban primary health care clinics in Zimbabwe was conducted among 393 consecutive women. The purpose was to determine the seroprevalence of herpes simplex virus type 2 (HSV-2), to identify coinfections and to determine the association between HSV-2, HIV and other sexually transmitted infections (STIs). Sera were tested for HSV-2, HIV and syphilis. Genital specimens were tested for the other STIs. The seroprevalence of ulcerative STIs tested was 42.2% for HSV-2 and 3.9% for syphilis. HSV-2 seropositive women had twice the risk of being HIV infected compared to HSV-2 seronegative women, adjusted OR=2.05 (95% CI=1.29-3.23). HSV-2 seropositivity was also associated with older age, a lower level of education, increase in the number of lifetime sexual partners and history of genital ulcers in the past six or more months. Our data suggest that in this population HSV-2 may contribute more to HIV infection than syphilis because of its high frequency. There is an urgent need for development of an effective HSV-2 vaccine.     

Antibody-dependent cell-mediated cytotoxicity in cervical lavage fluids of human immunodeficiency virus type 1--infected women

Studies were designed to determine whether cervical antibodies in human immunodeficiency virus type 1 (HIV-1)-infected women participate in antibody-dependent cell-mediated cytotoxicity (ADCC). Serum and cervical lavage fluid (CVL) ADCC titers were compared with plasma virus load and CD4 cell number in 45 infected and 10 uninfected women from the Women's Interagency HIV Study. Serum and CVL were incubated with normal peripheral blood lymphocytes and HIV-1 gp120-bearing target cells in a standard (51)Cr-release assay. When stringent criteria were used to define ADCC activity, 63% had activity in > or = 1 fluid sample, 56% had serum titers, and 16% had CVL titers. Serum titers did not predict CVL titers. Three women with CVL ADCC had no serum ADCC, which suggests that ADCC antibodies may be produced locally. ADCC antibodies are present in the cervicovaginal fluids, which indicates that this form of innate immunity can contribute to mucosal defense against HIV-1.     

Increased risk of early measles in infants of human immunodeficiency virus type 1-seropositive mothers.

An increase in illness due to measles is one of the potential consequences of the human immunodeficiency virus (HIV) epidemic in Africa. During a study of perinatal HIV transmission conducted in Kenya, the risk of acquiring measles before vaccination (9 months of age) was found to be 3.8 times higher in infants born to HIV-seropositive mothers than in control infants (10 [9%] of 109 vs. 5 [3%] of 194 infants; P = .02; odds ratio, 3.8; 95% confidence interval, 1.2-13.2). The majority of infants who developed measles in this study had significant sequelae related to their measles infection. The increased risk of measles appeared to be related to relatively lower anti-measles antibody titers detected in cord blood samples of affected infants born to HIV-seropositive mothers. However, 94% of all infants were susceptible to measles on the basis of ELISA testing at age 6 months regardless of maternal HIV serology. These observations highlight the need for improved measles vaccination strategies in Africa and for studies to delineate the effects of HIV infection on the incidence, presentation, and sequelae of childhood infectious illnesses.     

Virus levels in untreated African infants infected with human immunodeficiency virus type 1

In developed areas, human immunodeficiency virus (HIV)-infected infants have high virus levels and rapidly progress to death. HIV levels were assessed in 1994-1997 in untreated infants in Malawi by analysis of dried blood spots tested by nucleic acid silica-bound amplification. Of 24 umbilical cord blood (CB)-positive samples, 83% had >10,000 copies/mL. The median virus level was 78,000 copies/mL. First positive sample median levels were 355,000 copies/mL among 52 perinatally infected infants and 130,000 copies/mL among 43 infants infected by breast-feeding. Virus levels were stable, and initial levels predicted levels 1 year after infection (P=.005), at which time levels did not significantly differ among in utero, perinatally, or postnatally infected infants. Thus, neither age at infection nor route of infection significantly influenced HIV levels measured 1 year after infection. Most (87%) CB-positive infants were infected before labor onset, since virus levels greatly exceeded those expected in their mothers.     

Prevalence and risk factors for cervical intraepithelial neoplasia among HIV-infected women

ObjectivesTo evaluate the prevalence and the risk factors for cervical intraepithelial neoplasia (CIN) among HIV-infected women.MethodsCross-sectional study of 494 HIV-infected women in Brazil, between 1998 and 2008. Gynecologic exam was performed, and samples were collected for cervical cytology and for HPV DNA detection. Cervical biopsy was carried out when indicated. HPV infection, CD4 T-lymphocyte count and HIV viral load were compared with cervical histopathology. Univariate and multivariate statistical analyses were performed to evaluate the statistical association of several risk factors.ResultsCIN prevalence detected by histopathology was 23.4% (6% of CIN2/3 and 17.4% cases of CIN1). Multivariate analysis confirmed an independent association of CIN with CD4 T-lymphocyte count below 200 cells/mm³ (OR 5.0, 95% CI 2.5–10.1), with a positive detection of HPV DNA (OR 2.0, 95% CI 1.2–3.5), and with age ≤ 34 years old (OR 1.5, 95% CI 1.0–2.4). HIV viral load and antiretroviral use were not independent risk factors for CIN.ConclusionsSeverity of immunosupression, presence of HPV infection and younger age are strong predictors of CIN among HIV-infected women.     

Increased hepatitis C virus load among injection drug users infected with human immunodeficiency virus and human T lymphotropic virus type II

Coinfection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and/or human T-lymphotropic virus type II (HTLV-II) is common among drug users. We compared HCV RNA detection and load in a cohort of 6570 injection drug users from 9 US cities during 1987-1991. Of 385 subjects selected from 16 strata by sex, race (black or nonblack), and HIV/HTLV-II group (HIV positive [HIV(+)]/HTLV-II(+), HIV(+)/HTLV-II negative [HTLV-II(-)], HIV(-)/HTLV-II(+), and HIV(-)/HTLV-II(-)), 376 had HCV antibodies, of whom 305 had detectable HCV load. HCV RNA detection was unrelated to sex, race, and virus groups, but differed by study site. The mean HCV load was 5.4 log(10) IU/mL and was 0.24 log(10) higher in men than in women. Virus load increment with HIV or HTLV-II infection was higher among white subjects than among other subjects. Compared with HIV(-)/HTLV-II(-) subjects, virus load was 0.50, 0.22, and 0.56 log(10) higher in HIV(+)/HTLV-II(-), HIV(-)/HTLV-II(+), and HIV(+)/HTLV-II(+) subjects, respectively. HTLV-II infection significantly increased HCV load in white subjects but not in other racial groups.     

Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease

CONTEXT: Metabolic changes and smoking are common among HIV patients and may confer increased cardiovascular risk. OBJECTIVE: The aim of the study was to determine acute myocardial infarction (AMI) rates and cardiovascular risk factors in HIV compared with non-HIV patients in two tertiary care hospitals. DESIGN, SETTING, AND PARTICIPANTS: We conducted a health care system-based cohort study using a large data registry with 3,851 HIV and 1,044,589 non-HIV patients. AMI rates were determined among patients receiving longitudinal care between October 1, 1996, and June 30, 2004. MAIN OUTCOME MEASURES: The primary outcome was myocardial infarction, identified by International Classification of Diseases coding criteria. RESULTS: AMI was identified in 189 HIV and 26,142 non-HIV patients. AMI rates per 1000 person-years were increased in HIV vs. non-HIV patients [11.13 (95% confidence interval [CI] 9.58-12.68) vs. 6.98 (95% CI 6.89-7.06)]. The HIV cohort had significantly higher proportions of hypertension (21.2 vs. 15.9%), diabetes (11.5 vs. 6.6%), and dyslipidemia (23.3 vs. 17.6%) than the non-HIV cohort (P < 0.0001 for each comparison). The difference in AMI rates between HIV and non-HIV patients was significant, with a relative risk (RR) of 1.75 (95% CI 1.51-2.02; P < 0.0001), adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. In gender-stratified models, the unadjusted AMI rates per 1000 person-years were higher for HIV patients among women (12.71 vs. 4.88 for HIV compared with non-HIV women), but not among men (10.48 vs. 11.44 for HIV compared with non-HIV men). The RRs (for HIV vs. non-HIV) were 2.98 (95% CI 2.33-3.75; P < 0.0001) for women and 1.40 (95% CI 1.16-1.67; P = 0.0003) for men, adjusting for age, gender, race, hypertension, diabetes, and dyslipidemia. A limitation of this database is that it contains incomplete data on smoking. Smoking could not be included in the overall regression model, and some of the increased risk may be accounted for by differences in smoking rates. CONCLUSIONS: AMI rates and cardiovascular risk factors were increased in HIV compared with non-HIV patients, particularly among women. Cardiac risk modification strategies are important for the long-term care of HIV patients.     

Hormonal contraception and risk of cervical infections among HIV-1-seropositive Kenyan women

OBJECTIVE: To evaluate the relationship between hormonal contraceptive use and the acquisition of cervical sexually transmitted infections (STI) among HIV-1-infected women. DESIGN: A prospective cohort study of 242 commercial sex workers in Mombasa, Kenya, followed from the time of HIV-1 infection. METHODS: At monthly follow-up visits, sexual behavior and contraceptive use were recorded, and laboratory screening for STI was performed. Multivariate Andersen-Gill proportional hazards models were constructed to examine the association between the use of hormonal contraception and the occurrence of cervical STI. RESULTS: The median duration of follow-up after HIV-1 acquisition was 35 months, and 799 person-years of follow-up were accrued. After adjustment for demographic factors and sexual behavior, women using the injectable contraceptive depot medroxyprogesterone acetate were at increased risk of Chlamydia trachomatis infection [hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.4, P = 0.05] and cervicitis (HR 1.6, 95% CI 1.0-2.3, P = 0.03) compared with women using no contraception. The use of oral contraceptive pills was associated with an increased risk of cervicitis (HR 2.3, 95% CI 1.4-3.8, P = 0.001). Hormonal contraception was not associated with an increased risk of infection with Neisseria gonorrhoeae. CONCLUSION: The use of hormonal contraception by HIV-1-infected women was associated with an increased risk of cervicitis and cervical chlamydia infection. HIV-1-seropositive women using hormonal contraception should be counseled about the importance of consistent condom use to prevent both STI and HIV-1 transmission.