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Biomedical subjects

N B Kiviat

Publications and source records attributed to N B Kiviat.

At least 19 recordsLinked to original sources
PubMed2004

The antimicrobial treatment of subacute endometritis: a proof of concept study.

OBJECTIVE: Our purpose was to evaluate the antimicrobial therapy effect on clinical and laboratory findings among women at risk for endometritis. STUDY DESIGN: A prospective antimicrobial treatment trial of 153 women was performed to characterize subacute endometritis and to determine the treatment effect on endometritis resolution. RESULTS: After antimicrobial treatment, significant reductions occurred in abnormal bleeding (60% vs 29%), mucopurulent cervicitis (20% vs 6%), uterine tenderness (20% vs 6%), and histologic endometritis (38% vs 4%), all P<.001. In women with prior pelvic inflammatory disease (PID), endometritis was present in 43% with and 28% without current Chlamydia trachomatis or Neisseria gonorrhoeae. In women without prior PID, endometritis was present in 23% with and 12% without current C trachomatis or N gonorrhoeae (P=.002 for trend). CONCLUSIONS: In women without a clinical diagnosis of PID, antimicrobial therapy decreased abnormal clinical findings and histologic endometritis. Prior PID is additive with current cervical infection as a risk for endometritis.

Adult↗
PubMed2004

Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal.

Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T-cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients to determine if differences relate to more efficient HIV-2 control. Homologous HIV-specific T cells were detected in similar frequencies (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection, respectively. Gag-specific responses predominated in both groups (>/=64%), and significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the mean magnitude was similar. Total frequencies of HIV-specific responses in both groups did not correlate with plasma viral load and CD4(+) T-cell count in multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific responses was significantly associated with lower plasma viremia in HIV-1-infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1-infected patients. These findings indicate that improved control of HIV-2 infection may relate to the contribution of T-helper cell responses. By contrast, the superior control of HIV-1 replication associated with HIV-2 Gag responses suggests that these may represent cross-reactive, higher-avidity T cells targeting epitopes within Gag regions of functional importance in HIV replication.

Adolescent↗
PubMed2001

Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women.

OBJECTIVES: The purpose of this study was to examine frequency of and attitudes toward Papanicolaou (Pap) test screening in women who have sex with women (WSW) and to determine prevalence of genital human papillomavirus (HPV). METHODS: Women were eligible if they reported having engaged in sex with another woman in the preceding year Medical and sexual histories were obtained. Cervical specimens for Pap tests and cervical and vaginal specimens for HPV DNA testing were collected. RESULTS: HPV DNA was detected in 31 of 248 WSW (13%). Women who had never had sex with men were less likely to have undergone pelvic examinations and had fewer recent Pap tests. Reasons for not undergoing Pap tests included lack of insurance, previous adverse experiences, and belief that Pap tests were unnecessary. CONCLUSIONS: Despite the occurrence of genital HPV, WSW do not receive adequate Pap test screening. Pap test screening recommendations should not differ for WSW, regardless of sexual history with men.

Adult↗
PubMed2001

HLA class II DR-DQ and increased risk of cervical cancer among Senegalese women.

To examine Senegalese women to confirm and extend associations between HLA class II types and cervical cancer previously observed among African-American, Caucasian, Hispanic, and Japanese ethnic populations, 55 Senegalese women with invasive cervical carcinoma were compared with age-matched (human papillomavirus) HPV-positive (n = 83) and HPV-negative (n = 107) control women. PCR-based HPV and HLA typing methods were used. Data were analyzed using a global randomization test and conditional logistic regression. Although this study failed to confirm a previously reported association between cervical cancer and DQB1*03 alleles, the DRB1*1101-DQB1*0301 haplotype was detected more frequently among cervical carcinoma cases than among controls (adjusted odds ratio, 2.6; 95% confidence interval, 1.0-7.1). Furthermore, as reported by others, we observed a negative association of borderline statistical significance between DRB1*13 and cervical carcinoma (adjusted odds ratio, 0.5; 95% confidence interval, 0.2-1.1). Observations from this study confirm earlier findings of a negative association between DRB1*13 and cervical cancer and suggest that specific DRB1-DQB1 haplotype combinations, rather than individual DQB1*03 alleles, increase the risk for cervical cancer.

Adult↗
PubMed2000

Concurrent and sequential acquisition of different genital human papillomavirus types.

Coinfection with multiple types of genital human papillomavirus (HPV) has been reported, but how frequently it occurs and whether prior infection with specific HPV types inhibits subsequent infection by related types are not known. To address this, 518 women were followed for an average of 2.9 years, and behavioral information and cervical and vulvovaginal swabs for HPV DNA assay were obtained at 4-month intervals. A polymerase chain reaction-based method was used to detect types frequently found in cervical cancers (HPV 16, 18, 31, and 45) and in genital warts (HPV 6 and 11). Concurrent acquisition of multiple types occurred more often than expected by chance. However, no 2 types were more or less likely to be acquired concurrently than any other 2 types. When considering sequential acquisition of HPV types, we found that risk of acquiring a new HPV type was not decreased among those with prior infection by a phylogenetically related or unrelated type (hazard ratio [95% confidence interval], 1.0 [0.4-3.0] and 1.3 [0.8-2.1], respectively).

Adolescent↗
PubMed2000

Detection of cervical antibodies to human papillomavirus type 16 (HPV-16) capsid antigens in relation to detection of HPV-16 DNA and cervical lesions.

A more sensitive luminescence immunoassay (LIA) for human papillomavirus type 16 (HPV-16) was developed and used to measure HPV-16 antibodies in cervical samples from 292 college-aged women who were examined at 4-month intervals. Of the 609 collected samples, IgG, IgA, and secretory piece-associated antibodies to HPV-16 were detected in 12%, 6%, and 8%, respectively, of samples tested. Cervical IgG antibodies were most strongly associated with HPV-16 DNA detected within the previous 12 months (odds ratio, 3.3; 95% confidence interval, 1.4-7.8). Secretory IgA (cervical IgA- and secretory piece-positive) was most strongly associated with detection of a squamous intraepithelial lesions 4-8 months earlier (odds ratio, 6.4; 95% confidence interval, 1.9-21.8). As with serum HPV-16 antibodies, there appears to be a several-month delay between cervical HPV infection and detection of cervical antibodies.

Adult↗
PubMed2000

Association of antiretroviral therapy with detection of HIV-1 RNA and DNA in the anorectal mucosa of homosexual men.

OBJECTIVE: To determine whether combination antiretroviral therapy is associated with reduced detection of HIV-1 RNA and DNA in the anorectal mucosa of men who have sex with men (MSM). DESIGN: Cross-sectional study of 233 MSM recruited from community and clinic sites in Seattle, Washington between July 1996 and December 1997. METHODS: HIV-1 RNA and HIV-1 DNA were detected in anorectal swab specimens by polymerase chain reaction amplification assays. RESULTS: HIV-1 RNA was detected significantly less often in anorectal specimens from users of combination antiretroviral therapies, whether a protease inhibitor was received (15/89; 17%) or not (16/53; 30%), than in men not receiving therapy (43/88; 49%) (P < 0.001, P = 0.03, respectively). In contrast, HIV-1 DNA was detected only slightly less frequently in anorectal specimens obtained from men receiving protease inhibitors (35/81; 43%) or reverse transcriptase inhibitors alone (22/48; 46%) than in specimens from men not receiving therapy (45/78; 58%) (P = 0.07, P = 0.20, respectively). Among men with < 50 copies HIV-1 RNA/ml plasma, detection of HIV-1 RNA in anorectal specimens was rare (1/54; 2%) but detection of HIV-1 DNA was common (14/50; 28%). CONCLUSIONS: Combination antiretroviral therapy is associated with reductions in HIV-1 RNA, but HIV-1 DNA remains detectable in the anorectal canal of almost half of MSM receiving such therapy. Condom use during anal intercourse should be encouraged, regardless of plasma viral load response to potent antiretroviral therapy.

Adult↗
PubMed2000

Secretor polymorphism and human immunodeficiency virus infection in Senegalese women.

The FUT2 gene encodes the enzyme alpha (1,2) fucosyltransferase, which determines expression of blood-group antigens on mucosal epithelial cell surfaces and in secretions. Homozygotes for a specific stop mutation in FUT2 (nonsecretors) cannot produce this enzyme and thus are unable to express blood group antigens. Nonsecretor status is associated with a decreased risk of several respiratory viral infections. By use of molecular genotyping, 2 populations of Senegalese women were examined for polymorphisms of the FUT2 gene. Among Senegalese commercial sex workers, absence of FUT2 (nonsecretor genotype) was associated with reduced risk of human immunodeficiency virus (HIV) type 1 infection (odds ratio [OR] adjusted for cervical and vaginal infection, 0.18; 95% confidence interval [CI], 0.04-0.90) and HIV-2 infection (adjusted OR, 0.43; 95% CI, 0.13-1.39), although the latter was not statistically significant. Modification of cell surface carbohydrates at mucosal surfaces determined by the FUT2 gene may underlie the protective association against heterosexual HIV infection.

Adult↗
PubMed2000

Etiology of genital ulcer disease in Dakar, Senegal, and comparison of PCR and serologic assays for detection of Haemophilus ducreyi.

We used PCR assays to determine the etiology of genital ulcers in patients presenting to a sexually transmitted disease clinic in Dakar, Senegal, and evaluated the ability of two PCR tests (groEL and recD) and two serological tests (adsorption enzyme immunoassay [EIA] and lipooligosaccharide [LOS] EIA) to detect current Haemophilus ducreyi infection. We found that in this population, H. ducreyi, T. pallidum, and herpes simplex virus HSV DNA were detected in 56, 15, and 13% of 39 genital ulcer specimens, respectively, and H. ducreyi DNA was detected in 60% (3 of 5) of samples from ulcerated bubos. Among 40 consecutive patients with genital ulcer disease and with sufficient sample for both PCR assays, the recD and groEL H. ducreyi PCR assays were 83% concordant, with the recD PCR assay detecting six (15%) additional positive specimens and the groEL assay detecting one (3%) additional positive specimen. Compared to PCR, the adsorption EIA and LOS EIA tests had sensitivities of 71 and 59% and specificities of 57 and 90%, respectively, for the diagnosis of current H. ducreyi infection. While these differences in specificity could be due either to previous infection with H. ducreyi or to the detection of cross-reacting antibodies, only 6% of patients from a nearby family planning clinic gave a positive reaction in both the adsorption EIA and LOS EIA assays, indicating that cross-reacting antibodies are not prevalent among clinic attendees in this city. Our studies indicate that the adsorption EIA detects both current and past infection, while the LOS EIA assay is more specific for current infection with H. ducreyi in this population.

Adult↗
PubMed1999

A matched prospective study of human immunodeficiency virus serostatus, human papillomavirus DNA, and cervical lesions detected by cytology and colposcopy.

OBJECTIVE: To compare the prevalence and type of human papillomavirus (HPV) infections in the genital tract of human-immunodeficiency-virus- (HIV) seropositive and -seronegative women matched for cytology and to examine prospectively the relationship of HPV DNA, colposcopic findings and cervical squamous intraepithelial lesions (SIL) in these matched seropositive and seronegative cohorts. METHODS: A matched prospective study of HIV-seropositive and -seronegative women undergoing cytologic screening, colposcopy, and testing for HPV DNA and other infections at each visit. RESULTS: Twenty-three HIV-seropositive women were matched with 23 seronegative women by cervical cytology reading, lifetime number of sexual partners, age, and follow-up length. Fourteen pairs of these women had follow-up visits every 4 months, for 56 and 53 total visits in seropositive and seronegative women, respectively. After matching, the groups had a similar overall prevalence of HPV DNA and of HPV oncogenic (high risk) types at baseline. On follow up, HIV-seropositive women were more likely than seronegative women to develop SIL (38% vs. 10%), less likely to have negative cytology (34% vs. 60%, overall P = 0.03), more visits with HPV DNA detected (68% vs. 40% P = 0.04), and more visits with multiple HPV DNA types detected (18% vs. 0%, P = 0.02). Colposcopic lesions in the seropositive women were more likely to have sharp borders or mosaicism or to be thick white (P = 0.009). CONCLUSIONS: After matching for baseline Papanicolaou smear readings, these data suggest that over time seropositive women have more visits that yield abnormal cytology, more persistent HPV DNA detection, and more colposcopic abnormalities than seronegative women.

Adult↗
PubMed1999

Papillomaviruses in non-melanoma skin cancer: epidemiological aspects.

Worldwide, non-melanoma skin cancers (NMSCs), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are the most commonly diagnosed cancers among Caucasians. It is well established that ultraviolet radiation (UVR) plays a central role in the development of these cancers, and more recently, a role for specific genetic mutations in the pathogenesis of BCC has been identified. The possibility that certain types of HPV, either alone or in conjunction with UVR, may play a role in the pathogenesis of these cancers is suggested by several lines of evidence reviewed below.*9 @2depidemiology / non-melanoma skin cancer / papillomavirus

Chromosomes, Human, Pair 9↗
PubMed1999

Comparison of variant-specific hybridization and single-strand conformational polymorphism methods for detection of mixed human papillomavirus type 16 variant infections.

PCR-based variant-specific hybridization (VSH) and single-strand conformational polymorphism (SSCP) analyses were compared for their capacities to detect mixed human papillomavirus type 16 (HPV-16) variant infections within clinical specimens. The SSCP assay used in this comparison targets a 682-bp fragment that spans nucleotides 7445 to 222 within the HPV-16 genome. This fragment includes portions of the HPV-16 long control region and the E6 open reading frame and identifies three categories of SSCP patterns: those identical to the patterns of prototype HPV-16 (P), those identical to the patterns of Caski-derived HPV-16 (C), or those that are different from the P and C HPV-16 patterns and that are therefore classified as belonging to novel (N) HPV-16 variants. VSH targets the entire HPV-16 E6-coding region (nucleotides 56 to 640) and distinguishes previously described variant nucleotides at positions 109, 131, 132, 143, 145, 178, 286, 289, 350, 403, and 532. Clinical samples used in VSH and SSCP analyses were subjected to multiple independent amplification reactions. The resultant amplicons were cloned, and 14 to 78 clones per clinical specimen were evaluated by VSH. VSH detected an HPV-16 variant that represented at least 20% of the amplified HPV-16 variant population. In contrast, SSCP analysis detected HPV-16 variants that represented 36% of the amplified HPV-16 population. Comparison studies were conducted with mixed HPV-16 variant laboratory constructs. Again, VSH had a higher sensitivity than SSCP analysis in detecting mixed HPV-16 variant infections in these constructed amplicon targets. Accurate detection of HPV-16 variants may enhance our understanding of the natural history of HPV-16 infections.

Base Sequence↗
PubMed1998

Risk of anal carcinoma in situ in relation to human papillomavirus type 16 variants.

Infection with human papillomavirus (HPV), especially HPV16, is central to the development of squamous anogenital cancers and their precursor lesions, termed "squamous intraepithelial neoplasias." Men who have sex with men, particularly those who are infected with HIV, are at a high risk for anal infection with HPV16 and for low-grade anal neoplasia; however, only a subset of these men develop anal invasive cancer or its immediate precursor lesion, anal carcinoma in situ (CIS). To examine the hypothesis that certain variants of HPV16 are most strongly associated with development of anal CIS, we followed 589 men who have sex with men whose initial anal cytological smears did not show anal CIS. Anoscopy, anal cytology, and PCR-based assays for detection and classification of HPV types were performed every 4-6 months, with HPV16 further classified by single-stranded conformation polymorphism analysis as being a prototype-like (PL) or non-prototype-like (NPL) variant. Anal CIS was histologically confirmed in 6 of 384 (1.6%) consistently HPV16-negative men, in 12 of 183 (6.6%) men with HPV16 PL variants, and in 4 of 22 (18.2%) men with HPV16 NPL variants. After adjustment for anal cytological diagnoses at study entry, HIV status and CD4 count, and detection of HPV types other than type 16, men with HPV16 NPL variants were 3.2 times (95% confidence interval, 1.0-10.3) more likely to develop anal CIS than were those with PL variants. Neither detection of HPV16 DNA at high levels nor detection of HPV16 DNA for a prolonged period, factors that we previously demonstrated to be associated with risk of high-grade anal squamous intraepithelial neoplasia, was significantly associated with HPV16 NPL variants. The biological mechanism relating to Ihis excess risk remains undetermined.

Anus Neoplasms↗
PubMed1998

Effect of HIV infection on the natural history of anal human papillomavirus infection.

OBJECTIVE: To identify risk factors for the detection of prevalent and incident anal human papillomavirus (HPV) infection, and HPV persistence among HIV-seropositive and seronegative homosexual men. DESIGN: Longitudinal study of 287 HIV-seronegative and 322 HIV-seropositive men attending a community-based clinic. METHODS: Subjects underwent an interview and examination; specimens were collected for HIV serology and assessment of anal HPV and HIV DNA. RESULTS: Anal HPV DNA was detected at study entry in 91.6% of HIV-infected men, and 65.9% of men not infected with HIV. HPV detection was associated with lifetime number of sexual partners and recent receptive anal intercourse (HIV-seronegative men), decreased CD4+ lymphocyte count (HIV-seropositive men), and anal warts (all men). Among men negative for HPV at study entry, subsequent detection of HPV was associated with HIV, unprotected receptive anal intercourse, and any sexual contact since the last visit. Among men positive for HPV at study entry, subsequent detection of additional HPV types was more common among HIV-seropositive men. Becoming HPV negative during follow-up was less common among men with HIV or high HPV levels at study entry. Among those with HIV, HPV persistence was associated with presence of anal HIV DNA, but not with CD4+ lymphocyte count. CONCLUSIONS: Risk of anal HPV infection appears to increase with sexual exposure, epithelial trauma, HIV infection and immune deficiency. Incident infection may result from recent sexual exposure or reactivation of latent infection. Further studies are needed to elucidate the mechanism by which HIV DNA in the anal canal increases the risk of HPV persistence.

Adult↗
PubMed1998

Low risk of perinatal transmission of human papillomavirus: results from a prospective cohort study.

OBJECTIVE: Our purpose was to evaluate the risk of perinatal transmission of human papillomavirus. STUDY DESIGN: Pregnant women were evaluated at <20 weeks' and between 34 and 36 weeks' gestation for genital human papillomavirus by clinical and colposcopic examination and by polymerase chain reaction. Their 151 infants were evaluated at birth, 6 weeks, and 6, 12, 18, 24, and 36 months of age for detection of human papillomavirus deoxyribonucleic acid by polymerase chain reaction on samples from the mouth, external genitalia, and anus. Polymerase chain reaction was performed with human papillomavirus L1 consensus primers and hybridization to human papillomavirus types 6, 11, 16, 18, 31, 33, 35, 39, and 45 and to a generic probe. RESULTS: During pregnancy 112 (74%) of 151 women had historic, clinical, or deoxyribonucleic acid evidence of genital human papillomavirus infection. At 479 infant visits, human papillomavirus deoxyribonucleic acid was detected from only five (1.5%) of the 335 genital, four (1.2%) of the 324 anal, and none of the 372 oral or nasopharyngeal specimens. A positively reacting specimen was obtained from three (4%) of 80 infants born to women with human papillomavirus deoxyribonucleic acid detected at 34 weeks' gestation and from five (8%) of 63 born to women without human papillomavirus deoxyribonucleic acid (p = 0.47). All positive results in the infants were positive only with the generic probe and were preceded or followed by negatively reacting specimens. No clinical manifestations of human papillomavirus infection were detected in any infant. CONCLUSIONS: The isolated detection of unclassified human papillomavirus types from infants at only single visits may represent low-level genital or nongenital human papillomavirus or may represent contamination. Although perinatal transmission of human papillomavirus is not ruled out by these data, the upper 95% confidence interval for detection of perinatal transmission from women with any evidence of genital human papillomavirus was only 2.8%.

Adolescent↗
PubMed1998

Genital human papillomavirus infection in women who have sex with women.

Genital infection with human papillomavirus (HPV), as determined by polymerase chain reaction detection of HPV DNA and prevalence of HPV-6 and -16 serum antibodies, was investigated in 149 women who were sexually active with women. By use of HPV L1 consensus primers and hybridization to types 6/11, 16, 18, 31/33/35/39, and 45 and a generic probe, HPV DNA was detected in 30% of subjects; of these, 20% had type 31/33/35/39, 18% had type 16, and 2% had type 6/11. Of 21 subjects reporting no prior sex with men, HPV DNA was detected in 19% and squamous intraepithelial lesions in 14%. By capture ELISA with HPV-6 and -16 L1 capsids, 47% of subjects were seropositive for HPV-16 and 62% for HPV-6. Current smoking was associated with detectable HPV DNA. Genital HPV infection and squamous intraepithelial lesions are common among women who are sexually active with women and occur among those who have not had sex with men.

Adult↗
PubMed1998

Determinants of human immunodeficiency virus DNA and RNA shedding in the anal-rectal canal of homosexual men.

To define the determinants of anal-rectal shedding of human immunodeficiency virus (HIV) DNA and RNA, 374 HIV-seropositive homosexual men were tested. Factors independently associated with detection of anal-rectal HIV DNA included anal-rectal inflammation and detection of anal human papillomavirus DNA; predictors of HIV RNA included detection of anal-rectal HIV DNA, anal-rectal inflammation, and high plasma HIV RNA levels. The latter (>10,000 copies/mL) was the main determinant of anal-rectal HIV RNA shedding when HIV DNA (e.g., HIV-infected cells) was not detected in the anal-rectal sample. The local presence of HIV-infected cells and local inflammation were the principal determinants of HIV RNA among those with low (<10,000 copies/mL) plasma HIV RNA load. Among those with anal-rectal HIV DNA present, increased HIV RNA plasma load did not increase the risk of shedding of HIV RNA into the anal-rectal canal.

Adolescent↗