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1.
J Infect Dis ; 219(7): 1067-1075, 2019 03 15.
Article in English | MEDLINE | ID: mdl-30395247

ABSTRACT

BACKGROUND: Little is known about the epidemiology of ß and γ human papillomaviruses (HPVs) in oral cavities of healthy women. METHODS: We performed multiplex polymerase chain reaction analysis for detection of 46 ß-HPVs and 51 γ-HPVs in stored oral rinse samples from healthy mid-adult women (age, 30-50 years). A total of 407 women were tested for ß-HPVs, and 310 were tested for γ-HPVs. We used log-binomial regression to identify determinants of ß-HPV and γ-HPV in separate models. Using paired fingernail data from a subset of 184 women, we also evaluated whether fingernail ß-HPV detection was associated with concurrent detection of the same type in the oral cavity. RESULTS: Oral HPV prevalence was 20.6% for ß-HPV and 10.7% for γ-HPV. In multivariate analysis, oral ß-HPV detection was associated with increasing age (adjusted prevalence ratio [aPR] per 5-year difference, 1.37; 95% confidence interval [CI], 1.01-1.86) and a greater lifetime number of oral sex partners (aPR for reporting ≥6 vs 0-5 partners, 2.06; 95% CI, 1.01-4.20). In a separate model, concurrent detection of the same ß-HPV type in fingernails was strongly associated with oral ß-HPV detection (aPR, 31.44; 95% CI, 19.81-49.49). No significant determinants of γ-HPV detection were identified. CONCLUSIONS: Our results suggest a sexual transmission route for ß-HPVs and support the hypothesis that fingers may serve as a source of transmission or autoinoculation of ß-HPVs to the oral cavity.


Subject(s)
Betapapillomavirus , Carrier State/epidemiology , Carrier State/virology , Gammapapillomavirus , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Adult , Betapapillomavirus/genetics , Female , Gammapapillomavirus/genetics , Genotype , Humans , Male , Mouth/virology , Nails/virology , Prevalence , Risk Factors , Sexual Behavior , Sexual Partners
2.
J Infect Dis ; 219(6): 908-915, 2019 02 23.
Article in English | MEDLINE | ID: mdl-30321371

ABSTRACT

BACKGROUND: High-risk human papillomavirus (hrHPV) causes cervical cancer. In the United States, approximately 40% of women aged 14-59 years from all racial and ethnic groups are infected with HPV, and prevalence typically declines with age. However, American Indian (AI) women are insufficiently sampled to permit a population-specific estimate of hrHPV prevalence. METHODS: Vaginal swabs were self-collected by 698 AI women aged 21-65 years from a tribal community in the Great Plains. We estimated the population prevalence of hrHPV and identified predominant genotypes. RESULTS: The combined prevalence of hrHPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 was 34.8%. HPV-51 (7.6%), HPV-58 (5.3%), HPV-52 (4.3%), HPV-18 (4.3%), and HPV-16 (3.9%) were most prevalent. hrHPV prevalence declined with age, from 42.2% in women aged 21-24 years to 27.9% in women aged 50-65 years. CONCLUSIONS: HPV-51 was the single most prevalent oncogenic genotype. The combined prevalence of hrHPV among AI women in our sample was high, particularly among women aged 50-65 years, for whom hrHPV prevalence was approximately triple that of other races. Cervical cancer screening efforts should be increased, particularly among women from the community aged 30 years and older.


Subject(s)
Indians, North American , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Adult , Aged , Female , Genotype , Humans , Middle Aged , Midwestern United States/epidemiology , Papillomaviridae/genetics , Papillomavirus Infections/ethnology , Papillomavirus Infections/virology , Prevalence
3.
J Community Health ; 41(5): 1049-61, 2016 10.
Article in English | MEDLINE | ID: mdl-27048284

ABSTRACT

We evaluated the feasibility and acceptability of self-sampling for human papillomavirus (HPV) testing and calculated the prevalence of and risk factors for high-risk (hr) HPV infections in a community-based sample of American Indian women. To this end, we recruited 329 Hopi women aged 21-65 years to self-collect vaginal samples for hrHPV testing. Samples were tested by polymerase chain reaction for 14 hrHPV genotypes. We used Chi square tests to identify correlates of preference for clinician Pap testing versus HPV self-sampling, and age-adjusted Poisson regression to evaluate correlates of hrHPV prevalence. We found that satisfaction with HPV self-sampling was high, with 96 % of women reporting that the sample was easy to collect and 87 % reporting no discomfort. The majority (62 %) indicated that they preferred HPV self-sampling to receiving a Pap test from a clinician. Preference for Pap testing over HPV self-sampling was positively associated with adherence to Pap screening and employment outside the home. All samples evaluated were satisfactory for HPV testing, and 22 % were positive for hrHPV. HrHPV prevalence peaked in the late 20 s and declined with increasing age. HrHPV positivity was inversely associated with having children living the household. In conclusion, HPV self-sampling is feasible and acceptable to Hopi women, and could be effective in increasing rates of cervical cancer screening in Hopi communities. HrHPV prevalence was similar to estimates in the general United States population.


Subject(s)
Indians, North American , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Patient Acceptance of Health Care , Self Care , Specimen Handling , Adult , Aged , Feasibility Studies , Female , Humans , Middle Aged , Risk Factors , Surveys and Questionnaires , Uterine Cervical Neoplasms/prevention & control , Young Adult
4.
Nat Med ; 29(12): 3224-3232, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38049621

ABSTRACT

Cervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15-20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3-99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0-99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0-98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256 .


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Female , Humans , Human papillomavirus 16 , Human papillomavirus 18 , Kenya/epidemiology , Papillomaviridae , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/adverse effects , Persistent Infection , Uterine Cervical Neoplasms/prevention & control , Vaccination/methods , Double-Blind Method
5.
NEJM Evid ; 1(5): EVIDoa2100056, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35693874

ABSTRACT

Background: Single-dose HPV vaccination, if efficacious, would be tremendously advantageous; simplifying implementation and decreasing costs. Methods: We performed a randomized, multi-center, double-blind, controlled trial of single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) or bivalent (HPV 16/18) HPV vaccination compared to meningococcal vaccination among Kenyan women aged 15-20 years. Enrollment and six monthly cervical swabs and a month three vaginal swab were tested for HPV DNA. Enrollment sera were tested for HPV antibodies. The modified intent-to-treat (mITT) cohort comprised participants who tested HPV antibody negative at enrollment and HPV DNA negative at enrollment and month three. The primary outcome was incident persistent vaccine-type HPV infection by month 18. Results: Between December 2018 and June 2021, 2,275 women were randomly assigned and followed; 758 received the nonavalent HPV vaccine, 760 the bivalent HPV vaccine, and 757 the meningococcal vaccine; retention was 98%. Thirty-eight incident persistent infections were detected in the HPV 16/18 mITT cohort: one each among participants assigned to the bivalent and nonavalent groups and 36 among those assigned to the meningococcal group; nonavalent Vaccine Efficacy (VE) was 97.5% (95%CI 81.7-99.7%, p=<0.0001), and bivalent VE was 97.5% (95%CI 81.6-99.7%, p=<0.0001). Thirty-three incident persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: four in the nonavalent group and 29 in the meningococcal group; nonavalent VE for HPV 16/18/31/33/45/52/58 was 88.9% (95%CI 68.5-96.1%, p<0.0001). The rate of SAEs was 4.5-5.2% by group. Conclusions: Over the 18 month time-frame we studied, single-dose bivalent and nonavalent HPV vaccines were each highly effective in preventing incident persistent oncogenic HPV infection, similar to multidose regimens.

6.
Trials ; 22(1): 661, 2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34579786

ABSTRACT

BACKGROUND: HPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule. METHODS: We are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15-20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models. DISCUSSION: This study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03675256 . Registered on September 18, 2018.


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Adolescent , Child , Female , Human papillomavirus 16 , Human papillomavirus 18 , Humans , Kenya , Papillomavirus Infections/prevention & control , Randomized Controlled Trials as Topic , Uterine Cervical Neoplasms/prevention & control , Vaccination , Young Adult
7.
J Clin Microbiol ; 48(9): 3068-72, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20610686

ABSTRACT

We determined the feasibility of human papillomavirus (HPV) detection in cervical exfoliated cells collected as dry swab samples. Both dry cervical swab and specimen transport medium (STM) cervical swab samples were collected from 135 patients attending either colposcopy or women's clinics in Guayaquil, Ecuador, who had a cytology diagnosis within 6 months. HPV was detected by dot blot hybridization and genotyped by the liquid bead microarray assay (LBMA). Overall, 23.1% of dry samples were positive for any high-risk HPV types, and 24.6% of STM samples were positive for any high-risk HPV types. Of 125 paired samples, the type-specific high-risk HPV proportion positive agreement was 60.7% (kappa, 0.69; 95% confidence interval [CI], 0.53 to 0.82). Of six women with cytological evidence of invasive cervical cancer, high-risk HPV DNA was detected in three of their STM samples and in five of their dry samples. Dry samples were more likely to be insufficient for HPV testing than STM samples. Consistent with this observation, the amount of genomic DNA quantitated with the beta-actin gene was almost 20 times lower in dry samples than in STM samples when detected by the real-time TaqMan assay; however, HPV DNA viral loads in dry samples were only 1.6 times lower than those in matched STM samples. We concluded that exfoliated cervical cells could be collected as dry swab samples for HPV detection.


Subject(s)
Cervix Uteri/virology , Desiccation , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Specimen Handling/methods , Virology/methods , Adult , DNA, Viral/genetics , DNA, Viral/isolation & purification , Ecuador , Female , Humans , Middle Aged , Molecular Diagnostic Techniques/methods , Papillomaviridae/classification , Papillomaviridae/genetics , Sensitivity and Specificity
8.
Clin Infect Dis ; 48(4): 476-83, 2009 Feb 15.
Article in English | MEDLINE | ID: mdl-19143530

ABSTRACT

BACKGROUND: The efficacy of various antiretroviral (ARV) therapy regimens for human immunodeficiency virus type 2 (HIV-2) infection remains unclear. HIV-2 is intrinsically resistant to the nonnucleoside reverse-transcriptase inhibitors and to enfuvirtide and may also be less susceptible than HIV-1 to some protease inhibitors (PIs). However, the mutations in HIV-2 that confer ARV resistance are not well characterized. METHODS: Twenty-three patients were studied as part of an ongoing prospective longitudinal cohort study of ARV therapy for HIV-2 infection in Senegal. Patients were treated with nucleoside reverse-transcriptase inhibitor (NRTI)- and PI (indinavir)-based regimens. HIV-2 pol genes from these patients were genotyped, and the mutations predictive of resistance in HIV-2 were assessed. Correlates of ARV resistance were analyzed. RESULTS: Multiclass drug-resistance mutations (NRTI and PI) were detected in strains in 30% of patients; 52% had evidence of resistance to at least 1 ARV class. The reverse-transcriptase mutations M184V and K65R, which confer high-level resistance to lamivudine and emtricitabine in HIV-2, were found in strains from 43% and 9% of patients, respectively. The Q151M mutation, which confers multinucleoside resistance in HIV-2, emerged in strains from 9% of patients. HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, and T215Y/F) were not observed, with the exception of K70R, which was present together with K65R and Q151M in a strain from 1 patient. Eight patients had HIV-2 with PI mutations associated with indinavir resistance, including K7R, I54M, V62A, I82F, L90M, L99F; 4 patients had strains with multiple PI resistance-associated mutations. The duration of ARV therapy was positively associated with the development of drug resistance (P = .02). Nine (82%) of 11 patients with HIV-2 with no [corrected] detectable ARV resistance had undetectable plasma HIV-2 RNA loads (<1.4 log(10) copies/mL), compared with 3 (25%) of 12 patients with HIV-2 with detectable ARV resistance (P = .009). Patients with ARV-resistant virus had higher plasma HIV-2 RNA loads, compared with those with non-ARV-resistant virus (median, 1.7 log(10) copies/mL [range, <1.4 to 2.6 log(10) copies/mL] vs. <1.4 log(10) copies/mL [range, <1.4 to 1.6 log(10) copies/mL]; P = .003). CONCLUSIONS: HIV-2-infected individuals treated with ARV therapy in Senegal commonly have HIV-2 mutations consistent with multiclass drug resistance. Additional clinical studies are required to improve the efficacy of primary and salvage treatment regimens for treating HIV-2 infection.


Subject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV-2/drug effects , Adult , Amino Acid Substitution/genetics , Anti-HIV Agents/pharmacology , Female , HIV Reverse Transcriptase/genetics , HIV-2/isolation & purification , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation, Missense , Phylogeny , Senegal , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Viral Load
9.
J Clin Microbiol ; 47(3): 547-53, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19144800

ABSTRACT

We developed a liquid bead microarray (LBMA) assay for genotyping genital human papillomaviruses (HPVs) based on the MY09-MY11-HMB01 PCR system and the reverse line blot (RLB) assay probe sequences. Using individual HPV plasmids, we were able to detect as few as 50 copies per reaction. In two separate retrospective studies, the LBMA assay was compared to the RLB assay and to the Hybrid Capture II (hc2) assay. Testing was performed without knowledge of other assay results. In the first study, 614 cervical swab samples (enriched for HPV infection) from 160 young women were tested for HPV DNA, and 360 (74.8%) type-specific HPV infections were detected by both assays, 71 (14.8%) by the LBMA assay only, and 50 (10.4%) by the RLB assay only. Type-specific agreement for the two assays was excellent (99.1%; kappa=0.85; 95% confidence interval [95% CI], 0.82 to 0.88). Samples with discrepant LBMA and RLB test results tended to have low viral loads by a quantitative type-specific PCR assay. In the second study, cervical swab samples from 452 women (including 54 women with histologically confirmed cervical-intraepithelial neoplasia grade 2 or worse [>or= CIN2]) were tested initially by the hc2 and subsequently by the LBMA assay. The estimated sensitivities for >or= CIN2 were similar for the LBMA and hc2 assays (98.4% [95% CI, 95.0 to 100%] and 95.6% [95% CI, 89.2 to 100%], respectively). The percentages of negative results among 398 women without >or= CIN2 were similar for the LBMA and hc2 assays (45% and 50%, respectively). The repeat test reproducibility for 100 samples was 99.1% (kappa=0.92; 95% CI, 0.90 to 0.95). We conclude that the new LBMA assay will be useful for clinical and epidemiological research.


Subject(s)
Microarray Analysis/methods , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , Adolescent , Adult , Cervix Uteri/virology , DNA, Viral/genetics , Female , Genotype , Humans , Microspheres , Nucleic Acid Hybridization/methods , Papillomaviridae/genetics , Polymerase Chain Reaction/methods , Reproducibility of Results , Sensitivity and Specificity , Young Adult
10.
Papillomavirus Res ; 5: 1-5, 2018 06.
Article in English | MEDLINE | ID: mdl-29807613

ABSTRACT

Cutaneous human papillomaviruses (HPVs) have not been evaluated in fingernails from healthy individuals. To determine prevalence and correlates of ß-HPVs in fingernails from healthy mid-adult women, we tested archived samples collected from 2011 to 2012 using a multiplex PCR combined with Luminex technology for 46 ß-HPV genotypes. One hundred thirteen (61.1%) of 185 fingernail samples were positive for ß-HPV, and the median number of types detected in positive samples was 2 (interquartile range: 1-4). The most common genotypes detected were HPV-23 (ß-2) (13.5%), HPV-38 (ß-2) (13.0%), HPV-5 (ß-1) (9.2%), HPV-107 (ß-2) (8.7%), and HPV-120 (ß-2) (8.7%). In multivariate analysis, ß-HPV detection was associated with age (prevalence ratio [PR] for women 40-51 years versus 30-39 years = 1.30, 95% CI: 1.05-1.62) and race (PR for non-white versus white race = 0.65, 95% CI: 0.45-0.94). The prevalence of ß-HPV in fingernail samples from healthy mid-adult women was similar to the prevalence of ß-HPV reported at other cutaneous sites in prior studies. We did not identify any significant health or sexual behavior predictors of ß-HPV detection in fingernails. Our results support the hypothesis that fingers may serve as a source of transmission or autoinoculation of cutaneous HPVs to other anatomic sites.


Subject(s)
Betapapillomavirus/isolation & purification , DNA, Viral/isolation & purification , Nails/virology , Papillomavirus Infections/diagnosis , Adult , Age Factors , Betapapillomavirus/genetics , Biological Specimen Banks , Female , Genotype , Healthy Volunteers , Humans , Middle Aged , Multiplex Polymerase Chain Reaction , Papillomavirus Infections/epidemiology , Prevalence , Risk Factors , Sexual Behavior
11.
Cancer Epidemiol ; 38(4): 369-75, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24852136

ABSTRACT

BACKGROUND: The importance of human papillomavirus (HPV) viral load in the pathogenesis of cervical cancer among HIV-infected and HIV-uninfected women has not yet been established. METHODS: In this cross-sectional study, HPV-16 viral loads were measured using previously-collected and frozen cervical swab samples from 498 HPV-16 positive Senegalese women (368 HIV-seronegative, 126 HIV-1 and/or HIV-2 seropositive). The real-time polymerase chain reaction assay was used to quantify HPV-16 E7 copy number normalized by human cellular DNA (ß-actin), and viral loads were log10 transformed. Associations between HPV-16 viral load, degree of cervical abnormality, and HIV status were assessed using multinomial and linear regression methods. RESULTS: Compared to women with normal cytology, the likelihood of CIN1 (ORa: 1.21, 95% CI 0.93-1.57), CIN2-3 (ORa: 2.38, 95% CI 1.72-3.29) and cancer (ORa: 2.12, 95% CI 1.52-2.96) was found to increase for each 1-unit log10 increase in HPV-16 viral load. Compared to HIV-negative women, HIV-positive women had higher average HPV-16 viral load values (ßa: 0.39, 95% CI 0.03-0.75), even after accounting for degree of cervical abnormality. CONCLUSION: In our study of women including those with cancer, HPV-16 viral load was associated with a higher likelihood of cervical abnormalities. However, substantial overlaps across categories of disease severity existed. Higher viral load among HIV-infected individuals may indicate that HIV infection influences HPV viral replication factors.


Subject(s)
HIV Infections/complications , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virology , Viral Load , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Human papillomavirus 16 , Humans , Middle Aged , Papillomavirus Infections/complications , Real-Time Polymerase Chain Reaction , Senegal , Young Adult
12.
Methods Mol Biol ; 903: 205-23, 2012.
Article in English | MEDLINE | ID: mdl-22782820

ABSTRACT

More than 100 human papillomavirus (HPV) types have been identified, and over 40 of them infect the anogenital epithelium. Because each HPV type is associated with different risks for the development of cervical cancer, detecting and genotyping HPVs has increasingly become an integral part of cervical cancer control. Here, we describe a Luminex assay-based liquid bead microarray assay for genotyping 37 HPV types, which is objective, scalable, amenable to a high-throughput configuration, and has the potential to be automated.


Subject(s)
Genotyping Techniques/methods , Microarray Analysis/methods , Microspheres , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , DNA, Viral/genetics , DNA, Viral/isolation & purification , Humans , Nucleic Acid Hybridization , Polymerase Chain Reaction
13.
J Clin Virol ; 55(2): 128-33, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22832059

ABSTRACT

BACKGROUND: Optimal care of persons infected with human immunodeficiency virus type 2 (HIV-2) requires an accurate assessment of HIV-2 plasma viral load (VL), but no clinically approved quantitative HIV-2 RNA VL assay exists. OBJECTIVES: To validate a novel quantitative HIV-2 RNA assay for clinical and research use. STUDY DESIGN: The Abbott m2000sp/rt platform was adapted for quantification of HIV-2 RNA in plasma. Amplification targeted a region of the long terminal repeat conserved in Group A and B HIV-2. Electron microscopy-counted-HIV-2 standards, the WHO/NIBSC HIV-2 International Standard and clinical specimens (N=162) were used to determine the precision, sensitivity, specificity, linear range, accuracy, and clinical performance of the assay. RESULTS: The quantitative linear range of the HIV-2 RNA assay was 10-1,000,000 copies/mL (R(2)>0.99), with a limit of detection of 8 copies/mL (95% CI, 5-18 copies/mL). The assay did not cross-react with HIV-1, and quantification of HIV-2 RNA was not affected by the presence of >5 log(10)HIV-1 RNA copies/mL. The total standard deviation (SD) and intra- and inter-run SD were 0.095, 0.093 and 0.162, respectively, at nominal inputs of 3.7, 1.7 and 1.0 log(10)HIV-2 RNA copies/mL. The HIV-2 WHO/NIBSC International Standard (1000 IU) was shown to contain 152 RNA copies/mL (95% CI 141-163). Overall, HIV-2 RNA was quantified at ≥10 copies/mL from 86 (53%) clinical specimens (median, 2.24 log(10) copies/mL; range 10-16,870), and nine specimens (6%) had HIV-2 RNA detected at <10 copies/mL. CONCLUSIONS: We developed and validated a highly sensitive HIV-2 VL assay that is suitable for clinical and research use.


Subject(s)
HIV Infections/virology , HIV-2/isolation & purification , Plasma/virology , RNA, Viral/blood , Viral Load/methods , Humans , Sensitivity and Specificity
14.
Cancer Epidemiol Biomarkers Prev ; 20(4): 699-707, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21173170

ABSTRACT

BACKGROUND: Characterizing short-term detection patterns of young women's incident α-genus human papillomavirus (HPV) infections may further our understanding of HPV transmission. METHODS: Between 2000 and 2007, we followed 18- to 22-year-old female university students with triannual HPV DNA and Papanicolaou testing. Using Kaplan-Meier methods, we estimated duration of detectable, type-specific incident infections; time to redetection (among infections that became undetectable); and time to cervical lesion development after incident infection. We evaluated risk factors for short-term persistent versus transient infection with logistic regression. RESULTS: Three hundred three incident, type-specific infections were detected in 85 sexually active women. Median time to first negative test after incident infection was 9.4 (95% CI: 7.8-11.2) months; 90.6% of infections became undetectable within 2 years. About 19.4% of infections that became undetectable were redetected within 1 year. Cervical lesions were common and 60% were positive for multiple HPV types in concurrent cervical swabs. Incident HPV detection in the cervix only (vs. the vulva/vagina only or both sites) was associated with short-term transience. CONCLUSIONS: Although most incident infections became undetectable within 2 years, redetection was common. Cervical lesions were a common early manifestation of HPV infection. IMPACT: It remains unclear whether potentially modifiable risk factors can be identified to reduce infection duration (and transmission likelihood).


Subject(s)
Papillomavirus Infections/epidemiology , Sexual Behavior/statistics & numerical data , Adolescent , Adult , Female , Humans , Incidence , Papillomavirus Infections/virology , Risk Factors , Uterine Cervical Diseases/epidemiology , Uterine Cervical Diseases/virology , Young Adult
15.
PLoS One ; 6(7): e22204, 2011.
Article in English | MEDLINE | ID: mdl-21765953

ABSTRACT

BACKGROUND: Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance. METHODS: We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2-infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1. RESULTS: No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein. CONCLUSION: Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at "secondary" HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2-infected patients.


Subject(s)
Genetic Variation/drug effects , HIV Integrase Inhibitors/pharmacology , HIV Integrase/genetics , HIV-2/enzymology , HIV-2/genetics , Adult , Base Sequence , Drug Resistance, Viral/drug effects , Drug Resistance, Viral/genetics , Female , HIV-2/drug effects , Humans , Male , Middle Aged , Molecular Sequence Data , Phylogeny , Senegal , Young Adult
16.
Cancer Epidemiol Biomarkers Prev ; 19(7): 1682-5, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20570905

ABSTRACT

BACKGROUND: Little is known about detection of genital human papilloma virus (HPV) types in women's fingertips. The study objectives were to determine the presence of genital HPV types in fingertip samples and the agreement between fingertip and genital samples for detecting HPV. METHODS: At triannual visits, genital and fingertip samples were collected from female university students and tested for 37 HPV genotypes by PCR-based assay. Type-specific concordance between paired fingertip and genital samples was evaluated using kappa statistics for percent positive agreement (kappa+). Paired samples with type-specific concordant fingertip and genital results were selected for variant characterization. RESULTS: A total of 357 fingertip samples were collected from 128 women. HPV prevalence in fingertip samples was 14.3%. Although percent positive agreement between fingertips and genitals for detecting type-specific HPV was low (17.8%; kappa+ = 0.17; 95% confidence interval, 0.10-0.25), 60.4% of type-specific HPV detected in the fingertips was detected in a concurrent genital sample. All but one of 28 paired concordant samples were positive for the same type-specific variant in the fingertip and genital sample. Redetection of HPV types at the subsequent visit was more common in genital samples (73.3%) than in fingertip samples (14.5%; P < 0.001). CONCLUSIONS: Detection of genital HPV types in the fingertips was not uncommon. Although impossible to distinguish between deposition of DNA from the genitals to the fingertips and true fingertip infection, the rarity of repeat detection in the fingertips suggests that deposition is more common. IMPACT: Finger-genital transmission is plausible but unlikely to be a significant source of genital HPV infection.


Subject(s)
Fingers/virology , Papillomaviridae/isolation & purification , Papillomavirus Infections/virology , Adolescent , Cervix Uteri/virology , Female , Humans , Papillomaviridae/classification , Papillomaviridae/genetics , Sexual Behavior , Students , Universities , Vaginal Smears/methods , Young Adult
17.
Cancer Epidemiol Biomarkers Prev ; 18(9): 2507-12, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19690188

ABSTRACT

BACKGROUND: Infection with multiple human papillomavirus (HPV) types is common. However, it is unknown whether viral DNA load is related to the coexistence of other types. METHODS: Study subjects were 802 and 303 women who were positive for HPV16 and HPV18, respectively, at enrollment into the Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study. HPV16 and HPV18 E7 copies per nanogram of cellular DNA in cervical swab samples were measured by real-time PCR in triplicate. RESULTS: Concurrent coinfection was common in this population of women with minor cervical lesions; multiple HPV types were detected in 573 (71.4%) of 802 HPV16-positive women and 227 (74.9%) of 303 HPV18-positive women. The adjusted odds ratio associating coinfection with per 1 log unit increase in HPV16 DNA load was 0.78 (95% confidence interval, 0.68-0.89); it was 0.64 (95% confidence interval, 0.52-0.79) for a similar analysis of HPV18 DNA load. Women with, compared with without, coinfection of A9 species types possessed a significantly lower HPV16 DNA load (P < 0.001), whereas women with, compared with without, coinfection of A7 species types possessed a significantly lower HPV18 DNA load (P = 0.001). A trend of decrease in HPV16 DNA load with increasing number of the coexisting non-HPV16 A9 species types was statistically significant (P(trend) = 0.001). CONCLUSION: Coinfection with other types was associated with lower HPV16 and HPV18 DNA load. The extent of reduction was correlated to phylogenetic distance of the coexisting types to HPV16 and HPV18, respectively.


Subject(s)
DNA, Viral/blood , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Papillomavirus Infections/virology , Uterine Cervical Diseases/virology , Early Detection of Cancer , Female , Human papillomavirus 16/isolation & purification , Human papillomavirus 18/isolation & purification , Humans , Papillomavirus Infections/epidemiology , United States/epidemiology , Uterine Cervical Diseases/epidemiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/virology , Viral Load , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/virology
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