The predictive value of cytologic testing in women with the human immunodeficiency virus who have low-grade squamous cervical lesions: A substudy of a randomized, phase III chemoprevention trial

2003 ◽  
Vol 188 (4) ◽  
pp. 896-900 ◽  
Author(s):  
William R. Robinson ◽  
Mindy B. Luck ◽  
Michelle A. Kendall ◽  
Teresa M. Darragh
2019 ◽  
Vol 69 (12) ◽  
pp. 2185-2192 ◽  
Author(s):  
Pompeyo Viciana ◽  
Yusnelkis Milanés-Guisado ◽  
María Fontillón ◽  
Ana Domínguez Castaño ◽  
César Sotomayor ◽  
...  

Abstract Background Screening methods for anal squamous intraepithelial lesions (SILs) are suboptimal. We aimed to determine the diagnostic performance of a composite endpoint comprising anal liquid-based cytology (aLBC) and high-risk human papillomavirus (HR-HPV) testing to predict histological high-grade SILs (hHSILs). Methods From the SeVIHanal cohort, human immunodeficiency virus (HIV)–infected men who have sex with men (MSM) who had an aLBC with concomitant HR-HPV testing were included. hHSILs were determined by high-resolution anoscopy (HRA)–guided biopsy. Results A total of 705 visits obtained from 426 patients were included. The prevalence of HR-HPV among aLBC results were 51.9% (133/215) normal, 87.9% (20/232) low-grade SILs (LSILs), and 90.9% (149/164) high-grade SILs; P (linear association) < .001. Low prevalence of hHSILs was only observed for the composite aLBC/HR-HPV testing endpoint “normal/noHR-HPV” (10%) and “LSIL/noHR-HPV” (4%). The prognostic values (95% confidence interval) for HR-HPV to predict hHSILs in normal cytology were positive predictive value (PPV), 29.3% (25.6%–33.3%); negative predictive value (NPV), 90.2% (82.8%–94.7%); sensitivity, 83% (69.2%–92.4%); and specificity, 44.1% (36.4%–51.9%). Corresponding figures for cytologic LSILs were PPV, 39.2% (37.4%–41.1%); NPV, 96.4% (78.9%–99.5%); sensitivity, 98.8% (93.3%–99.9%); and specificity, 17.9% (12.1%–24.9%). A positive interaction and a synergistic effect for the composite endpoint were observed (relative excess risk = 1.50, attributable proportion of histological results to interaction = 0.17, synergy index = 1.24). Conclusions HRA should not be indicated in the setting of LSILs/noHR-HPV following aLBC-based screening. In contrast, HIV-infected MSM with normal aLBC/HR-HPV infection should be considered for HRA. Clinical Trials Registration NCT03713229.


2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Hanna B. Scinto ◽  
Sandeep Gupta ◽  
Swati Thorat ◽  
Muhammad M. Mukhtar ◽  
Anthony Griffiths ◽  
...  

ABSTRACTThe phase III RV144 human immunodeficiency virus (HIV) vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing the HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clade A/E (CRF01_AE) predominate; in such viruses,envoriginates from clade E (HIV-E). We constructed a simian-human immunodeficiency virus (SHIV) chimera carryingenvisolated from an RV144 placebo recipient in the SHIV-1157ipd3N4 backbone. The latter contains long terminal repeats (LTRs) with duplicated NF-κB sites, thus resembling HIV LTRs. We devised a novel strategy to adapt the parental infectious molecular clone (IMC), R5 SHIV-E1, to rhesus macaques: the simultaneous depletion of B and CD8+cells followed by the intramuscular inoculation of proviral DNA and repeated administrations of cell-free virus. High-level viremia and CD4+T-cell depletion ensued. Passage 3 virus unexpectedly caused acute, irreversible CD4+T-cell loss; the partially adapted SHIV had become dual tropic. Virus and IMCs with exclusive R5 tropism were reisolated from earlier passages, combined, and used to complete adaptation through additional macaques. The final isolate, SHIV-E1p5, remained solely R5 tropic. It had a tier 2 neutralization phenotype, was mucosally transmissible, and was pathogenic. Deep sequencing revealed 99% Env amino acid sequence conservation; X4-only and dual-tropic strains had evolved independently from an early branch of parental SHIV-E1. To conclude, our primate model data reveal that SHIV-E1p5 recapitulates important aspects of HIV transmission and pathobiology in humans.IMPORTANCEUnderstanding the protective principles that lead to a safe, effective vaccine against HIV in nonhuman primate (NHP) models requires test viruses that allow the evaluation of anti-HIV envelope responses. Reduced HIV acquisition risk in RV144 has been linked to nonneutralizing IgG antibodies with a range of effector activities. Definitive experiments to decipher the mechanisms of the partial protection observed in RV144 require passive-immunization studies in NHPs with a relevant test virus. We have generated such a virus by insertingenvfrom an RV144 placebo recipient into a SHIV backbone with HIV-like LTRs. The final SHIV-E1p5 isolate, grown in rhesus monkey peripheral blood mononuclear cells, was mucosally transmissible and pathogenic. Earlier SHIV-E passages showed a coreceptor switch, again mimicking HIV biology in humans. Thus, our series of SHIV-E strains mirrors HIV transmission and disease progression in humans. SHIV-E1p5 represents a biologically relevant tool to assess prevention strategies.


2019 ◽  
Vol 69 (9) ◽  
pp. 1555-1565 ◽  
Author(s):  
Pierre Debeaudrap ◽  
Joelle Sobngwi ◽  
Pierre-Marie Tebeu ◽  
Gary M Clifford

Abstract Background Screening and treating premalignant cervical lesions (cervical intraepithelial neoplasia 2+ [CIN2+]) is an effective way to prevent cervical cancer, and recommendations exist for the monitoring of treatment success. Yet, there is no specific recommendation for human immunodeficiency virus (HIV)-infected women, who are at a known, increased risk of cervical cancer. Methods A systematic review was performed by searching MEDLINE, EMBASE, and Web of Science for studies published from January 1980 through May 2018. Eligible studies described the prevalence of histologically- and/or cytologically-defined lesions in HIV-infected women at least 6 months post-treatment. The primary endpoint was treatment failure, defined as the presence of residual and/or recurrent high-grade CIN2+/high-grade squamous intraepithelial lesions post-treatment. The pooled prevalence in HIV-infected women and the odds ratios (ORs) for HIV-infected compared to HIV-uninfected women were estimated using random-effects models. Results Among 40 eligible studies, the pooled prevalence of treatment failure in HIV-infected women was 21.4% (95% confidence interval [CI] 15.8–27.0). There was no significant difference in the treatment failure prevalence for cryotherapy (13.9%, 95% CI 6.1–21.6) versus loop electrosurgical excision procedure (13.8%, 95% CI 8.9–18.7; P = .9), but the treatment failure prevalence was significantly higher in women with positive (47.2%, 95% CI 22.0–74.0) than with negative (19.4%, 95% CI 11.8–30.2) excision margin (OR 3.4, 95% CI 1.5–7.7). Treatment failure was significantly increased in HIV-infected versus HIV-uninfected women, both overall (OR 2.7, 95% CI 2.0–3.5) and in all sub-group analyses. Conclusions There is strong evidence for an increased risk of treatment failure in HIV-infected women, in comparison to their HIV-negative counterparts. The only significant predictor of treatment failure in HIV-infected women was a positive margin status, but further data is needed on long-term outcomes after ablative treatment in HIV-infected women.


2018 ◽  
Vol 28 (7) ◽  
pp. 1432-1437 ◽  
Author(s):  
Leon Cornelius Snyman ◽  
Emma P. Bryant ◽  
Elize I. Wethmar ◽  
Tom de Greve ◽  
Florette Reyneke ◽  
...  

ObjectivesCervical cancer is common in resource-poor settings with high prevalence of tuberculosis, pelvic inflammatory disease, and human immunodeficiency virus (HIV) infection. There are no data regarding the sentinel lymph node (SLN) algorithm in these high-risk cancer populations. Our objectives were to establish the sensitivity, specificity, positive predictive value, and negative predictive value of the SLN algorithm in cervical cancer and to compare the detection rate of indocyanine green (ICG) versus blue dye versus technetium Tc 99m nanocolloid (99mTc).MethodsThis prospective study was conducted at the University of Pretoria. 99mTc-nanocolloid tracer, ICG dye, and methylene blue (MB) were used to detect SLNs. Pathological ultrastaging was performed on hematoxylin-eosin– negative nodes.ResultsResults of 72 women were analyzed. The mean age was 47.2 years, 5.5% had a history of tuberculosis, 18.1% had pelvic inflammatory disease, and 65.3% were HIV positive. The SLN detection rate was 65.3%. Detection rate of MB was 56.9%; 99mTc, 69.4%; ICG, 87.5%; and the combination of MB and 99mTc, 91.7%. Pelvic nodal metastases occurred in 26.4%. The sensitivity, specificity, negative predictive value, and positive predictive value of SLN biopsy were 85.7%, 100%, 100%, and 98.33%, respectively. The false-negative rate was 14.3%, and it was 0% if the algorithm was applied.ConclusionsThe SLN algorithm is a feasible option for use in cervical cancer women with a high prevalence of HIV infection. The detection rate is generally lower, but in select subgroups of women, it was comparable to that reported elsewhere. This is the first report of the use of SLN biopsy in a substantial group of HIV-infected women.


2003 ◽  
Vol 187 (1) ◽  
pp. 38-46 ◽  
Author(s):  
Isabelle Pellegrin ◽  
Anne Caumont ◽  
Isabelle Garrigue ◽  
Patrick Merel ◽  
Marie‐Hélène Schrive ◽  
...  

2001 ◽  
Vol 8 (2) ◽  
pp. 346-348 ◽  
Author(s):  
Bhavna H. Chohan ◽  
Ludo Lavreys ◽  
Kishorchandra N. Mandaliya ◽  
Joan K. Kreiss ◽  
Job J. Bwayo ◽  
...  

ABSTRACT This study was performed to evaluate the performance of a saliva collection device (OmniSal) and an enzyme-linked immunoassay (EIA) designed for use on serum samples (Detect HIV1/2) to detect human immunodeficiency virus type 1 (HIV-1) antibodies in the saliva of high-risk women in Mombasa, Kenya. The results of the saliva assay were compared to a “gold standard” of a double-EIA testing algorithm performed on serum. Individuals were considered HIV-1 seropositive if their serum tested positive for antibodies to HIV-1 by two different EIAs. The commercial serum-based EIA was modified to test the saliva samples by altering the dilution and lowering the cutoff point of the assay. Using the saliva sample, the EIA correctly identified 102 of the 103 seropositive individuals, yielding a sensitivity of 99% (95% confidence interval [CI], 94 to 100%), and 96 of the 96 seronegative individuals, yielding a specificity of 100% (95% CI, 95 to 100%). In this high-risk population, the positive predictive value of the assay was 100% and the negative predictive value was 99%. We conclude that HIV-1 antibody testing of saliva samples collected with this device and tested by this EIA is of sufficient sensitivity and specificity to make this protocol useful in epidemiological studies.


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