[Show abstract][Hide abstract] ABSTRACT: HIV persists in a reservoir of latently infected CD4(+) T cells in individuals treated with highly active antiretroviral therapy (HAART). Here we identify central memory (T(CM)) and transitional memory (T(TM)) CD4(+) T cells as the major cellular reservoirs for HIV and find that viral persistence is ensured by two different mechanisms. HIV primarily persists in T(CM) cells in subjects showing reconstitution of the CD4(+) compartment upon HAART. This reservoir is maintained through T cell survival and low-level antigen-driven proliferation and is slowly depleted with time. In contrast, proviral DNA is preferentially detected in T(TM) cells from aviremic individuals with low CD4(+) counts and higher amounts of interleukin-7-mediated homeostatic proliferation, a mechanism that ensures the persistence of these cells. Our results suggest that viral eradication might be achieved through the combined use of strategic interventions targeting viral replication and, as in cancer, drugs that interfere with the self renewal and persistence of proliferating memory T cells.
Nature medicine 07/2009; 15(8):893-900. DOI:10.1038/nm.1972 · 27.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV) causes anal intraepithelial neoplasia (AIN) in HIV-seropositive men. The detection of HPV genotypes in anal biopsies and swabs was compared.
HPV DNA was detected in anal swabs and biopsies obtained concurrently from 154 HIV-seropositive men [31 without AIN, 60 low-grade AIN (AIN-1), 62 high-grade AIN (AIN-2,3), and 1 indeterminate AIN] under or eligible to highly active antiretroviral therapy.
HPV DNA was detected in 24.2% of normal biopsies compared with 93.5% with AIN-2,3 (P < 0.001) and 88.3% with AIN-1 (P < 0.001). The proportion of biopsies containing multiple genotypes was greater in AIN-1 (n = 21, 35.0%; P = 0.002) and AIN-2,3 (n = 38, 58%; P < 0.001) than in normal biopsies (n = 2, 6.5%). The most frequent genotypes in order of frequency were in AIN-2,3 biopsies HPV-16, 18, 58, and 45 and were in AIN-1 biopsies HPV-6, 11, 16, and 39. Controlling for age, CD4 count, and smoking, the presence of high-risk HPV DNA in biopsies [odds ratio (OR) = 50.8, 95% confidence interval (CI): 13.0 to 199.5] but not in swabs (OR = 2.0, 95% CI: 0.6 to 7.0) was associated with AIN-2,3.
AIN-2,3 was associated with high-risk HPV infection detected in biopsies but not in swabs in men under or starting highly active antiretroviral therapy, possibly due to the presence of HPV foci outside of the neoplastic lesion.
[Show abstract][Hide abstract] ABSTRACT: A novel real-time PCR assay for detection of human papillomavirus type 52 (HPV-52) DNA (RT-52) was evaluated on 265 anogenital samples. RT-52 had a sensitivity of 98.4% and a specificity of 100% compared to conventional HPV-52 typing assays, including hybridization of PGMY products with an HPV-52-specific probe and PCR sequencing of HPV-52 E6.
[Show abstract][Hide abstract] ABSTRACT: The Roche PGMY primer-based research prototype line blot assay (PGMY-LB) is a convenient tool in epidemiological studies for the detection and typing of human papillomavirus (HPV) DNA. This assay has been optimized and is being commercialized as the Linear Array HPV genotyping test (LA-HPV). We assessed the agreement between LA-HPV and PGMY-LB for detection and typing of 37 HPV genotypes in 528 anogenital samples (236 anal, 146 physician-collected cervical, and 146 self-collected cervicovaginal swabs) obtained from human immunodeficiency virus-seropositive individuals (236 men and 146 women). HPV DNA was detected in 433 (82.0%) and 458 (86.7%) samples with PGMY-LB and LA-HPV (P = 0.047), respectively, for an excellent agreement of 93.8% (kappa = 0.76). Of the 17,094 HPV typing results, 16,562 (1,743 positive and 14,819 negative results) were concordant between tests (agreement = 96.9%; kappa = 0.76). The mean agreement between tests for each type was 96.4% +/- 2.4% (95% confidence interval [CI], 95.6% to 97.2%; range, 86% to 100%), for an excellent mean kappa value of 0.85 +/- 0.10 (95% CI, 0.82 to 0.87). However, detection rates for most HPV types were greater with LA-HPV. The mean number of types per sample detected by LA-HPV (4.2 +/- 3.4; 95% CI, 3.9 to 4.5; median, 3.0) was greater than that for PGMY-LB (3.4 +/- 3.0; 95% CI, 3.1 to 3.6; median, 2.0) (P < 0.001). The number of types detected in excess by LA-HPV in anal samples correlated with the number of types per sample (r = 0.49 +/- 0.06; P = 0.001) but not with patient age (r = 0.03 +/- 0.06; P = 0.57), CD4 cell counts (r = 0.06 +/- 0.06; P = 0.13), or the grade of anal disease (r = -0.11 +/- 0.06; P = 0.07). LA-HPV compared favorably with PGMY-LB but yielded higher detection rates for newer and well-known HPV types.
[Show abstract][Hide abstract] ABSTRACT: The presence of human papillomavirus (HPV) DNA in esophageal brushings from human immunodeficiency virus (HIV)-seropositive hosts was investigated in a cross-sectional study. Oral and esophageal brushings from individuals scheduled for esophagogastroscopy (53 HIV-positive and 61 age-matched HIV-negative patients) were tested for the presence of HPV DNA by a consensus L1 polymerase chain reaction assay. HPV DNA was detected in esophageal brushings of 9 (17%) of the 53 HIV-seropositive patients and 0 of the 61 HIV-negative individuals. HPV-16 DNA was the most frequently detected. No proliferative mucosal lesion was noted in individuals with HPV-positive esophageal brushings. Cytological smears were done for 6 of the 9 patients with HPV-positive esophageal brushings, and epithelial atypia was recorded for 1. HIV infection and a history of genital herpes were strong independent predictors of HPV, suggesting that HPV is transmitted sexually in the esophagus.
[Show abstract][Hide abstract] ABSTRACT: To investigate in a cross-sectional study the determinants of oral human papillomavirus infection in 287 individuals who are sexually active.
To assess prevalence as well as risk factors for oral human papillomavirus infection.
One hundred seventy-eight human immunodeficiency virus-seropositive (158 men and 20 women) and 109 human immunodeficiency virus-negative (73 men and 36 women) individuals were recruited consecutively from sexually transmitted disease-human immunodeficiency virus clinics and gastrointestinal endoscopy clinics. Oral brushings were tested with the L1 consensus polymerase chain reaction assay for human papillomavirus detection.
Human papillomavirus DNA was detected in 32 (11.2%) of 287 individuals. Associated with oral human papillomavirus infection on univariate analyses were human immunodeficiency virus infection (odds ratio, 6.9; 95% confidence interval, 2.0-23.2), homosexuality (odds ratio, 3.7; 95% confidence interval, 1.5-9.4), unprotected oral sex (odds ratio, 5.5; 95% confidence interval, 1.6-18.4), syphilis (odds ratio, 2.5; 95% confidence interval, 1.1-6.3), gonorrhea (odds ratio, 4.2; 95% confidence interval, 1.9-9.1), Chlamydia trachomatis (odds ratio, 4.4; 95% confidence interval, 1.8-10.6), and genital herpes (odds ratio, 2.9; 95% confidence interval, 1.3-6.5). Human immunodeficiency virus infection and C. trachomatis were independently predictive of human papillomavirus infection in multivariate stepwise logistic regression.
Sex Transm Dis 02/1997; 24(1):23-31. DOI:10.1097/00007435-199701000-00006 · 2.84 Impact Factor