Cervical shedding of human T cell lymphotropic virus type I is associated with cervicitis

Human T cell lymphotropic virus type I (HTLV-I) is sexually transmitted. The purpose of this study was to determine the prevalence and risk factors for cervical shedding of HTLV-I DNA among Peruvian sex workers. HTLV tax DNA was detected in cervical specimens from 43 (68%) of 63 HTLV-I-infected sex workers and in samples obtained during 113 (52%) of 216 clinic visits between 1993 and 1997. Detection of HTLV DNA was associated with the presence of > or =30 polymorphonuclear cells (PMNs) within cervical mucus per 100x microscopic field (odds ratio [OR], 4.3, 95% confidence interval [CI], 1.8-10.1) and with the presence of cervical secretions (OR, 2.0; 95% CI 1.2-3.4). Hormonal contraceptive use (OR 1.7; 95% CI, 0.8-3.6) and concomitant cervical infection by Chlamydia trachomatis (OR, 1.5; 95% CI, 0.3-4.3) or Neisseria gonorrhoeae (OR, 1.1; 95% CI, 0.6-3.7) were not significantly associated with HTLV-I shedding. Our results suggest that cervicitis may increase cervical HTLV-I shedding and the sexual transmission of this virus.     

Acceptability of a Dapivirine/Placebo Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-026)

AIDS and Behavior - This study describes the acceptability of a rectal microbicide gel formulation using dapivirine (DPV) among men and women from two countries (United States and Thailand)...     

Characterization of a B-cell immunodominant epitope of human T-lymphotropic virus type 1 (HTLV-I) envelope gp46.

The immune response elicited by a synthetic peptide derived from an immunodominant external envelope region (Env-5, amino acids 242-257) of human T-lymphotropic virus type 1 (HTLV-I) was tested in a rabbit model of HTLV-I infection. The synthetic peptide elicited a strong antibody response to the HTLV-I envelope protein gp46; however, these antibodies failed to inhibit HTLV-I-mediated cell fusion. Immunized rabbits were not protected from HTLV-I infection as determined by seroconversion to viral core proteins by immunoblot, HTLV-I p24 antigen detection in lymphocyte cultures and polymerase chain reaction for the HTLV-I provirus in lymphocyte DNA. Env-5 peptide immunization failed to induce T-cell lymphocyte proliferative responses in rabbits, but induced antibody responses in T-cell deficient Balb c nu/nu mice suggesting that the antigenic determinant represented by the Env-5 peptide is primarily a B-cell epitope. These results further define an immunodominant epitope of the HTLV-I envelope protein and suggest that potential synthetic peptide vaccines against HTLV-I infection must contain multiple antigens that induce both humoral and cellular immune reactivity.     

Detection of infectious human immunodeficiency virus type 1 in female genital secretions by a short-term culture method

Infectious human immunodeficiency virus type 1 (HIV-1) is difficult to detect in female genital secretions by standard virus culture techniques. To improve detection of cell-free HIV-1 in female genital secretions, we adapted a short-term assay that uses the multinuclear-activation galactosidase indicator (MAGI) assay. When vaginal lavages from HIV-1-infected women were tested with the adapted MAGI assay, 25 (64%) of 39 lavages with detectable, cell-free HIV-1 RNA were shown to have infectious virus. No infectious virus was found in 10 vaginal lavages from HIV-1-infected women with undetectable vaginal viral loads. Significantly (P < 0.01) more lavages from HIV-1-infected women tested positive for infectious virus by the MAGI assay than by standard peripheral blood mononuclear cell (PBMC) coculture, which detected infectious virus in only 6 (17%) of 35 vaginal lavages. Lavages with viral loads of >10,000 copies per lavage yielded significantly (P < 0.01) more positive cultures than those with <10,000 copies by using the MAGI assay. Detection of infectious HIV-1 in vaginal lavages was not associated with the presence of genital tract infections or CD4(+)-T-cell counts. However, although the results were not significant (P = 0.08), the MAGI assay detected infectious virus from more vaginal lavages at a vaginal pH of >/=4.5 than at a pH of <4.5. These results indicate that the MAGI assay is more sensitive than PBMC culture methods for detecting infectious virus in female genital secretions. Accurate measurements of infectious virus in genital secretions will improve studies that evaluate sexual transmission of HIV-1.     

Detection of human T-lymphotropic virus (HTLV) tax sequences in New York City blood donors seronegative for HTLV types 1 and 2

A potential public health concern is the reported detection of the human T-lymphotropic virus (HTLV) tax gene in the lymphocytes of up to 11% of a low-risk group of New York City blood donors (NYBD). This study aimed to independently confirm the prevalence of HTLV tax sequences in 293 NYBD. All NYBD tested negative for antibodies to HTLV types 1 and 2 and HTLV Tax. HTLV tax sequences were not detected in the NYBD lymphocytes. These data demonstrate the lack of HTLV-1 tax in this group of NYBD at low risk for HTLV infection.     

Detection of Human T-Lymphotropic Virus (HTLV) tax Sequences in New York City Blood Donors Seronegative for HTLV Types 1 and 2

A potential public health concern is the reported detection of the human T-lymphotropic virus (HTLV) tax gene in the lymphocytes of up to 11% of a low-risk group of New York City blood donors (NYBD). This study aimed to independently confirm the prevalence of HTLV tax sequences in 293 NYBD. All NYBD tested negative for antibodies to HTLV types 1 and 2 and HTLV Tax. HTLV tax sequences were not detected in the NYBD lymphocytes. These data demonstrate the lack of HTLV-1 tax in this group of NYBD at low risk for HTLV infection.     

Targeted Delivery of PSC-RANTES for HIV-1 Prevention using Biodegradable Nanoparticles

Purpose  Nanoparticles formulated from the biodegradable co-polymer poly(lactic-co-glycolic acid) (PLGA), were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting for PSC-RANTES anti-HIV-1 activity. Materials and Methods  PSC-RANTES nanoparticles formulated via a double emulsion process and characterized in both in vitro and ex vivo systems to determine PSC-RANTES release rate, nanoparticle tissue permeation, and anti-HIV bioactivity. Results  Spherical, monodisperse (PDI = 0.098 ± 0.054) PSC-RANTES nanoparticles (d = 256.58 ± 19.57 nm) with an encapsulation efficiency of 82.23 ± 8.35% were manufactured. In vitro release studies demonstrated a controlled release profile of PSC-RANTES (71.48 ± 5.25% release). PSC-RANTES nanoparticle maintained comparable anti-HIV activity with unformulated PSC-RANTES in a HeLa cell-based system with an IC₅₀ of approximately 1pM. In an ex vivo cervical tissue model, PSC-RANTES nanoparticles displayed a fivefold increase in tissue uptake, enhanced tissue permeation, and significant localization at the basal layers of the epithelium over unformulated PSC-RANTES. Conclusions  These results indicate that PSC-RANTES can readily be encapsulated into a PLGA nanoparticle drug delivery system, retain its anti-HIV-1 activity, and deliver PSC-RANTES to the target tissue. This is crucial for the success of this drug candidate as a topical microbicide product.