Long-term increases in lymphocytes and platelets in human T-lymphotropic virus type II infection.

Human T-lymphotropic viruses types I and II (HTLV-I and HTLV-II) cause chronic infections of T lymphocytes that may lead to leukemia and myelopathy. However, their long-term effects on blood counts and hematopoiesis are poorly understood. We followed 151 HTLV-I-seropositive, 387 HTLV-II-seropositive, and 799 HTLV-seronegative former blood donors from 5 U.S. blood centers for a median of 14.0 years. Complete blood counts were performed every 2 years. Multivariable repeated measures analyses were conducted to evaluate the independent effect of HTLV infection and potential confounders on 9 hematologic measurements. Participants with HTLV-II had significant (P < .05) increases in their adjusted lymphocyte counts (+126 cells/mm(3); approximately +7%), hemoglobin (+2 g/L [+0.2 g/dL]) and mean corpuscular volume (MCV; 1.0 fL) compared with seronegative participants. Participants with HTLV-I and HTLV-II had higher adjusted platelet counts (+16 544 and +21 657 cells/mm(3); P < .05) than seronegatives. Among all participants, time led to decreases in platelet count and lymphocyte counts, and to increases in MCV and monocytes. Sex, race, smoking, and alcohol consumption all had significant effects on blood counts. The HTLV-II effect on lymphocytes is novel and may be related to viral transactivation or immune response. HTLV-I and HTLV-II associations with higher platelet counts suggest viral effects on hematopoietic growth factors or cytokines.

Prevalence of Trichomonas vaginalis infection among young reproductive age women in India: implications for treatment and prevention.

BACKGROUND: Trichomonas vaginalis infection is the most common curable sexually transmissible infection (STI) worldwide. The present study describes the burden and correlates of T. vaginalis infection among young reproductive age women in Mysore, India. METHODS: Between November 2005 and March 2006, sexually active women aged 15-30 years were recruited from low-income peri-urban and rural neighbourhoods of Mysore, India. Participants were interviewed and offered a physical examination and testing for T. vaginalis, bacterial vaginosis, vaginal candidiasis, Neisseria gonorrheoea and herpes simplex virus type-2 antibodies. RESULTS: Of the 898 participating women, 76 had a T. vaginalis infection (8.5%, 95% confidence interval [95% CI]: 6.7-10.5%). Nearly all (98%) participants were married and most reported their spouse as their main sex partner. The mean age at marriage was 16.9 years (s.d. 2.9 years) and two-thirds of the sample reported having first sexual intercourse before the age of 19 years. Risk factors independently associated with T. vaginalis infection included early age at first intercourse (adjusted odds ratio [OR] 2.09; 95% CI: 1.09-4.00), concurrent bacterial vaginosis (OR 8.21; 95% CI: 4.30-15.66), vaginal candidiasis (OR 2.40; 95% CI: 1.48-3.89) and herpes simplex virus type-2 infection (OR 3.44; 95% CI: 1.97-6.02). CONCLUSION: The burden of T. vaginalis infection at 8.5% is relatively high among a community sample of young reproductive aged women. Because this infection increases the risk of HIV transmission and is associated with adverse pregnancy outcomes, there is a need for increased screening and treatment of this easily curable sexually transmissible infection in India.

Standardized assessment of NAb responses elicited in rhesus monkeys immunized with single- or multi-clade HIV-1 envelope immunogens.

The genetic diversity of HIV-1 envelope glycoproteins (Env) remains a major obstacle to the development of an antibody-based AIDS vaccine. The present studies examine the breadth and magnitude of neutralizing antibody (NAb) responses in rhesus monkeys after immunization with DNA prime-recombinant adenovirus (rAd) boost vaccines encoding either single or multiple genetically distant Env immunogens, and subsequently challenged with a pathogenic simian-human immunodeficiency virus (SHIV-89.6P). Using a standardized multi-tier panel of reference Env pseudoviruses for NAb assessment, we show that monkeys immunized with a mixture of Env immunogens (clades A, B, and C) exhibited a greater breadth of NAb activity against neutralization-sensitive Tier 1 viruses following both vaccination and challenge compared to monkeys immunized with a single Env immunogen (clade B or C). However, all groups of Env-vaccinated monkeys demonstrated only limited neutralizing activity against Tier 2 pseudoviruses, which are more characteristic of the neutralization sensitivity of circulating HIV-1. Notably, the development of a post-challenge NAb response against SHIV-89.6P was similar in monkeys receiving either clade B, clade C, or clade A+B+C Env immunogens, suggesting cross-clade priming of NAb responses. In addition, vaccines encoding Env immunogens heterologous to SHIV-89.6P primed for a rapid anamnestic NAb response following infection compared to vaccines lacking an Env component. These results show that DNA/rAd immunization with multiple diverse Env immunogens is a viable approach for enhancing the breadth of NAb responses against HIV-1, and suggest that Env immunogens can prime for anamnestic NAb responses against a heterologous challenge virus.

Fluctuations of functionally distinct CD8+ T-cell clonotypes demonstrate flexibility of the HIV-specific TCR repertoire.

T-cell receptor (TCR) diversity of virus-specific CD8+ T cells likely helps prevent escape mutations in chronic viral infections. To understand the dynamics of the virus-specific T cells in more detail, we followed the evolution of the TCR repertoire specific for a dominant HLA-B*08-restricted epitope in Nef (FLKEKGGL) in a cohort of subjects infected with HIV. Epitope-specific CD8+ T cells used structurally diverse TCR repertoires, with different TCRbeta variable regions and with high amino acid diversity within antigen recognition sites. In a longitudinal study, distinct Vbeta populations within the HIV-specific TCR repertoire expanded simultaneously with changes in plasma viremia, whereas other Vbeta populations remained stable or even decreased. Despite antigenic variation in some subjects, all subjects had the consensus sequence present during the study period. Functional analysis of distinct Vbeta populations revealed differences in HIV-specific IFN-gamma secretion ex vivo as well as differences in tetramer binding, indicating functional heterogeneity among these populations. This contrasts with findings in a subject on antiretroviral therapy with suppression of viremia to less than 50 copies/mL, where we observed long-term persistence of a single clonotype. Our findings illustrate the flexibility of a heterogeneous HIV-1-specific CD8+ TCR repertoire in subjects with partial control of viremia.