HIV-1/HSV-2 Co-Infected Adults in Early HIV-1 Infection Have Elevated CD4+ T Cell Counts

Introduction. HIV-1 is often acquired in the presence of pre-existing co-infections, such as Herpes Simplex Virus 2 (HSV-2). We examined the impact of HSV-2 status at the time of HIV-1 acquisition for its impact on subsequent clinical course, and total CD4+ T cell phenotypes. Methods. We assessed the relationship of HSV-1/HSV-2 co-infection status on CD4+ T cell counts and HIV-1 RNA levels over time prior in a cohort of 186 treatment naive adults identified during early HIV-1 infection. We assessed the activation and differentiation state of total CD4+ T cells at study entry by HSV-2 status. Results. of 186 recently HIV-1 infected persons, 101 (54%) were sero-positive for HSV-2. There was no difference in initial CD8+ T cell count, or differences between the groups for age, gender, or race based on HSV-2 status. Persons with HIV-1/HSV-2 co-infection sustained higher CD4+ T cell counts over time (+69 cells/ul greater (SD = 33.7, p = 0.04) than those with HIV-1 infection alone (Figure 1), after adjustment for HIV-1 RNA levels (-57 cells per 1 log(10) higher HIV-1 RNA, p<0.0001). We did not observe a relationship between HSV-2 infection status with plasma HIV-1 RNA levels over time. HSV-2 acquistion after HIV-1 acquisition had no impact on CD4+ count or viral load. We did not detect differences in CD4+ T cell activation or differentiation state by HSV-2+ status. Discussion. We observed no effect of HSV-2 status on viral load. However, we did observe that treatment naive, recently HIV-1 infected adults co-infected with HSV-2+ at the time of HIV-1 acquisition had higher CD4+ T cell counts over time. If verified in other cohorts, this result poses a striking paradox, and its public health implications are not immediately clear.Brazilian Program for STD and AIDS, Ministry of HealthSão Paulo City Health DepartmentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)NIAID/NIHJohn E. Fogarty International CenterAIDS Research Institute of the AIDS Biology Program at UCSFCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Brazilian Ministry of EducationUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilUniv Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USAUniv Calif San Francisco, Dept Expt Med, San Francisco, CA USASao Paula City Hlth Syst, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilBrazilian Program for STD and AIDS, Ministry of Health: 914/BRA/3014 UNESCO/KallasSão Paulo City Health Department: 2004-0.168.922-7/KallasFAPESP: 04/15856-9/KallasNIAID/NIH: AI066917/BarbourNIAID/NIH: AI064520/NixonJohn E. Fogarty International Center: D43 TW00003Web of Scienc

GB virus type C infection modulates T-cell activation independently of HIV-1 viral load

Background: Many clinical studies have suggested a beneficial effect of GB virus type C (GBV-C) on the course of HIV-1 infection, but the mechanisms involved in such amelioration are not clear. As recent evidence has implicated cellular activation in HIV-1 pathogenesis, we investigated the effect of GBV-C viremia on T-cell activation in early HIV-1 infection. Methods: Forty-eight recently infected HIV-1 patients (23 GBV-C viremic) were evaluated for T-cell counts, expanded immunophenotyping GBV-C RNA detection, and HIV-1 viral load. Nonparametric univariate and multivariate analyses were carried out to identify variables associated with cellular activation, including GBV-C status, HIV-1 viral load, T lymphocyte counts, and CD38 and chemokine (C-C motif) receptor 5 (CCR5) surface expression. Finding: We not only confirmed the positive correlation between HIV-1 viral load and the percentage of T cells positive for CD38(+)CD8(+) but also observed that GBV-C viremic patients had a lower percentage of T cells positive for CD38(+)CD4(+), CD38(+)CD8(+), CCR5(+)CD4(+), and CCR5(+)CD8(+) compared with HIV-1-infected patients who were not GBV-C viremic. In regression models, GBV-C RNA(+) status was associated with a reduction in the CD38 on CD4(+) or CD8(+) T cells and CCR5(+) on CD8(+) T cells, independent of the HIV-1 viral load or CD4(+) and CD8(+) T-cell counts. These results were also supported by the lower expression of CD69 and CD25 in GBV-C viremic patients. Interpretation: The association between GBV-C replication and lower T-cell activation may be a key mechanism involved in the protection conferred by this virus against HIV-1 disease progression to immunodeficiency in HIV-1-infected patients. (C) 2009 Wolters Kluwer Health | Lippincott Williams & WilkinsBrazilian Program for STD and AIDS, Ministry of Health[914/BRA/3014-UNESCO/Kallas]Sao Paulo City Health Department[2004-0.168.922-7/Kallas]FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[04/15856-9/Diaz]FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[05/01072-9/Levi)]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazilian Ministry of Educatio

Establishment of the serologic testing algorithm for recent human immunodeficiency virus (HIV) seroconversion (STARHS) strategy in the city of São Paulo, Brazil

Several strategies aim at characterizing the AIDS epidemic in different parts of the world. Among these, the identification of recent HIV-1 infections using the recently described serologic testing algorithm for recent human immunodeficiency virus (HIV) seroconversion (STARHS) strategy was employed in four testing sites of the City of São Paulo Public Health Department (CSPPHD). Those identified as recently infected were invited to participate in a prospective clinical and laboratory evaluation study. We describe the establishment of the patient identification network and the success in enrolling the participants, as well as their clinical and laboratory characteristics. From May to December 2002, 6,443 persons were tested for HIV in the four participating sites, of whom 384 (5.96%) tested HIV-1 positive; 43 (11.2%) of them were identified as recently infected. Twenty-two were successfully enrolled in the follow-up study, but three of them did not meet clinical and/or laboratory criteria for recent HIV-1 infection. After these exclusions, the laboratory findings revealed a median CD4+ T lymphocyte count of 585 cells/muL (inter-quartile range 25-75% [IQR], 372-754), a CD8+ T lymphocyte count of 886 cells/muL (IQR, 553-1098), a viral load of 11,000 HIV-RNA copies/mL (IQR, 3,650-78,150), log10 of 4.04 (IQR 3.56-4.88). The identification of recent HIV infections is an extremely valuable way to evaluate the spread of the virus in a given population, especially when cohort studies, considered the gold standard method to evaluate incidence, are not available. This work demonstrated that establishing a network to identify such patients is a feasible task, even considering the difficulties in a large, resource-limited country or city

Clinical and Demographic Characteristics of the Study Cohort At Study Entry.

*<p>Anti Hepatitis B Core Antibody.</p

HSV-2 acquisition after HIV-1 acquisition is not associated with subsequent differences in CD4+ T cell counts or HIV-1 viral load.

<p>The open blue diamonds represent the CD4+ T cell counts, and the open red dots represent HIV-1 viral load, over time for persons testing positive for HSV-2 at 1 year after study enrollment. The solid blue diamonds represent the CD4+ T cell counts, and the solid red dots HIV-1 viral load, for those HSV-2 negative at 1 year after study enrollment. Forty-seven of the 85 persons who tested HSV-2 negative at study entry were re-tested. Observations were right censored at the time persons initiated anti-retroviral therapy, which was initiated at approximately a CD4+ T cell count of 350 cells/µL.</p

Higher absolute CD4+ T cell counts in HSV-2+/HIV-1+ subjects independent of HIV-1 viral load.

<p>The open blue diamonds represent the CD4+ T cell counts, and the open red dots represent HIV-1 viral load over time for persons co-infected with HSV-2 at the time of diagnosis with an early HIV-1 infection. The solid blue diamonds represent the CD4+ T cell counts, and the solid red dots HIV-1 viral load, for those HSV-2 negative at the time of early HIV-1 infection. Observations were right censored at the time anti-retroviral therapy was initiated, which occurred at approximately a CD4+ T cell count of 350 cells/µL.</p