Association of HLA Genotype With T-Cell Activation in Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus-Coinfected Women.

BACKGROUND: Global immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus . METHODS: We evaluated the relationship between 44 HLA class I and 28 class II alleles and percentages of activated CD8 (CD8+CD38+DR+) and CD4 (CD4+CD38+DR+) T cells in 586 women who were naive to highly active antiretroviral therapy. We used linear generalized estimating equation regression models, adjusting for race/ethnicity, age, HIV load, and hepatitis C virus infection and controlling for multiplicity using a false discovery rate threshold of 0.10. RESULTS: Ten HLA alleles were associated with CD8 and/or CD4 T-cell activation. Lower percentages of activated CD8 and/or CD4 T cells were associated with protective alleles B*57:03 (CD8 T cells, -6.6% [P = .002]; CD4 T cells, -2.7% [P = .007]), C*18:01 (CD8 T cells, -6.6%; P < .0008) and DRB1*13:01 (CD4 T cells, -2.7%; P < .0004), and higher percentages were found with B*18:01 (CD8 T cells, 6.2%; P < .0003), a detrimental allele. Other alleles/allele groups associated with activation included C*12:03, group DQA1*01:00, DQB1*03:01, DQB1*03:02, DQB1*06:02, and DQB1*06:03. CONCLUSION: These findings suggest that a person's HLA type may play a role in modulating T-cell activation independent of viral load and sheds light on the relationship between HLA, T-cell activation, immune control, and HIV pathogenesis.

Low Bioactive Vitamin D Is Associated with Pregnancy-Induced Hypertension in a Cohort of Pregnant HIV-Infected Women Sampled Over a 23-Year Period.

OBJECTIVE: To examine the association of vitamin D insufficiency and risk of pregnancy-induced hypertension (PIH) among human immunodeficiency virus (HIV)-infected pregnant women. STUDY DESIGN: This is a retrospective cohort study evaluating the impact of low maternal vitamin D levels on PIH and perinatal outcomes among HIV-infected pregnant women receiving care at an urban HIV center from 1991 to 2014. RESULTS: A total of 366 pregnant women were included, of which 11% developed PIH. Lower levels of 25-hydroxyvitamin D (25(OH)D) and bioactive 1,25-dihydroxyvitamin D (1,25(OH)2D) were associated with increased HIV disease activity. 25(OH)D levels were not significantly associated with the incidence of PIH. Higher 1,25(OH)2D levels were associated with reduced incidence of PIH in univariate (odds ratio, OR: 0.87 [95% confidence interval, CI: 0.79-0.95], p = 0.004) and multivariate (OR: 0.88 [95% CI: 0.80-0.97], p = 0.010) analyses. No association was found between 25(OH)D levels and other obstetric outcomes. Lower 1,25(OH)2D levels were associated with group B Streptococcus colonization (OR: 0.92 [95% CI: 0.86-0.99]) and low birth weight (LBW) (OR: 0.90 [95% CI: 0.83-0.98]) on multivariate analysis. Mean 1,25(OH)2D levels were significantly lower in women with preterm delivery and LBW infants. CONCLUSION: Lower bioactive vitamin D levels are related to PIH in HIV-infected women. This association may be related to the coexistence of abnormal placental vitamin D metabolism and abnormal placental implantation.

Leukoreduction and ultraviolet treatment reduce both the magnitude and the duration of the HLA antibody response.

BACKGROUND: Both leukoreduction and ultraviolet (UV) light treatment of blood products have been shown to reduce the incidence of HLA antibody development in recipients, but the impact of these treatments on the magnitude and persistence of the antibody response is less clear. STUDY DESIGN AND METHODS: Longitudinal samples from 319 subjects taken from four different study cohorts were evaluated for HLA antibodies to determine the effects of leukoreduction and UV treatment on HLA antibody generation and persistence. RESULTS: Subjects receiving leukoreduced or UV-treated blood products were less likely to generate Class I HLA antibodies, and those receiving leukoreduced blood were also less likely to generate Class II HLA antibodies. Among those receiving nonleukoreduced blood, 55% developed Class I HLA antibodies and 51% developed Class II HLA antibodies compared with 28% (Class I) and 15% (Class II) for those receiving leukoreduced blood and 36% (Class I) and 54% (Class II) for those receiving UV-treated blood. Among alloimmunized subjects, leukoreduction resulted in a significant twofold reduction in the magnitude of Class I HLA antibodies, and UV treatment resulted in a significant threefold reduction in the magnitude of Class II HLA antibodies. Both treatments resulted in shorter persistence of Class I HLA antibodies. CONCLUSIONS: These data demonstrate that leukoreduction and UV treatment of blood products results not only in a reduction in the incidence of HLA antibody production, but also in lower and more transient HLA antibody levels among sensitized transfusion recipients.

A comparison of MSM stigma, HIV stigma and depression in HIV-positive Latino and African American men who have sex with men (MSM).

Little research has examined differences in HIV stigma versus MSM stigma and the role of these stigmas in depression for HIV-positive Latino and African American men who have sex with men (MSM), subgroups disproportionately impacted by HIV in the US. MSM stigma, HIV stigma, depression, stress and social support were examined among HIV-positive Latino (n = 100) and African American (n = 99) MSM patients at five HIV clinics in Los Angeles County, California. In multiple regression models, Latino MSM had higher HIV stigma scores (p = 0.002) but lower MSM stigma scores (p < 0.001) compared to African American MSM. General support and stress were associated with HIV stigma (p < 0.001), but not MSM stigma. Both HIV stigma (p < 0.0001) and MSM stigma (p < 0.0001) were associated with depression. These data underscore the differences in experienced stigma for Latino and African American MSM and can be used to shape effective stigma reduction programs and behavioral counseling.

"We Are Not Different than Others": A Qualitative Study of the Lived Experience of Hispanic Adolescents and Young Adults Living with Perinatally Acquired HIV.

Though Hispanic youth with perinatally acquired HIV (PHIV) comprise 14% of those living with PHIV, little research has documented their lived experiences. Eighteen Hispanic adolescents and young adults (AYA) with PHIV were recruited from two pediatric infectious disease clinics in California (mean age = 20.8 years, 12 females and 6 males). Interview transcripts were analyzed for emergent themes regarding relationships, childbearing intentions, and future career aspirations. Participants acknowledged HIV as cause for rejection and fear of transmission from partners. Most desired children in the future. Those with children (n = 7) expressed a strong desire to continue their education for the benefit of their children. Many did not view HIV as a barrier to their career aspirations. HIV influenced their daily lives. However, the challenges of poverty, loss, and trauma also significantly shaped their well-being. Health care providers offered emotional and instrumental support which helped AYA make progress towards their goals.

The effect of prenatal highly active antiretroviral therapy on the transmission of congenital and perinatal/early postnatal cytomegalovirus among HIV-infected and HIV-exposed infants.

BACKGROUND: Before highly active antiretroviral therapy (HAART), congenital cytomegalovirus (CMV) rates were higher among human immunodeficiency virus (HIV)-exposed infants than unexposed infants. This study examines congenital and perinatal/early postnatal (P/EP) CMV among HIV-exposed infants pre- and post- HAART. METHODS: Infants born to HIV-infected women were evaluated for congenital CMV (CMV-positive culture in first 3 weeks of life) and P/EP CMV (positive culture in first 6 months of life). Prenatal maternal HAART was defined as triple antiretroviral therapy (ART) with at least 1 nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. RESULTS: Among 414 infants evaluated, 1678 CMV assessment days were completed (mean = 3 assessment days per infant). Congenital CMV rates did not differ by time period, HAART use, or infant HIV infection status. P/EP CMV rates were greater for the 1988-1996 birth cohort (17.9%) compared with the 1997-2002 birth cohort (8.9%) (P < .01), HIV-infected versus uninfected infants (P < .01), and infants with no maternal ART versus those with ART (P < .01). Controlling for potential confounders, P/EP CMV was associated with no maternal ART (odds ratio = 4.7; P < .01), and among those with no maternal ART, P/EP CMV was associated with maternal CD4 count ≤200 cells/µL (P < .01). For HIV-uninfected infants with P/EP CMV, symptoms including splenomegaly, lymphadenopathy, and hepatomegaly were associated with no maternal HAART versus those with HAART (41% vs 6%; P < .05). CONCLUSIONS: Although congenital CMV rates did not change, the post-HAART era showed reduced P/EP CMV and occurrence of related clinical symptoms. These findings underscore the importance of prenatal HAART for all HIV-infected pregnant women.

Detection of host immune responses in acute phase sera of spontaneous resolution versus persistent hepatitis C virus infection.

Prior to the identification of hepatitis C virus (HCV), transfusion-transmission was common. Viral transmission in subjects with a known date of infection allows the study of the immune responses to acute HCV infection. We analysed 39 soluble immune factors in serum samples from subjects with transfusion-transmitted HCV. Dynamic expression kinetics of interferon gamma-induced protein 10 (IP-10), tumour necrosis factor-alpha and interleukin (IL)-10 were observed during acute HCV infection. Serum IP-10 was the only analyte that was significantly elevated in HCV resolvers compared with uninfected controls. In individuals who progressed to chronic HCV elevated levels of IP-10 and IL-10 coincided with first significant alanine aminotransferase elevation and remained elevated during the first year of acute HCV infection. In addition to monitoring lack of reduction in viral load, serum levels of IP-10 and IL-10 expression during acute HCV infection may be useful biomarkers to predict the progress to chronic HCV.

HIV/HCV co-infection: pathogenesis, clinical complications, treatment, and new therapeutic technologies.

World-wide, hepatitis C virus (HCV) accounts for approximately 130 million chronic infections, with an overall 3% prevalence. Four to 5 million persons are co-infected with HIV. It is well established that HIV has a negative impact on the natural history of HCV, including a higher rate of viral persistence, increased viral load, and more rapid progression to fibrosis, end-stage liver disease, and death. Whether HCV has a negative impact on HIV disease progression continues to be debated. However, following the introduction of effective combination antiretroviral therapy, the survival of coinfected individuals has significantly improved and HCV-associated diseases have emerged as the most important co-morbidities. In this review, we summarize the newest studies regarding the pathogenesis of HIV/HCV coinfection, including effects of coinfection on HIV disease progression, HCV-associated liver disease, the immune system, kidney and cardiovascular disease, and neurologic status; and effectiveness of current anti-HIV and HCV therapies and proposed new treatment strategies.

Do social support, stress, disclosure and stigma influence retention in HIV care for Latino and African American men who have sex with men and women?

Limited research has examined the role that social support, stress, stigma and HIV disclosure play in retention in HIV care for African Americans and Latinos. Among 398 Latino and African American men who have sex with men (MSM) and women, the major predictor of retention in HIV care was disclosure of HIV status to more social network members (OR = 1.5; 95% CI: 1.1, 1.9). Among those who had disclosed (n = 334), female gender (OR = 1.8, 95% CI: 1.1, 3.1) and disclosure of HIV status to more network members (OR = 1.5, 95% CI: 1.1, 1.9) was associated with retention in HIV care. General stress was associated with retention in care (OR = 1.2; 95% CI: 1.1, 1.3) for African American MSM who had disclosed. More MSM-stigma was associated with poorer retention (OR = 0.9; 95% CI: 0.8, 0.9) for Latino MSM. Interventions that help patients safely disclose their HIV status to more social network members may improve HIV care retention as would social network counseling for Latino MSM to reduce MSM-stigma.

Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus.

BACKGROUND: Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression. METHODS: Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated. RESULTS: HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P < .001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8(+)CD38(+)DR(+) T cells (hazard ratio, 2.94 [95% confidence interval, 1.50-5.77]; P = .001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80-4.35]; P = .16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8(+)CD38(-)DR(+), CD4(+)CD38(-)DR(-), and CD8(+)CD38(-)DR(-) T cells were associated with a >60% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women. CONCLUSION: HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.

White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling.

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.

Transfusion transmission of highly prevalent commensal human viruses.

BACKGROUND: Anellovirus species Torque teno virus (TTV), Torque teno mini virus (TTMV), and Torque teno midi virus (TTMDV) and flavivirus GBV-C are highly prevalent and genetically diverse chronic human viral infections that have not yet been associated with disease. STUDY DESIGN AND METHODS: To determine if these commensal viruses are transmitted by blood transfusions, we genetically analyzed viral species in cryopreserved samples from blood donors and corresponding pre- and posttransfusion samples from recipients enrolled in the Transfusion-Transmitted Viruses Study cohort. RESULTS: All 24 individuals in 12 donor-recipient pairs were infected with TTV, while 16 were infected with TTMV, 15 with TTMDV, and four with GBV-C. None of the 12 informative cases of TTV transfusion or eight cases of TTMV transfusion, where the donor and recipient viruses could be genetically differentiated, resulted in detectable transmissions in which the donor viruses were detected in the recipient by direct sequencing of the polymerase chain reaction products. Of the five informative cases of TTMDV transfusion, including two cases of transfusion into TTMDV-negative recipients, one case of superinfection was seen with both the recipient and the donor viral variants detected in the transfusion recipient for at least 11 days posttransfusion. Three donor-recipient pairs were informative for GBV-C transmission with only one transfusion into a GBV-C-negative recipient resulting in a transiently detected infection. CONCLUSIONS: Transmission of the common commensal anelloviruses and GBV-C during transfusion was detected in 2 of 12 already infected or uninfected recipients. Underestimation of the true rate of viral transmission may be due to limitations in detecting donor viral variants present as minority variants in the already infected transfusion recipients.

Social support, stress and social network characteristics among HIV-positive Latino and African American women and men who have sex with men.

Social support and stress have been poorly characterized for persons with HIV, particularly for racial/ethnic minorities. To address this gap, data on general and HIV-specific support and stress and social network characteristics were collected for 399 African American and Latino women and men who have sex with men (MSM) in Los Angeles County. African American (mean = 41; SD = 17) and Latina (mean = 40; SD = 19) women reported the highest general support. Stress was also highest for Latina women (mean = 18; SD = 11) and higher compared to Latino and African American MSM. African American and Latina women reported receiving most of their social support and stress from family members, while African American and Latino MSM received their support and stress from friends and providers. Finally, Latina and African American women disclosed their HIV status to more network members and received more HIV-specific support compared to MSM. Interventions are needed to help Latino and African American MSM enhance their support networks to manage a stigmatized illness.

Low maternal vitamin D is associated with increased risk of congenital and peri/postnatal transmission of Cytomegalovirus in women with HIV.

BACKGROUND: CMV infection of the fetus or neonate can lead to devastating disease, and there are no effective prevention strategies to date. Vitamin D is a potent immunomodulator, supports antiviral immune responses, and plays an important role in placental immunity. METHODS: Retrospective cohort study to evaluate the impact of low maternal vitamin D on congenital and early postnatal transmission of CMV among HIV-infected, non-breastfeeding women and their HIV exposed but negative infants from an urban HIV clinic. Vitamin D panel was performed on stored maternal plasma obtained near time of delivery. Infant CMV testing at 0-6 months included urine and oral cultures, and/or serum polymerase chain reaction testing. RESULTS: Cohort included 340 mother-infant pairs (births 1991-2014). Among 38 infants (11%) with a CMV+ test between 0-6 months, 4.7% (14/300) had congenital CMV transmission (CMV+ test 0-3 weeks), and 7.6% (24/315) had peri/postnatal CMV (CMV+ test >3 weeks-6 months). Women with lower calcitriol (1,25-dihydroxyvitamin D), the active form of vitamin D, were more likely to have an infant with congenital (OR 12.2 [95% CI 1.61-92.2] P = 0.02) and peri/postnatal (OR 9.84 [95% CI 2.63-36.8] P = 0.0007) infections in multivariate analyses, independent of maternal HIV viral load and CD4 count. CONCLUSION: This study demonstrates an association between inadequate maternal calcitriol during pregnancy and increased congenital and early postnatal acquisition of CMV among non-breastfeeding women with HIV and their HIV negative infants.

Influence of sickle cell disease on susceptibility to HIV infection.

People with sickle cell disease (SCD) are reported to have low rates of HIV infection, slower progression to AIDS and lower HIV-associated mortality compared to the general population. Mechanisms of potential resistance to HIV in SCD are incompletely understood. We retrospectively reviewed the Transfusion Safety Study to compare HIV status between people with SCD and other congenital anemias who were routinely exposed to blood products during the high-risk period before HIV screening implementation. Non-SCD congenital anemia diagnosis was associated with a higher risk of HIV acquisition compared to SCD (OR 13.1 95%CI 1.6-108.9). In addition, we prospectively enrolled 30 SCD cases and 30 non-SCD controls to investigate potential mechanisms of resistance to HIV in SCD. CCR5 and CCR7 expression was lower and CD4 expression was higher on CD4+ T cells from SCD cases compared to controls. Surface expression of CD4+ T cell CXCR4, CD38 and HLA-DR did not differ between the groups. SCD CD4+ T cells were not less susceptible to HIV infection than controls. Levels of multiple cytokines were elevated in the SCD plasma, but SCD plasma compared to control plasma did not inhibit HIV infection of target cells. In conclusion, our epidemiological data support people with SCD being resistant to HIV infection. Potential mechanisms include lower CD4+ T cell expression of CCR5 and CCR7, balanced by increased CD4 expression and cytokine levels, which did not result in in vitro resistance to HIV infection. Further study is needed to define the risk and pathophysiology of HIV in persons with SCD.

Long-term serologic follow-up of isolated hepatitis B core antibody in HIV-infected and HIV-uninfected women.

BACKGROUND: Isolated antibody to hepatitis B core antigen (anti-HBc) is a common serologic finding in persons infected with human immunodeficiency virus (HIV), but the outcome and clinical significance are uncertain. METHODS: We performed repeated hepatitis B virus (HBV) serologic tests on women who participated in the Women's Interagency HIV Study and who had isolated anti-HBc at study entry. RESULTS: Repeated serologic tests were performed for 322 women (282 HIV-infected and 40 HIV-uninfected) at a median of 7.5 years after study entry. Seventy-one percent of women retained isolated anti-HBc serologic status, 20% acquired antibody to hepatitis B surface antigen (anti-HBs), and 2% acquired hepatitis B surface antigen (HBsAg). In unadjusted analysis, increasing age, injection drug use, and hepatitis C viremia were negatively associated with acquisition of anti-HBs. For HIV-infected women, predictors of acquisition of anti-HBs were an increase in CD4 cell count and the use of highly active antiretroviral therapy (HAART). Receipt of drugs with activity against HBV and self-reported HBV vaccination did not predict anti-HBs acquisition. In the multivariable regression model, HAART use remained a significant predictor of anti-HBs acquisition, whereas women with hepatitis C viremia were more likely to retain isolated anti-HBc serologic status. CONCLUSIONS: Isolated anti-HBc status remained stable over time for the majority of women, especially women with chronic hepatitis C virus infection. Development of anti-HBs was predicted by HAART use and an increase in CD4 cell count. We conclude that a proportion of HIV-infected women with isolated anti-HBc have prior natural HBV infection with anti-HBs that is at an undetectable level because of immune dysfunction. Isolated anti-HBc in the presence of chronic hepatitis C virus infection may be attributable to a different phenomenon, such as dysfunctional antibody production.

Factors associated with hepatitis C viremia in a large cohort of HIV-infected and -uninfected women.

BACKGROUND: Co-infection with hepatitis C virus (HCV) is common among HIV-infected women. OBJECTIVE: To further our understanding of the risk factors for HCV viremia and the predictors of HCV viral load among women. STUDY DESIGN: We investigated sociodemographic, immunologic, and virologic factors associated with presence and level of HCV viremia among 1049 HCV-seropositive women, 882 of whom were HIV-infected and 167 HIV-uninfected at their entry into the Women's Interagency HIV Study. RESULTS: Plasma HCV RNA was detected in 852 (81%) of these 1049 women (range: 1.2-7.8 log(10)copies/ml). HCV-viremic women were more likely to have an HIV RNA level >100,000 copies/ml (P=0.0004), to have reported smoking (P=0.01), or to be Black (P=0.005). They were less likely to have current or resolved hepatitis B infection. HCV RNA levels were higher in women who were >35 years old, or HIV-infected. Current smoking and history of drug use (crack/freebase cocaine, marijuana, amphetamines, or heroin) were each associated with both presence and level of viremia. CONCLUSIONS: Substance abuse counseling aimed at eliminating ongoing use of illicit drugs and tobacco may reduce clinical progression, improve response to treatment, and decrease HCV transmission by lowering levels of HCV viremia in women.

Systemic Immune Activation and HIV Shedding in the Female Genital Tract.

BACKGROUND: Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. METHODS: Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. RESULTS: In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02). CONCLUSIONS: The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV shedding, and transmission.

Impact of Hepatitis C Virus on the Circulating Levels of IL-7 in HIV-1 Coinfected Women.

OBJECTIVES: Hepatitis C virus (HCV) infection causes an alteration in T-cell maturation and activation in patients coinfected with human immunodeficiency virus (HIV). Because interleukin 7 (IL-7) is a major cytokine controlling T-cell homeostasis, we analyzed the potential influence of HCV coinfection on circulating IL-7 levels in HIV-infected women before and after highly active antiretroviral therapy (HAART). DESIGN AND METHODS: This prospective study included 56 HIV monoinfected, 55 HIV/HCV coinfected without HCV viremia, 132 HIV/HCV coinfected with HCV viremia, and 61 HIV/HCV-uninfected women for whom plasma levels of IL-7 were determined by enzyme-linked immunosorbent assay at 1 or more follow-up visits before and after HAART. Cross-sectional analyses of the associations between plasma IL-7 levels and HCV infection, demographic, clinical, and immunologic characteristics were evaluated using univariate and multivariate linear regression models before and after HAART. RESULTS: In multivariate models, IL-7 levels were significantly higher in coinfected HCV viremic women than in HIV monoinfected women (multiplicative effect = 1.48; 95% confidence interval: 1.01 to 2.16; P = 0.04) before HAART, but were similar between these two groups among women after HAART. In addition to HCV viremia, higher IL-7 levels were associated with older age (P = 0.02), lower CD4(+) T-cell count (P = 0.0007), and higher natural killer T-cell count (P = 0.02) in women before HAART. Among HAART-treated women, only lower CD4(+) T-cell count was significantly associated with IL-7 level (P = 0.006). CONCLUSIONS: Our data demonstrate that in HIV-infected women, circulating levels of IL-7 are strongly associated with CD4 T-cell depletion both before and after HAART. Our data also demonstrate that HCV viremia increases circulating IL-7 levels before HAART but not after HAART in coinfected women. This suggests that the effect of HCV on lymphopenia is abrogated by HAART.