The Effects of Different HIV Type 1 Strains on Human Thymic Function

Studies of HIV-1-infected humans indicate that the thymus can be infected by HIV-1. In some of these patients, there is a significant CD4+ T cell decline and a faster disease progression. This phenomenon is more evident in pediatric patients who depend heavily on their thymus for generation of new T cells. We hypothesize that HIV-1 causes T cell regenerative failure within the thymus, which has a profound impact on disease progression. Building on our established human thymopoiesis model, we include dynamic interactions between different HIV-1 strains (R5 and X4) and thymocytes. Our results predict that thymic infection with different HIV-1 strains induces thymic dysfunction to varying degrees, contributing to differences in disease progression as observed in both HIV-1-infected children and adults. Thymic infection in children is more severe than in adults, particularly during X4 infection. This outcome is likely due to both a higher viral load and a more active thymus in pediatric patients. Our results also indicate that a viral strain switch from R5 to X4 induces further deterioration in thymopoiesis. We predict that both viral and host factors play key roles in controlling thymic infection, including strain virulence and health status of the thymus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63198/1/088922202320886280.pd

Influenza and Pregnant Women: Hospitalization Burden, United States, 1998–2002

Women in later stages of pregnancy are at increased risk for serious influenza-related morbidity; thus, universal influenza vaccination of pregnant women is recommended. However, vaccine uptake in the United States has been suboptimal. We previously described the burden of severe influenza-related morbidity during pregnancy in the United States by examining hospitalizations of pregnant women with respiratory illness during influenza season. Nondelivery hospitalizations with respiratory illness had significantly longer lengths of stay than those without respiratory illness. Hospitalization characteristics associated with greater likelihood of respiratory illness were the presence of a high-risk condition for which influenza vaccination is recommended, Medicaid/Medicare as primary expected payer, and hospitalization in a rural area. These findings may be explained by these women being at higher risk of influenza-related morbidity or reflect disparities in receipt of influenza immunization. Universal vaccination of pregnant women to decrease influenza-related morbidity should be encouraged.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63171/1/jwh.2006.15.891.pd

Complications of Common Gynecologic Surgeries among HIV-Infected Women in the United States

Objective. To compare frequencies of complications among HIV-infected and-uninfected women undergoing common gynecological surgical procedures in inpatient settings. Methods. We used 1994–2007 data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, a nationally representative sample of inpatient hospitalizations. Our analysis included discharge records of women aged ≥15 undergoing hysterectomy, oophorectomy, salpingectomy for ectopic pregnancy, bilateral tubal sterilization, or dilation and curettage. Associations between HIV infection status and surgical complications were evaluated in multivariable logistic regression models, adjusting for key covariates. Results. For each surgery, HIV infection was associated with experiencing ≥1 complication. Adjusted ORs ranged from 2.0 (95% confidence interval (CI): 1.7, 2.2) for hysterectomy with oophorectomy to 3.1 (95% CI: 2.4, 4.0) for bilateral tubal sterilization with no comorbidity present. HIV infection was positively associated with extended length of stay and infectious complications of all of the surgeries examined. For some surgeries, it was positively associated with transfusion and anemia due to acute blood loss. Among HIV-infected women, the odds of infectious and other complications did not decrease between 1994–2000 and 2001–2007. Conclusion. HIV infection was associated with elevated frequencies of complications of gynecologic surgeries in the US, even in the era of HAART

Pregnancy and infection [letter]

Pregnant women have an increased severity of infections with some organisms, including influenza virus, hepatitis E virus, herpes simplex virus, and malaria parasites. This review includes an update on immunologic alterations during pregnancy

Maternal Humoral Immune Correlates of Peripartum Transmission of Clade C HIV-1 in the Setting of Peripartum Antiretrovirals

ABSTRACT Despite the widespread use of antiretrovirals (ARV), more than 150,000 pediatric HIV-1 infections continue to occur annually. Supplemental strategies are necessary to eliminate pediatric HIV infections. We previously reported that maternal HIV envelope-specific anti-V3 IgG and CD4 binding site-directed antibodies, as well as tier 1 virus neutralization, predicted a reduced risk of mother-to-child transmission (MTCT) of HIV-1 in the pre-ARV era U.S.-based Women and Infants Transmission Study (WITS) cohort. As the majority of ongoing pediatric HIV infections occur in sub-Saharan Africa, we sought to determine if the same maternal humoral immune correlates predicted MTCT in a subset of the Malawian Breastfeeding, Antiretrovirals, and Nutrition (BAN) cohort of HIV-infected mothers ( n = 88, with 45 transmitting and 43 nontransmitting). Women and infants received ARV at delivery; thus, the majority of MTCT was in utero (91%). In a multivariable logistic regression model, neither maternal anti-V3 IgG nor clade C tier 1 virus neutralization was associated with MTCT. Unexpectedly, maternal CD4 binding-site antibodies and anti-variable loop 1 and 2 (V1V2) IgG were associated with increased MTCT, independent of maternal viral load. Neither infant envelope (Env)-specific IgG levels nor maternal IgG transplacental transfer efficiency was associated with transmission. Distinct humoral immune correlates of MTCT in the BAN and WITS cohorts could be due to differences between transmission modes, virus clades, or maternal antiretroviral use. The association between specific maternal antibody responses and in utero transmission, which is distinct from potentially protective maternal antibodies in the WITS cohort, underlines the importance of investigating additional cohorts with well-defined transmission modes to understand the role of antibodies during HIV-1 MTCT

A randomized clinical trial on the effects of progestin contraception in the genital tract of HIV-infected and uninfected women in Lilongwe, Malawi: Addressing evolving research priorities

Hormonal contraception is central in the prevention of unintended pregnancy; however there are concerns that certain methods may increase the risk of HIV acquisition and transmission. Hormonal contraceptives may modify the genital mucosa in several ways, however the mechanisms are incompletely understood. Few studies have examined genital HIV shedding prospectively before and after initiation of hormonal contraception. The effects of hormonal contraception on genital HIV shedding in the setting of antiretroviral therapy (ART) are also unknown. We designed a pilot clinical trial in which HIV-infected and uninfected women were randomized to either depot medroxyprogesterone acetate (DMPA) injectable or levonorgestrel (LNG) implant in Lilongwe, Malawi. The objectives were to: 1) assess the effect and compare the impact of type of progestin contraception (injectable versus implant) on HIV genital shedding among HIV-infected women, 2) assess the effect and compare the impact of type of progestin contraception on inflammatory/immune markers in the genital tract of both HIV-infected and uninfected women, and 3) assess the interaction of progestin contraception and ART by examining contraceptive efficacy and ART efficacy. An additional study aim was to determine the feasibility and need for a larger study of determinants of HIV transmissibility and acquisition

Eliminating Preventable HIV-Related Maternal Mortality in Sub-Saharan Africa: What Do We Need to Know?

Introduction: HIV makes a significant contribution to maternal mortality, and women living in sub-Saharan Africa are most affected. International commitments to eliminate preventable maternal mortality and reduce HIV-related deaths among pregnant and postpartum women by 50% will not be achieved without a better understanding of the links between HIV and poor maternal health outcomes and improved health services for the care of women living with HIV (WLWH) during pregnancy, childbirth, and postpartum. Methods: This article summarizes priorities for research and evaluation identified through consultation with 30 international researchers and policymakers with experience in maternal health and HIV in sub-Saharan Africa and a review of the published literature. Results: Priorities for improving the evidence about effective interventions to reduce maternal mortality and improve maternal health among WLWH include better quality data about causes of maternal death among WLWH, enhanced and harmonized program monitoring, and research and evaluation that contributes to improving: (1) clinical management of pregnant and postpartum WLWH, including assessment of the impact of expanded antiretroviral therapy on maternal mortality and morbidity, (2) integrated service delivery models, and (3) interventions to create an enabling social environment for women to begin and remain in care. Conclusions: As the global community evaluates progress and prepares for new maternal mortality and HIV targets, addressing the needs of WLWH must be a priority now and after 2015. Research and evaluation on maternal health and HIV can increase collaboration on these 2 global priorities, strengthen political constituencies and communities of practice, and accelerate progress toward achievement of goals in both areas

Health outcomes of HIV-exposed uninfected African infants

To evaluate severe (grade 3/4) morbidity and mortality in HIV-exposed, uninfected infants