Meningococcal Disease in Patients With Human Immunodeficiency Virus Infection: A Review of Cases Reported Through Active Surveillance in the United States, 2000-2008.

BackgroundAlthough human immunodeficiency virus (HIV) infection is an established risk factor for several bacterial infections, the association between HIV infection and meningococcal disease remains unclear.MethodsExpanded chart reviews were completed on persons with meningococcal disease and HIV infection reported from 2000 through 2008 from 9 US sites participating in an active population-based surveillance system for meningococcal disease. The incidence of meningococcal disease among patients meeting Centers for Disease Control and Prevention acquired immune deficiency syndrome (AIDS) surveillance criteria was estimated using data from the National HIV Surveillance System for the participating sites.ResultsThirty-three cases of meningococcal disease in individuals with HIV infection were reported from participating sites, representing 2.0% of all reported meningococcal disease cases. Most (75.8%) persons with HIV infection were adult males aged 25 to 64 years old. Among all meningococcal disease cases aged 25 to 64 years old, case fatality ratios were similar among HIV-infected and HIV-uninfected persons (13.3% vs 10.6%; P = .6). The cumulative, mean incidence of meningococcal disease among patients aged 25 to 64 years old with HIV infection ever classified as AIDS was 3.5 cases per 100000 person years (95% confidence interval [CI], 2.1-5.6), compared with 0.3 cases per 100000 person years (95% CI, 0.3-0.3) for persons of the same age group not reported to have AIDS (relative risk = 12.9; 95% CI, 7.9-20.9).ConclusionsIndividuals with HIV infection meeting the AIDS surveillance case definition have a higher incidence of meningococcal disease compared with the general adult population

Relationship between levels of inflammatory cytokines in the genital tract and CD4+ cell counts in women with acute HIV-1 infection.

Inflammatory responses at mucosal surfaces after human immunodeficiency virus type 1 (HIV-1) transmission may influence disease outcome. We evaluated levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha, IL-8, IL-10, and IL-12 in genital tract and plasma specimens from 44 women with acute HIV infection and 29 HIV-negative control women (13 of whom were women in the acute HIV infection cohort who had preinfection samples available for analysis). Women with acute HIV infection had significantly elevated levels of IL-6, IL-10, and IL-12 in genital tract specimens and elevated levels of IL-1beta, IL-8, and IL-10 in plasma specimens, compared with HIV-negative control women. Levels of IL-1beta, IL-6, and IL-8 in cervicovaginal specimens from women with acute HIV infection showed a significant inverse correlation with systemic CD4(+) cell counts, suggesting that mucosal inflammation is associated with low CD4(+) cell counts during acute HIV infection

Granulocytic myeloid-derived suppressor cells increased in early phases of primary HIV infection depending on TRAIL plasma level

Background It has been demonstrated that Myeloid Derived Suppressor Cells (MDSC) are expanded in HIV-1 infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study we evaluated the frequency of MDSC in patients during primary HIV infection, and factors involved in MDSC control. Methods Patients with primary (PHI) and chronic (CHI) HIV infection were enrolled. PHI staging was performed according to Fiebig classification, and circulating MDSC frequency and function were evaluated by flow cytometry. Cytokine levels were evaluated by Luminex technology. Results We found that granulocytic MDSC (Gr-MDSC) frequency was higher in PHI compared to healthy donors, but lower than CHI. Interestingly, Gr-MDSC expansion was observed in the early phases of HIV infection (Fiebig II/III), but it was not associated to HIV viral load and CD4 T cell count. Interestingly, in PHI Gr-MDSC frequency was inversely correlated with plasmatic level of TRAIL, while a direct correlation was observed in CHI. Further, lower level of GMCSF was observed in PHI compared with CHI. In vitro experiments demonstrated that, differently from CHI, recombinant TRAIL induced apoptosis of Gr-MDSC from PHI, can effect that can be abrogated by GM-CSF. Conclusion We found that Gr-MDSC are expanded early during primary HIV infection and may be regulated by TRAIL and GM-CSF levels. These findings shed light on the fine mechanisms regulating the immune system during HIV infection, and open new perspectives for immune-based strategies

Stem-cell-based gene therapy for HIV infection.

Despite the enormous success of combined anti-retroviral therapy, HIV infection is still a lifelong disease and continues to spread rapidly worldwide. There is a pressing need to develop a treatment that will cure HIV infection. Recent progress in stem cell manipulation and advancements in humanized mouse models have allowed rapid developments of gene therapy for HIV treatment. In this review, we will discuss two aspects of HIV gene therapy using human hematopoietic stem cells. The first is to generate immune systems resistant to HIV infection while the second strategy involves enhancing anti-HIV immunity to eliminate HIV infected cells

Viral dynamics of acute HIV-1 infection.

Viral dynamics were intensively investigated in eight patients with acute HIV infection to define the earliest rates of change in plasma HIV RNA before and after the start of antiretroviral therapy. We report the first estimates of the basic reproductive number (R(0)), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted. The mean initial viral doubling time was 10 h, and the peak of viremia occurred 21 d after reported HIV exposure. The spontaneous rate of decline (alpha) was highly variable among individuals. The phase 1 viral decay rate (delta(I) = 0.3/day) in subjects initiating potent antiretroviral therapy during acute HIV infection was similar to estimates from treated subjects with chronic HIV infection. The doubling time in two subjects who discontinued antiretroviral therapy was almost five times slower than during acute infection. The mean basic reproductive number (R(0)) of 19.3 during the logarithmic growth phase of primary HIV infection suggested that a vaccine or postexposure prophylaxis of at least 95% efficacy would be needed to extinguish productive viral infection in the absence of drug resistance or viral latency. These measurements provide a basis for comparison of vaccine and other strategies and support the validity of the simian immunodeficiency virus macaque model of acute HIV infection

Social learning, selection, and HIV infection: Evidence from Malawi

"This paper examines social learning regarding HIV infection, using HIV test results and sibling death data from Malawi. In the analysis, we compare hypotheses on social learning, selection. and common factors. Empirical results show that young women are less likely to be HIV-infected if they observed prime-age deaths among their siblings, whereas HIV infection is found to be positively related to prime-age sibling deaths among older women. This supports the social-learning hypothesis. Notably, schooling reinforces the social-learning effect of sibling deaths on HIV infection in women regardless of age. The above findings are robust to age (cohort) effects and unobserved location factors." from authors' abstractSocial learning, HIV infection, AIDS (Disease) Africa, Sub-Saharan, siblings,

Overestimating HIV infection:

In the absence of HIV testing, how do rural Malawians assess their HIV status? In this paper, we use a unique dataset that includes respondents’ HIV status as well as their subjective likelihood of HIV infection. These data show that many rural Malawians overestimate their likelihood of current HIV infection. The discrepancy between actual and perceived status raises an important question: Why are so many wrong? We begin by identifying determinants of self-assessed HIV status, and then compare these assessments with HIV biomarker results. Finally, we ask what characteristics of individuals are associated with errors in self-assessments.accuracy of perceived HIV status, AIDS/HIV, perceived risk, Sub-Saharan Africa

Sexual and marital trajectories and HIV infection among ever-married women in rural Malawi.

OBJECTIVE: To explore how sexual and marital trajectories are associated with HIV infection among ever-married women in rural Malawi. METHODS: Retrospective survey data and HIV biomarker data for 926 ever-married women interviewed in the Malawi Diffusion and Ideational Change Project were used. The associations between HIV infection and four key life course transitions considered individually (age at sexual debut, premarital sexual activity, entry into marriage and marital disruption by divorce or death) were examined. These transitions were then sequenced to construct trajectories that represent the variety of patterns in the data. The association between different trajectories and HIV prevalence was examined, controlling for potentially confounding factors such as age and region. RESULTS: Although each life course transition taken in isolation may be associated with HIV infection, their combined effect appeared to be conditional on the sequence in which they occurred. Although early sexual debut, not marrying one's first sexual partner and having a disrupted marriage each increased the likelihood of HIV infection, their risk was not additive. Women who both delayed sexual debut and did not marry their first partner are, once married, more likely to experience marital disruption and to be HIV-positive. Women who marry their first partner but who have sex at a young age, however, are also at considerable risk. CONCLUSIONS: These findings identify the potential of a life course perspective for understanding why some women become infected with HIV and others do not, as well as the differentials in HIV prevalence that originate from the sequence of sexual and marital transitions in one's life. The analysis suggests, however, the need for further data collection to permit a better examination of the mechanisms that account for variations in life course trajectories and thus in lifetime probabilities of HIV infection