Tracking the Trajectory of Functional Humoral Immune Responses Following Acute HIV Infection.

Increasing evidence points to a role for antibody-mediated effector functions in preventing and controlling HIV infection. However, less is known about how these antibody effector functions evolve following infection. Moreover, how the humoral immune response is naturally tuned to recruit the antiviral activity of the innate immune system, and the extent to which these functions aid in the control of infection, are poorly understood.

Topical Tenofovir Pre-exposure Prophylaxis and Mucosal HIV-Specific Fc-Mediated Antibody Activities in Women.

The RV144 HIV-vaccine trial highlighted the importance of envelope-specific non-neutralizing antibody (nNAb) Fc-mediated functions as immune correlates of reduced risk of infection. Since pre-exposure prophylaxis (PrEP) and HIV-vaccines are being used as a combination prevention strategy in at risk populations, the effects of PrEP on nNAb functions both mucosally and systemically remain undefined. Previous animal and human studies demonstrated reduced HIV-specific antibody binding avidity post-HIV seroconversion with PrEP, which in turn may affect antibody functionality.

Quotidian changes of genital tract cytokines in human immunodeficiency virus-1-infected women during the menstrual cycle.

The role of hormonal changes throughout the menstrual cycle on genital tract inflammation during chronic human immunodeficiency virus (HIV) infection is not well defined, but it has implications for HIV prevention. We assessed daily levels of 26 vaginal cytokines and chemokines from 15 women infected with HIV-1. Taking into account coexisting sexually transmitted infections, behavioral factors, and menstruation, this study illustrates cyclic patterns of granulocyte macrophage colony-stimulating factor, interferon-α2, interleukin (IL)-6, IL-10, macrophage inflammatory protein (MIP)-1α, MIP-1β, and tumor necrosis factor (TNF)-α.

HIV-1 maternal and infant variants show similar sensitivity to broadly neutralizing antibodies, but sensitivity varies by subtype.

Rationale: To protect against HIV infection, passively transferred and/or vaccine-elicited neutralizing antibodies (NAbs) need to effectively target diverse subtypes that are transmitted globally. These variants are a limited subset of those present during chronic infection and display some unique features. In the case of mother-to-child transmission (MTCT), transmitted variants tend to be resistant to neutralization by maternal autologous NAbs.

HIV-specific antibodies capable of ADCC are common in breastmilk and are associated with reduced risk of transmission in women with high viral loads.

There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities.

Breast milk HIV-1 RNA levels and female sex are associated with HIV-1-specific CD8+ T-cell responses in HIV-1-exposed, uninfected infants in Kenya.

Background: Although evidence supports a relationship between human immunodeficiency virus (HIV)-1 exposure and HIV-1-specific CD8(+) T cell responses, studies have not demonstrated a direct association between the quantity of HIV-1 to which a person is exposed and the presence or absence of a response.

Methods: From 1999 to 2005, maternal HIV-1 RNA levels were measured in blood, cervical secretions, and breast milk at delivery and 1 month after delivery. HIV-1-specific interferon (IFN)-γ Elispot assays were conducted to determine infant CD8(+) T-cell responses at 3 months of age.

The breadth and potency of passively acquired human immunodeficiency virus type 1-specific neutralizing antibodies do not correlate with the risk of infant infection.

Although a major goal of human immunodeficiency virus type 1 (HIV-1) vaccine efforts is to elicit broad and potent neutralizing antibodies (NAbs), there are no data that directly demonstrate a role for such NAbs in protection from HIV-1 infection in exposed humans. The setting of mother-to-child transmission provides an opportunity to examine whether NAbs provide protection from HIV-1 infection because infants acquire passive antibodies from their mothers prior to exposure to HIV-1 through breastfeeding. We evaluated the characteristics of HIV-1-specific NAbs in 100 breast-fed infants of HIV-1-positive mothers who were HIV-1 negative at birth and monitored them until age 2.

Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission.

Background: Antiretroviral resistance after short-course regimens used to prevent mother-to-child transmission has consequences for later treatment. Directly comparing the prevalence of resistance after short-course regimens of highly active antiretroviral therapy (HAART) and zidovudine plus single-dose nevirapine (ZDV/sdNVP) will provide critical information when assessing the relative merits of these antiretroviral interventions.

Methods: In a clinical trial in Kenya, pregnant women were randomized to receive either ZDV/sdNVP or a short-course of HAART through 6 months of breastfeeding.

Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1 (HIV-1)-infected children pre- and post-highly active antiretroviral therapy and revaccination.

Background: : HIV-1-infected children have lower response rates after measles and tetanus immunization than uninfected children. We determined the extent to which highly active antiretroviral therapy (HAART) augments vaccine immunity and promotes responses to revaccination.

Methods: : Previously immunized, antiretroviral-naive HIV-1-infected children were evaluated for immunity against measles and tetanus.

Maternal HLA homozygosity and mother-child HLA concordance increase the risk of vertical transmission of HIV-1.

Background: Mother-child human leukocyte antigen (HLA) concordance and maternal HLA homozygosity may increase the risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) risk by reducing infant immune responses.

Methods: We analyzed mother-child HLA concordance and maternal HLA homozygosity in a Kenyan perinatal cohort receiving antenatal zidovudine. HLA concordance was scored as the number of shared class I alleles, and relative risk estimates were adjusted for maternal HIV-1 load.

Longitudinal comparison of chemokines in breastmilk early postpartum among HIV-1-infected and uninfected Kenyan women.

Breastmilk chemokines have been associated with increased HIV-1 RNA levels in breastmilk and altered risk of mother-to-child HIV-1 transmission. To characterize CC and CXC chemokines in breastmilk postpartum, we collected breastmilk specimens at regular intervals for 6 months after delivery from women with and without HIV-1 infection and used commercial ELISA kits to measure breastmilk concentrations of MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha. Among 54 HIV-1-infected and 26 uninfected women, mean chemokine levels were compared cross-sectionally and longitudinally at days 5 and 10, and months 1 and 3 postpartum.

Breast milk alpha-defensins are associated with HIV type 1 RNA and CC chemokines in breast milk but not vertical HIV type 1 transmission.

Alpha-defensins are proteins exhibiting in vitro anti-HIV-1 activity that may protect against mother-to-child transmission of HIV-1 via breast milk. Correlates of alpha-defensins in breast milk and transmission risk were determined in a cohort of HIV-1-infected pregnant women in Nairobi followed for 12 months postpartum with their infants. Maternal blood was collected antenatally and at delivery for HIV-1 viral load and infant HIV-1 infection status was determined < 48 h after birth and at months 1, 3, 6, 9, and 12.