Human Immunodeficiency Virus Exposure Research Articles

The effects of human immunodeficiency virus infection on the expression of the drug efflux proteins P-glycoprotein and breast cancer resistance protein in a human intestine model.

In human immunodeficiency virus (HIV) infection, decreased penetration of antiretroviral drugs is postulated to contribute to HIV persistence within lymphoid-rich regions of the gastrointestinal (GI) tract. However, mechanistic explanations for this phenomenon remain unclear. Specifically, investigations of HIV effects on drug efflux proteins within intestinal models are minimal. Using an in-vitro co-culture model of the GI tract, the effects of HIV infection on drug efflux proteins, P-glycoprotein and breast cancer resistance protein (BCRP) were evaluated. The influence of the HIV-1 protein, Tat, and oxidative stress on P-glycoprotein and BCRP was also evaluated. P-glycoprotein expression demonstrated an HIV-induced upregulation in Caco-2 cells over time for cells grown in co-culture with resting lymphocytes. BCRP overall expression increased with HIV exposure in activated primary human lymphocytes co-cultured with Caco-2 cells. Tat treatment resulted in no significant alterations in P-glycoprotein (43% increase), BCRP expression, or oxidative stress. HIV exposure within an in-vitro intestinal model resulted in increases in P-glycoprotein and BCRP in a cell-specific manner. Additionally, observed changes were not mediated by Tat. Collectively, these results suggest that alterations in BCRP and P-glycoprotein may contribute, in part, to decreased antiretroviral concentrations within the gut-associated lymphoid tissue of the GI tract in HIV infection.

Dose response for starting and stopping HIV preexposure prophylaxis for men who have sex with men.

This study estimated the number of daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) doses required to achieve and maintain (after discontinuation) intracellular drug concentrations that protect against human immunodeficiency virus (HIV) infection for men who have sex with men (MSM). Tenofovir diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cells (PBMCs) and rectal mononuclear cells from an intensive pharmacokinetic study ("Cell-PrEP" [preexposure prophylaxis]) of 30 days of daily TDF/FTC followed by 30 days off drug were evaluated. A regression formula for HIV risk reduction derived from PBMCs collected in the preexposure prophylaxis initiative study was used to calculate inferred risk reduction. The time required to reach steady state for TFV-DP in rectal mononuclear cells was also determined. Twenty-one HIV-uninfected adults participated in Cell-PrEP. The inferred HIV risk reduction, based on PBMC TFV-DP concentration, reached 99% (95% confidence interval [CI], 69%-100%) after 5 daily doses, and remained >90% for 7 days after stopping drug from steady-state conditions. The proportion of participants reaching the 90% effective concentration (EC90) was 77% after 5 doses and 89% after 7 doses. The percentage of steady state for natural log [TFV-DP] in rectal mononuclear cells was 88% (95% CI, 66%-94%) after 5 doses and 94% (95% CI, 78%-98%) after 7 doses. High PrEP activity for MSM was achieved by approximately 1 week of daily dosing. Although effective intracellular drug concentrations persist for several days after stopping PrEP, a reasonable recommendation is to continue PrEP dosing for 4 weeks after the last potential HIV exposure, similar to recommendations for postexposure prophylaxis.

Treatment Failures and Excess Mortality Among HIV-Exposed, Uninfected Children With Pneumonia.

Human immunodeficiency virus (HIV)-exposed, uninfected (HIV-EU) children are at increased risk of infectious illnesses and mortality compared with children of HIV-negative mothers (HIV-unexposed). However, treatment outcomes for lower respiratory tract infections among HIV-EU children remain poorly defined. We conducted a hospital-based, prospective cohort study of N = 238 children aged 1-23 months with pneumonia, defined by the World Health Organization. Children were recruited within 6 hours of presentation to a tertiary hospital in Botswana. The primary outcome--treatment failure at 48 hours--was assessed by an investigator blinded to HIV exposure status. Median age was 6.0 months; 55% were male. One hundred fifty-three (64%) children were HIV-unexposed, 64 (27%) were HIV-EU, and 20 (8%) were HIV-infected; the HIV exposure status of 1 child could not be established. Treatment failure at 48 hours occurred in 79 (33%) children, including in 36 (24%) HIV-unexposed, 30 (47%) HIV-EU, and 12 (60%) HIV-infected children. In multivariable analyses, HIV-EU children were more likely to fail treatment at 48 hours (risk ratio [RR]: 1.83, 95% confidence interval [CI]: 1.27-2.64, P = .001) and had higher in-hospital mortality (RR: 4.31, 95% CI: 1.44-12.87, P = .01) than HIV-unexposed children. Differences in outcomes by HIV exposure status were observed only among children under 6 months of age. HIV-EU children more frequently received treatment with a third-generation cephalosporin, but this did not reduce the risk of treatment failure in this group. HIV-EU children with pneumonia have higher rates of treatment failure and in-hospital mortality than HIV-unexposed children during the first 6 months of life. Treatment with a third-generation cephalosporins did not improve outcomes among HIV-EU children.

Rewards and challenges of providing HIV testing and counselling services: health worker perspectives from Burkina Faso, Kenya and Uganda.

The rapid scale-up of human immunodeficiency virus (HIV) testing, counselling and treatment throughout sub-Saharan Africa has raised questions about how to protect patients' rights to consent, confidentiality, counselling and care in resource-constrained settings. The Multi-country African Testing and Counselling for HIV (MATCH) study investigated client and provider experiences with different modes of testing in sub-Saharan Africa. One component of that study was a survey of 275 HIV service providers in Burkina Faso, Kenya and Uganda that gathered quantifiable indicators and qualitative descriptions using a standardized instrument. This article presents provider perspectives on the challenges of obtaining consent, protecting confidentiality, providing counselling and helping clients manage disclosure. It also explores health workers' fear of infection within the workplace and their reports on discrimination against HIV clients within health facilities. HIV care providers in Burkina Faso, Kenya and Uganda experienced substantial rewards from their work, including satisfaction from saving lives and gaining professional skills. They also faced serious resource constraints, including staff shortages, high workloads, lack of supplies and inadequate infrastructure, and they expressed concerns about accidental exposure. Health workers described heavy emotional demands from observing clients suffer emotional, social and health consequences of being diagnosed with HIV, and also from difficult ethical dilemmas related to clients who do not disclose their HIV status to those around them, including partners. These findings suggest that providers of HIV testing and counselling need more resources and support, including better protections against HIV exposure in the workplace. The findings also suggest that health facilities could improve care by increasing attention to consent, privacy and confidentiality and that health policy makers and ethicists need to address some unresolved ethical dilemmas related to confidentiality and non-disclosure, and translate those discussions into better guidance for health workers.

Factors Associated With Isolated Right Heart Failure in Women: A Pilot Study From Western Kenya

BackgroundSmall observational studies have found that isolated right heart failure (IRHF) is prevalent among women of sub-Saharan Africa. Further, several risk factors for the development of IRHF have been identified. However, no similar studies have been conducted in Kenya. ObjectiveWe hypothesized that specific environmental exposures and comorbidities were associated with IRHF in women of western Kenya. MethodsWe conducted a case-control study at a referral hospital in western Kenya. Cases were defined as women at least 35 years old with IRHF. Control subjects were similarly aged volunteers without IRHF. Exclusion criteria in both groups included history of tobacco use, tuberculosis, or thromboembolic disease. Participants underwent echocardiography, spirometry, 6-min walk test, rest/exercise oximetry, respiratory health interviews, and human immunodeficiency virus (HIV) testing. Home visits were performed to evaluate kitchen ventilation, fuel use, and cook smoke exposure time, all surrogate measures of indoor air pollution (IAP). A total of 31 cases and 65 control subjects were enrolled. Surrogate measures of indoor air pollution were not associated with IRHF. However, lower forced expiratory volume at 1 s percent predicted (adjusted odds ratio [AOR]: 2.02, 95% confidence interval [CI]: 1.27 to 3.20; p = 0.004), HIV positivity (AOR: 40.4, 95% CI: 3.7 to 441; p < 0.01), and self-report of exposure to occupational dust (AOR: 3.9, 95% CI: 1.14 to 14.2; p = 0.04) were associated with IRHF. In an analysis of subgroups of participants with and without these factors, lower kitchen ventilation was significantly associated with IRHF among participants without airflow limitation (AOR: 2.63 per 0.10 unit lower ventilation, 95% CI: 1.06 to 6.49; p = 0.04), without HIV (AOR: 2.55, 95% CI: 1.21 to 5.37; p = 0.02), and without occupational dust exposure (AOR: 2.37, 95% CI: 1.01 to 5.56; p = 0.05). ConclusionsIn this pilot study among women of western Kenya, lower kitchen ventilation, airflow limitation, HIV, and occupational dust exposure were associated with IRHF, overall or in participant subgroups. Direct or indirect causality requires further study.

Hearing sensitivity in perinatally HIV-infected children

Research on the effects of perinatal human immunodeficiency virus (HIV) exposure on hearing sensitivity is increasing. This is important because hearing loss can delay language and communication development in young children. The purpose of this project was to evaluate hearing sensitivity characteristics in HIV+ and HIV- children.

Patient attrition between the emergency department and clinic among individuals presenting for HIV nonoccupational postexposure prophylaxis.

Nonoccupational postexposure prophylaxis (nPEP) is recommended after a sexual or parenteral exposure to human immunodeficiency virus (HIV). Patients frequently seek care in an emergency department (ED) after an exposure and are usually referred to an HIV clinic for further management. There have been few data on determinants of attrition after presentation to EDs for nPEP. From July 2010 to June 2011, we prospectively recorded all referrals to nPEP programs from 2 large EDs at 2 academic medical centers in Boston, Massachusetts. Data were recorded on patient demographics, nature of potential HIV exposures, referrals to and attendance at HIV clinics, and reported completion of 28 days of antiretroviral therapy (ART). Multivariable logistic regression was used to evaluate risk factors for (1) patient attrition between the ED and HIV clinic follow-up and (2) documented completion of ART. Of 180 individuals who were referred to clinic follow-up for nPEP care from the ED, 98 (54.4%) attended a first nPEP clinic visit and 43 (23.9%) had documented completion of a 28-day course of ART. Multivariable analysis revealed older age (adjusted odds ratio [aOR], 0.96; 95% confidence interval [CI], .93-.99) and self-payment (aOR, 0.32; 95% CI, .11-.97) were significant predictors for failing to attend an initial HIV clinic appointment. Women were less likely than men to complete a 28-day ART regimen (aOR, 0.34; 95% CI, .15-.79). Commonly used nPEP delivery models may not be effective for all patients who present with nonoccupational exposures to HIV. Interventions are needed to improve rates of follow-up and completion of nPEP to reduce the risk of preventable HIV infections.

Risk factors for mortality among human immunodeficiency virus-exposed and unexposed infants admitted to a neonatal intensive care unit in Botswana

Newborns admitted to neonatal units (NNUs) in resource-limited settings face a high risk of mortality, but the epidemiology of these deaths is poorly understood. We describe risk factors for NNU mortality in an area with high prevalence of human immunodeficiency virus (HIV). We performed a prospective cohort study of infants admitted to the NNU at a public referral hospital in Gaborone, Botswana. The primary outcome was neonatal death, defined as death within 28 days of a live delivery. Cox proportional hazard models were used to evaluate risk factors for mortality. From October 2008 to April 2009, 449 neonates were admitted to the NNU. Cumulative mortality was 24.5% (110/449). Factors associated with increased risk of death included lack of enteral feeding (hazard ratio (HR) 18.8, 95% confidence interval (CI) 10.3, 34.2), gestational age <28 weeks (HR 2.0, 95% CI 1.1, 3.8) and Apgar score <7 at 10 min (HR 2.5, 95% CI 1.5, 4.2). Among 348 (78%) infants who were fed, there was no difference in mortality between infants who were breastfed compared with those who were formula fed or had mixed feeding (P = 0.76). There was no significant mortality difference by HIV exposure status; 35 (28%) of 128 HIV-exposed infants died compared with 55 (21%) of 272 HIV-unexposed infants (P = 0.19). This study identified low Apgar scores, extreme prematurity and lack of enteral feeding as the most important risk factors for mortality in this NNU setting. HIV exposure and formula feeding were not significantly associated with death in neonates who were very ill.

Innate immune responses to HIV infection in the central nervous system

Human immunodeficiency virus (HIV) invades the brain early during infection and generates a chronic inflammatory microenvironment that can eventually result in neurological disease, even in the absence of significant viral replication. Thus, HIV-1 infection of the brain has been characterized both as a neuroimmunological and neurodegenerative disorder. While the brain and central nervous system (CNS) have historically been regarded as immune privileged or immunologically quiescent, newer concepts of CNS immunity suggest an important if not defining role for innate immune responses generated by glial cells. Innate immunity may be the first line of defense against HIV infection of the brain and CNS, with multiple cellular elements providing responses that can be anti-viral and neuroprotective, but also potentially neurotoxic, impairing neurogenesis and promoting neuronal apoptosis. To investigate the effects of HIV exposure on neurogenesis and neuronal survival, we have studied the responses of human neuroepithelial progenitor (NEP) cells, which undergo directed differentiation into astrocytes and neurons in vitro. We identified a group of genes that were differentially expressed in NEP-derived cells during virus exposure. This included genes that are strongly related to interferon-induced responses and antigen presentation. Moreover, we observed that the host factor apolipoprotein E influences the innate immune response expressed by these cells, with a more robust response in the apolipoprotein E3/E3 genotype cultures compared to the apolipoprotein E3/E4 counterparts. Thus, neuroepithelial progenitors and their differentiated progeny recognize HIV and respond to it by mounting an innate immune response with a vigor that is influenced by the host factor apolipoprotein E.

Survival analysis of acquired immune deficiency syndrome patients with and without hepatitis C virus infection at a reference center for sexually transmitted diseases/acquired immune deficiency syndrome in São Paulo, Brazil

IntroductionSurvival of patients with acquired immune deficiency syndrome has improved with combination antiretroviral therapy; mortality due to liver diseases, however, has also increased in these patients. ObjectivesTo estimate the accumulated probability of survival in human immunodeficiency virus–hepatitis C virus coinfected and non-coinfected patients and to investigate factors related to acquired immune deficiency syndrome patients’ survival. MethodsNon-concurrent cohort study using data from surveillance information systems of acquired immune deficiency syndrome patients over 13 years of age. Hepatitis C and B, human immunodeficiency virus exposure category, CD4+ T cell count, age group, schooling, race, sex, and four acquired immune deficiency syndrome diagnosis periods were studied. Kaplan–Meier survival analysis and Cox model with estimates of the hazard ratio and 95% confidence interval were used. ResultsOf the total 2864 individuals included, with median age was 35 years, 219 died (7.5%), and 358 (12.5%) were human immunodeficiency virus–hepatitis C virus coinfected. The accumulated probability of survival in human immunodeficiency virus–hepatitis C virus coinfected patients, after acquired immune deficiency syndrome diagnosis, at 120 months, was 0%, 38.9%, 83.8% in 1986–1993, 1994–1996, 1997–2002, respectively, and 92.8% at 96 months in 2003–2010; survival in non-coinfected patients at 120 months was 80%, 90.2%, 94% in 1986–1993, 1994–1996, 1997–2002, respectively, and 94.1% at 96 months in 2003–2010. In the multivariate model the following variables were predictive of death: hepatitis C virus coinfection (hazard ratio=2.7; confidence interval 2.0–3.6); Hepatitis B virus coinfection (hazard ratio=2.4; confidence interval 1.7–3.6); being ≥50 years old (hazard ratio=2.3; confidence interval 1.3–3.8); having 8–11 years of schooling (hazard ratio=1.6; confidence interval 1.1–2.3), having 4–7 years of schooling (hazard ratio=1.9; confidence interval 1.3–2.8) and having up to 3 years of schooling (hazard ratio=3.3; confidence interval 2.0–5.5). ConclusionsAmong patients diagnosed after 1996, there was a significant increase in the cumulative probability of survival in human immunodeficiency virus–hepatitis C virus coinfected individuals; among those diagnosed with acquired immune deficiency syndrome from 2003 to 2010, this probability was similar between coinfected and non-coinfected patients.

Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda.

HIV susceptibility is heterogeneous, with some HIV-exposed but seronegative (HESN) individuals remaining uninfected despite repeated exposure. Previous studies in the cervix have shown that reduced HIV susceptibility may be mediated by immune alterations in the genital mucosa. However, immune correlates of HIV-exposure without infection have not been investigated in the foreskin. We collected sub-preputial swabs and foreskin tissue from HESN (n=20) and unexposed control (n=57) men undergoing elective circumcision. Swabs were assayed for HIV-neutralizing IgA, innate antimicrobial peptides, and cytokine levels. Functional T cell subsets from foreskin tissue were assessed by flow cytometry. HESN foreskins had elevated α-defensins (3027 vs. 1795 pg/ml, p=0.011) and HIV-neutralizing IgA (50.0 vs. 13.5% of men, p=0.019). Foreskin tissue from HESN men contained a higher density of CD3 T cells (151.9 vs. 69.9 cells/mm2, p=0.018), but a lower proportion of these were Th17 cells (6.12 vs. 8.04% of CD4 T cells, p=0.007), and fewer produced TNFα (34.3 vs. 41.8% of CD4 T cells, p=0.037; 36.9 vs. 45.7% of CD8 T cells, p=0.004). A decrease in the relative abundance of susceptible CD4 T cells and local TNFα production, in combination with HIV-neutralizing IgA and α-defensins, may represent a protective immune milieu at a site of HIV exposure.

Teachers’ Perspectives on Sexuality and Sexuality Education of Learners with Intellectual Disabilities in Nigeria

Literature indicates a knowledge gap in the preparedness of teachers to deliver sexuality and human immunodeficiency virus (HIV) prevention education to learners with intellectual disabilities in Africa. This paper reports on teachers’ opinions on sexuality of Nigerian learners with intellectual disabilities and awareness of their risk of HIV infection. The study utilized key informant interviews with 12 teachers to explore their views on the sexuality and risk of HIV exposure of learners with intellectual disabilities in special schools across Oyo State, Nigeria. Interview scripts were analyzed using interpretative phenomenological analysis. Teachers considered learners with intellectual disabilities as ‘hypersexual’ and incapable of intimate relationships. Learners with intellectual disabilities were reported to be at risk of exposure to HIV infection due to sexual abuse, transactional sex and lack of sexuality and HIV education. Teachers expressed confidence to deliver sexuality and HIV education but lacked skills to communicate relevant information to learners with intellectual disabilities in accessible formats. Teachers’ negative attitudes, misconception and lack of skills to deliver sexuality education to learners with intellectual disabilities have to be addressed through training. Further studies are needed to provide baseline information for developing a tailored sexuality and HIV education for Nigerian learners with different types of disabilities.

The oral mucosa immune environment and oral transmission of HIV/SIV

The global spread of human immunodeficiency virus (HIV) is dependent on the ability of this virus to efficiently cross from one host to the next by traversing a mucosal membrane. Unraveling how mucosal exposure of HIV results in systemic infection is critical for the development of effective therapeutic strategies. This review focuses on understanding the immune events associated with the oral route of transmission (via breastfeeding or sexual oral intercourse), which occurs across the oral and/or gastrointestinal mucosa. Studies in both humans and simian immunodeficiency virus (SIV) monkey models have identified viral changes and immune events associated with oral HIV/SIV exposure. This review covers our current knowledge of HIV oral transmission in both infants and adults, the use of SIV models in understanding early immune events, oral immune factors that modulate HIV/SIV susceptibility (including mucosal inflammation), and interventions that may impact oral HIV transmission rates. Understanding the factors that influence oral HIV transmission will provide the foundation for developing immune therapeutic and vaccine strategies that can protect both infants and adults from oral HIV transmission.

The Effects of Social Determinants on Black Women’s HIV Risk

Black women continue to be disproportionately affected by the human immunodeficiency virus (HIV) that causes AIDS. To theorize additional approaches to HIV prevention targeting Black women, this study explores how social determinants related to sexual oppression, poverty, racial segregation, and mass incarceration of Blacks place Black women at increased risk of HIV exposure. The role of other risk factors such as sexual exploitation of the Black female body, poverty, residential racial segregation, and the mass incarceration of Black men are also explored. The study concludes with an examination of how these social determinants might be used to inform prevention approaches to help reduce HIV transmissions among Black women.

Infants with human immunodeficiency virus exposure or infection in the pediatric intensive care unit*

Infants with human immunodeficiency virus exposure or infection in the pediatric intensive care unit*

The New Invincibles: HIV Screening among Older Adults in the U.S

BackgroundThirteen percent of the U.S. population is ages 65 and older, a number projected to reach 20% by 2030. By 2015, 50% of Human Immunodeficiency Virus (HIV)-infected individuals in the U.S. are expected to be ages 50 and older. Current Centers for Disease Control and Prevention guidelines recommend “opt-out” HIV screening for individuals ages 13–64. The purpose of this study was to assess the occurrence and barriers to HIV screening in older adults, and to evaluate the rationale for expanding routine HIV screening to this population.MethodsThe study used 2009 National Health Interview Survey (NHIS) data. A total of 12,366 (unweighted) adults, ages 50 and older, participated in the adult section of the NHIS and answered questions on the HIV/AIDS, Sexually Transmitted Diseases, and Tuberculosis components. Associations between HIV screening, socio-demographic variables, and knowledge of HIV-related disease were examined using logistic regression models.ResultsThe HIV screening rate within this population was 25.4%. Race had no statistically significant effect. Low risk perception of HIV exposure (84.1%) accounted for low likelihood of planned screening (3.5%) within 12 months post survey. A routine medical check-up was the single most common reason for HIV screening (37.6%), with only about half (52.7%) of the tests suggested by a health care provider.ConclusionIt is imperative that practices and policies are developed and implemented to increase HIV awareness and screening in the older adult population. Increased health care provider awareness of the importance of HIV screening, especially for those 65 and older, is critical. Health policies and clinical guidelines should be revised to promote and support screening of all adults.

Criminalisation and Moral Responsibility for the Sexual Transmission of HIV

The essay that follows is an effort to take on a narrow but important question in a serious, though limited, way. The question is whether there is a MORAL case for lifting primary responsibility for Human immunodeficiency virus (HIV) prevention from the shoulders of those who know they are infected. The question is important because, for many people, it feels so obviously right to require those with HIV to accept this responsibility that punishing them as criminals if they fail to do so seems a natural, logical and entirely fair next step. As far as we can tell, objections to HIV exposure or transmission laws to date have rested on practical, rather than moral concerns. We will ask whether there is a good moral case to be made against criminalisation.There are two important things we will not do. We will not address the use of criminal law to deter or punish people who deliberately expose others to HIV with the aim of causing harm or with callous disregard of a significant risk of transmission. Like other commentators, we regard trying to harm others as wrongful and subject to prosecution regardless of the weapon used; our only concern in such a case, from the HIV perspective, is that a defendant not be punished more harshly only because the chosen weapon was the virus3 The second thing we will not do is attempt a moral analysis that is culturally comprehensive. The people of the world have developed many powerful systems of moral thought. We investigate our moral question within just one, the Western tradition of deontological ethics and liberal political philosophy. Our purpose is not, ultimately, to define for all people and all places a morality of HIV exposure, but to test whether the case for assigning primary moral responsibility for HIV to the person infected is as strong as it is assumed to be.

Correlates of Hepatitis B Virus and HIV Knowledge Among Gay and Bisexual Homeless Young Adults in Hollywood

Homeless gay and bisexual (G/B) young men have multiple risk factors that increase their risk of contracting hepatitis B virus (HBV) and human immunodeficiency virus (HIV). This study used baseline information from structured instruments to assess correlates of knowledge to HIV and HBV infection from 267 young (18-39 year old) G/B active methamphetamine, cocaine, and crack-using homeless men enrolled in a longitudinal trial. The study is designed to reduce drug use and improve knowledge of hepatitis and HIV/AIDS in a community center in Hollywood, California. Regression modeling revealed that previous hepatitis education delivered to G/B men was associated with higher levels of HIV/AIDS and hepatitis knowledge. Moreover, higher HIV/AIDS knowledge was associated with combining sex and drinking alcohol. Associations with hepatitis B knowledge was found among G/B men who were engaging in sex while under the influence of marijuana, who were receiving support from non-drug users, and who had been homeless in the last 4 months. Although being informed about HIV/AIDS and hepatitis did not preclude risky sexual and drug use behavior, knowledge about the dangers of concurrent sex with substance use is important. As higher levels of knowledge of hepatitis was associated with more moderate drug use, early access to testing and teaching harm reduction strategies remain critical to reduce exposure and infection of HBV and HIV in this population.

HIV‐1 alters neural and glial progenitor cell dynamics in the central nervous system: Coordinated response to opiates during maturation

HIV-associated neurocognitive disorders (HANDs) are common sequelae of human immunodeficiency virus (HIV) infection, even when viral titers are well controlled by antiretroviral therapy. Evidence in patients and animal models suggests that neurologic deficits are increased during chronic opiate exposure. We have hypothesized that central nervous system (CNS) progenitor cells in both adult and developing CNS are affected by HIV infection and that opiates exacerbate these effects. To examine this question, neural progenitors were exposed to HIV-1 Tat(1-86) in the developing brain of inducible transgenic mice and in vitro. We examined whether Tat affected the proliferation or balance of progenitor populations expressing nestin, Sox2, and Olig2. Disease relevance was further tested by exposing human-derived progenitors to supernatant from HIV-1 infected monocytes. Studies concentrated on striatum, a region preferentially targeted by HIV and opiates. Results were similar among experimental paradigms. Tat or HIV exposure reduced the proliferation of undifferentiated (Sox2(+)) progenitors and oligodendroglial (Olig2(+)) progenitors. Coexposure to morphine exacerbated the effects of Tat or HIV-1(SF162) supernatant, but partially reversed HIV-1(IIIB) supernatant effects. Populations of Sox2(+) and Olig2(+) cells were also reduced by Tat exposure, although progenitor survival was unaffected. In rare instances, p24 immunolabeling was detected in viable human progenitors by confocal imaging. The vulnerability of progenitors is likely to distort the dynamic balance among neuron/glial populations as the brain matures, perhaps contributing to reports that neurologic disease is especially prevalent in pediatric HIV patients. Pediatric disease is atypical in developed regions but remains a serious concern in resource-limited areas where infection occurs commonly at birth and through breast feeding.

Has highly active antiretroviral therapy increased the time to seroreversion in HIV exposed but uninfected children?

Since the introduction of highly active antiretroviral therapy (HAART) for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in pregnancy in the United States, the time of seroreversion in infants born to HIV-infected mothers has not been documented. The objective of this study was to determine the timing of clearance of HIV antibodies and to identify any associated biological and clinical factors. A retrospective analysis of infants who remained uninfected after perinatal HIV exposure was performed. Infant and maternal medical records from January 2000 to December 2007 were reviewed and the time of seroreversion was estimated using methods for censored survival data. In total, 744 infants were included in the study, with prenatal data available for 551 mothers. The median age of seroreversion was 13.9 months, and 14% of infants remained seropositive after 18 months, 4.3% after 21 months, and 1.2% after 24 months. Earlier age of seroreversion was associated with higher immunoglobulin G (IgG) levels at 3-7 months of age (P = .0029) and a higher rate of IgG change over the next 6 months of life (P = .003). Infants born by vaginal delivery were more likely to serorevert at a younger age (P = .0052), and maternal exposure to protease inhibitors was associated with a later age of seroreversion (P = .026). Clearance of HIV antibodies in uninfected infants was found to occur at a later age than has been previously reported. Fourteen percent of the infants had persistence of HIV antibodies at or beyond 18 months of age.