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The current opioid crisis in the United States has emerged from higher demand for and prescribing of opioids as chronic pain medication, leading to massive diversion into illicit markets. A peculiar tragedy is that many health professionals prescribed opioids in a misguided response to legitimate concerns that pain was undertreated. The crisis grew not only from overprescribing, but also from other sources, including insufficient research into nonopioid pain management, ethical lapses in corporate marketing, historical stigmas directed against people who use drugs, and failures to deploy evidence-based therapies for opioid addiction and to comprehend the limitations of supply-side regulatory approaches. Restricting opioid prescribing perversely accelerated narco-trafficking of heroin and fentanyl with consequent increases in opioid overdose mortality As injection replaced oral consumption, outbreaks of hepatitis B and C virus and human immunodeficiency virus infections have resulted. This viewpoint explores the origins of the crisis and directions needed for effective mitigation. [ABSTRACT FROM AUTHOR]

Background: Within the context of a cluster randomized prevention of mother-to-child HIV transmission (PMTCT) trial, we evaluated the impact of disclosure on selected PMTCT continuum of care measures. Methods: In 12 rural matched-pair clinics randomly assigned to an intervention package versus standard-ofcare, we enrolled 372 HIV-infected pregnant women from April 2013 to March 2014. This secondary analysis included 327 (87.9%) women with unknown HIV status or who were treatment naïve at presentation to antenatal care. We employed mixed effects logistic regression to estimate impact of disclosure on facility delivery and postpartum retention in HIV care at 6 and 12 weeks. Results: Fully 86.5% (283/327) of women disclosed their HIV status to their partner, more in the trial intervention arm (OR 3.17, 95% CI 1.39-7.23). Adjusting for intervention arm, maternal age, education and employment, women who disclosed were more likely to deliver at a health facility (OR 2.73, 95%CI 1.11-6.72). Participants who disclosed also had a trend towards being retained in care at 6 and 12 weeks' postpartum (OR 2.72, 95% CI 0.79-9.41 and 2.46, 95% CI 0.70-8.63, respectively). Conclusions: HIV status disclosure at 6 weeks' postpartum was positively associated with facility-based delivery, but not with early postpartum retention. Facilitating HIV status disclosure to partners can increase utilization of facility obstetric services. [ABSTRACT FROM AUTHOR]

More than half a million Americans became newly infected with human immunodeficiency virus (HIV) in the first decade of the new millennium. The domestic epidemic has had the heaviest impact on men who have sex with men and persons from racial and ethnic minority populations, particularly black persons. For example, black men who have sex with men represent <1% of the US population but 25% of new HIV infections, according to Centers for Disease Control and Prevention estimates published in 2008. Although black and Hispanic women constitute 24% of all US women, they accounted for 82% of HIV infections among women in 2005, according to data from 33 states with confidential name-based reporting. There is a nearly 23-fold higher rate of AIDS diagnoses among black women (45.5 diagnoses per 100,000 women) and a nearly 6-fold higher rate among Hispanic women (11.2 diagnoses per 100,000 women), compared with the rate among white women (2.0 diagnoses per 100,000 women). Investigators from the HIV Prevention Trials Network, a National Institutes of Health-sponsored collaborative clinical trials group, have crafted a domestic research agenda with community input. Two new domestic studies are in progress (2009), and a community-based clinical trial feasibility effort is in development (2010 start date). These studies focus on outreach, testing, and treatment of infected persons as a backbone for prevention of HIV infection. Reaching persons not receiving health messages and services with novel approaches to both prevention and treatment is an essential priority for control of HIV infection in the United States; our research is designed to guide the best approaches and assess the impact of bridging treatment and prevention. [ABSTRACT FROM AUTHOR]

In many programs providing antiretroviral therapy (ART), clinicians report substantial patient attrition; however, there are no consensus criteria for defining patient loss to follow-up (LTFU). Data on a multisite human immunodeficiency virus (HIV) treatment cohort in Lusaka, Zambia, were used to determine an empirical “days-late” definition of LTFU among patients on ART. Cohort members were classified as either “in care” or LTFU as of December 31, 2007, according to a range of days-late intervals. The authors then looked forward in the database to determine which patients actually returned to care at any point over the following year. The interval that best minimized LTFU misclassification was described as “best-performing.” Overall, 33,704 HIV-infected adults on ART were included. Nearly one-third (n = 10,196) were at least 1 day late for an appointment. The best-performing LTFU definition was 56 days after a missed visit, which had a sensitivity of 84.1% (95% confidence interval (CI): 83.2, 85.0), specificity of 97.5% (95% CI: 97.3, 97.7), and misclassification of 5.1% (95% CI: 4.8, 5.3). The 60-day threshold performed similarly well, with only a marginal difference (<0.1%) in misclassification. This analysis suggests that ≥60 days since the last appointment is a reasonable definition of LTFU. Standardization to empirically derived definitions of LTFU will permit more reliable comparisons within and across programs. [ABSTRACT FROM PUBLISHER]

The article focuses on a study conducted by the authors related to the Use of Pharmacokinetic Data in Novel Analyses to Determine the Effect of topical Microbicides as Preexposure Prophylaxis Against HIV Infection. Tocpis disucssed include the VOICE trial failing to indicate the affectivity of topical tenofovir, oral tenofovir to protect women against HIV, high incidence of HIV infection among sub-Saharan African regions, and other studies to demonstrate product efficacy and effectiveness.

Background. Rates of perinatal human immunodeficiency virus (HIV) transmission are higher among HIV infected mothers with more advanced disease, but effects of maternal disease on HIV-uninfected offspring are unclear. We investigated the hypothesis that the severity of HIV disease and immune dysfunction among mothers is associated with increased morbidity and mortality among their uninfected infants. Methods. In a birth cohort of 20 HIV-uninfected infants born to HIV-infected mothers in Lusaka, Zambia, e investigated associations between markers of more advanced maternal HIV disease and child mortality, hospital admissions, and infant weight through 4 months of age. Results. Mortality in the cohort of uninfected infants was 4.6% (95% confidence interval [CI], 2.8-6.3) through 4 months of age. Infants of mothers with CD4+ T cell counts of <350 cells/mL were more likely to die (hazard ratio [HR], 2.87; 95% CI, 1.03-8.03) and were more likely to be hospitalized (HR, 2.28; 95% CI, 1.17- 4.45), after adjusting for other factors, including maternal death and low birth weight. The most common cause of infant death and hospitalization was pneumonia and/or sepsis. A maternal viral load of 1100,000 copies/mL was associated with significantly lower child weight through 4 months of age. Conclusion. Children born to HIV-infected mothers with advanced disease who escaped perinatal or early breastfeeding-related HIV infection are nonetheless at high risk of mortality and morbidity during the first few months of life. HIV-related immunosuppression appears to have adverse consequences for the health of infants, in addition to risks of vertical transmission. [ABSTRACT FROM AUTHOR]

Seventeen women who were persistently uninfected by human immunodeficiency virus type 1 (HIV-1), despite repeated sexual exposure, and 12 of their HIV-positive male partners were studied for antiviral correlates of non-transmission. Thirteen women had > or = 1 immune response in the form of CD8 cell noncytotoxic HIV-1 suppressive activity, proliferative CD4 cell response to HIV antigens, CD8 cell production of macrophage inflammatory protein-1 beta, or ELISPOT assay for HIV-1-specific interferon-gamma secretion. The male HIV-positive partners without AIDS had extremely high CD8 cell counts. All 8 male partners evaluated showed CD8 cell-related cytotoxic HIV suppressive activity. Reduced CD4 cell susceptibility to infection, neutralizing antibody, single-cell cytokine production, and local antibody in the women played no apparent protective role. These observations suggest that the primary protective factor is CD8 cell activity in both the HIV-positive donor and the HIV-negative partner. These findings have substantial implications for vaccine development. [ABSTRACT FROM AUTHOR]

Presents a study which examined human immunodeficiency virus infection associated with ectopy among adolescent girls. Background on ectopy; Characteristics of subjects; Methods; Results.

In many cities, human immunodeficiency virus (HIV)-1 seroprevalence among drug injectors stabilizes at 30–70% for many years without secondary outbreaks that increase seroprevalence by 15% or more. The authors considered how HIV-1 incidence can remain moderate at seroprevalence levels that would give maximum incidence. Previously suggested answers include behavioral risk reduction and network saturation within high-risk subgroups. Among 767 drug injectors studied in 1991–1993, during a period of stable high seroprevalence in New York City, risk behaviors remained common, and networks were far from saturated. The authors suggest a different network-based mechanism: in stable high-prevalence situations, the relatively small sizes of subnetworks of linked seronegatives (within larger networks containing both infected and uninfected persons) may limit infectious outbreaks. Any primary infection outbreak would probably be limited to members of connected subcomponents of seronegatives, and the largest such subcomponent in the study contained only 18 members (of 415 seronegatives). Research and mathematical modeling should study conditions that may affect the size and stability of subcomponents of seronegatives. Finally, if the existence of small, connected components of seronegatives prevents secondary outbreaks, this protection may weaken, and vulnerability to new outbreaks increase, if HIV-1 seroprevalence falls. Thus, in situations of declining prevalence, prevention programs should be maintained or strengthened. Am J Epidemiol 2000;152:913–22. [ABSTRACT FROM PUBLISHER]

The article reflects on the benefits of antiretroviral therapy (ART) in Africa. Topics of discussion included were transformational public health efforts in modern history with the U.S. President's Emergency Plan for AIDS Relief, the Global Fund to Fight AIDS, Tuberculosis and Malaria and effort to prevent human immunodeficiency virus (HIV) infection with ART-based care to infected persons. It also discusses the role of the South African government in HIV-related morbidity and mortality.