The Clinical Spectrum of HIV Infections: Implications for Public Policy

The term acquired immunodeficiency syndrome (AIDS) is a definition developed by the Centers for Disease Control to explain the epidemic of immunosuppression first seen in the United States among gay and bisexual men and intravenous drug users in the early 1980s. It is now known that the human immunodeficiency virus (HIV) is the necessary agent for the compromise of the immune system which results in AIDS; however, there is a wide range of manifestations associated with HIV infection. Individuals with AIDS tend to have severe opportunistic infections or malignancies, and the vast majority ofindividuals die within two years after the diagnosis. At least a fourth of the individuals with HIV infection in one study were found to remain asymptomatic after seven years of infection. Between the long period of asymptomatic infection and the development of life-threatening opportunistic infections, individuals may develop subacute manifestations of HIV infection. Some individuals may develop constitutional symptoms, without any other medical explanation. The clinical use of tests of immunologic function as well as newer tests that may describe the type of HIV infection, such as the serum antigen test, may enhance the ability of clinicians to give infected patients more specific information as to their prognosis. As newer therapies are developed, the utilization of newer diagnostic tests may allow for staging more rational treatment plans. The data suggesting increasing efficacy of Azidothymidine (AZT), as well as the development of newer chemotherapeutic agents, may lead to more widespread HIV testing in order to detect infection at early stages and intervene with specific therapies. Use of the test as a means of altering behavior remains controversial. The development of newer therapies is hindered by the need to avoid exposing HIV-infected individuals to agents that subsequently turn out to be harmful, such as HPA-23 and Suramin. But this must be balanced with the urgent need of individuals to try promising therapeutic agents. Preliminary data suggest that individuals who are treated with AZT at earlier stages of HIV infection may do better; thus, there may be a move in the future to treat people with AZT. The clinical dilemma will persist for some time to come, and the cost of care for individuals with AIDS and HIV infection will be extremely high. Although the illness is frequently fatal, it is most appropriate to be considerate of the individual\u27s desire to have more aggressive therapies, given the variability of HIV infection for each person and the fact that new therapeutic breakthroughs are being made every day

Immune Reconstitution in HIV-Infected Patients

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of potent antiretroviral therapies (ARTs), which have enabled sustained suppression of HIV replication and recovery of CD4 T cell counts. Knowledge of the function of CD4 T cells in immune reconstitution was derived from large clinical studies demonstrating that primary and secondary prophylaxis against infectious agents, such as Pneumocystis jirovecii (Pneumocystis carinii), Mycobacterium avium complex, cytomegalovirus, and other pathogens, can be discontinued safely once CD4 T cell counts have increased beyond pathogen-specific threshold levels (usually >200 CD4 T cells/mm3) for 3-6 months. The downside of immune reconstitution is an inflammatory syndrome occurring days to months after the start of ART, with outcomes ranging from minimal morbidity to fatal progression. This syndrome can be elicited by infectious and noninfectious antigens. Microbiologically, the possible pathogenic pathways involve recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infection. Specific antimicrobial therapy, nonsteroidal anti-inflammatory drugs, and/or steroids for managing immune reconstitution syndrome should be considere

Cognitive behavioral therapy for body image and self-care (CBT-BISC) in sexual minority men living with HIV: a randomized controlled trial

OBJECTIVE: Body image disturbance is a distressing and interfering problem among many sexual minority men living with HIV, and is associated with elevated depressive symptoms and poor HIV self-care (e.g., antiretroviral therapy [ART] nonadherence). The current study tested the preliminary efficacy of a newly created intervention: cognitive–behavioral therapy for body image and self-care (CBT-BISC) for this population. METHOD: The current study entailed a 2-arm randomized controlled trial (N = 44) comparing CBT-BISC to an enhanced treatment as usual (ETAU) condition. Analyses were conducted at 3 and 6 months after baseline. The primary outcome was body image disturbance (BDD-YBOCS), and secondary outcomes were ART adherence (electronically monitored via Wisepill), depressive symptoms (MADRS), and global functioning (GAF). RESULTS: At 3 months, the CBT-BISC condition showed substantial improvement in BDD-YBOCS (b = −13.6, SE = 2.7, 95% CI [−19.0, −8.3], p < .001; dppc2 = 2.39); MADRS (b = −4.9, SE = 2.8, 95% CI [−10.6, .70], p = .086; dppc2 = .87); ART adherence (b = 8.8, SE = 3.3, 95% CI [2.0, 15.6], p = .01; dppc2 = .94); and GAF (b = 12.3, SE = 3.2, 95% CI [6.1, 18.6], p < .001; dppc2 = 2.91) compared with the ETAU condition. Results were generally maintained, or improved, at 6 months; although, adherence findings were mixed depending on the calculation method. CONCLUSIONS: CBT-BISC shows preliminary efficacy in the integrated treatment of body image disturbance and HIV self-care behaviors among sexual minority men living with HIV. (APA PsycInfo Database Record (c) 2019 APA, all rights reserved)Funding from this project came from K23MH096647. Author time for Steven A. Safren was supported by K24DA040489 (formally K24MH094214). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. (K23MH096647; K24DA040489; K24MH094214)Accepted manuscrip

Pharmacy Adherence Measures to Assess Adherence to Antiretroviral Therapy: Review of the Literature and Implications for Treatment Monitoring

Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to AR

Formulating the Future Research Agenda for Postexposure Prophylaxis for HIV: Methodological Challenges and Potential Approaches

Background. During a World Health Organization-convened Guideline Development Group meeting, recommendations for postexposure prophylaxis (PEP) for human immunodeficiency virus were made and research gaps identified. Methods. We used the PEP clinical management pathway and the Grading of Evidence, Assessment, Development and Evaluation (GRADE) system as a framework to formulate future research questions, describe the most feasible study design, and identify potential biases. Results. Three key study design formats were identified to address 12 research questions: (1) survey- and interview-driven research to identify barriers to access to PEP and related clinical care; (2) establishment of a global PEP registry to generate data to inform the choice of an optimal PEP drug regimen, record drug toxicities arising from specific PEP regimens, and track follow-up and linkage to care (including transition from PEP to preexposure prophylaxis); and (3) randomized controlled trials to determine the optimal adherence promotion strategies necessary for successful outcomes following PEP. Conclusions.  Positioning key clinical and programmatic research questions within the GRADE framework facilitates the formulation of an evidence-based research agenda and future revisions of guideline

AIDS in America — Forgotten but Not Gone

Over the past decade, limited attention has been paid to the human immunodeficiency virus (HIV) epidemic in the United States. The global epidemic — particularly the epidemic in sub-Saharan Africa, where approximately two thirds of the world's population living with AIDS resides — has rightfully received most of the focus. Meanwhile, however, the prevalence of HIV infection within some U.S. populations now rivals that in some sub-Saharan African countries

Combination Therapy with Ciprofloxacin plus Azlocillin against Pseudomonas aeruginosa: Effect of Simultaneous versus Staggered Administration in an In Vitro Model of Infection

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum” compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal µ-lactam with ciprofloxacin against P. aeruginos

Human immunodeficiency virus type-1 episomal cDNA in semen

BACKGROUND: Episomal 2-long terminal repeat (LTR) HIV-1 cDNA, a by-product of HIV-1 infection, is used in clinical trials as a marker for ongoing viral replication. It would be useful to employ 2-LTR cDNA to monitor cryptic HIV-1 infection in the genital tract of men on antiretroviral therapy (ART) to predict the evolution of sexually transmissible drug-resistant HIV-1, but studies thus far have failed to detect this marker in semen. The objectives of this study were: 1) to use a technique that maximizes DNA recovery from HIV-1 infected white blood cells in semen to determine if episomal 2-LTR cDNA is detectable in semen of ART-naïve men with other evidence of genital tract HIV-1 infection, and 2) to compare levels of HIV-1 2-LTR cDNA, RNA, and proviral DNA in semen from HIV-1+ men on ART. RESULTS: Using a somatic cell DNA extraction technique, 2-LTR cDNA was detected by PCR/ELISA in 4 out of 8 semen samples from ART-naïve men selected for other signs of seminal HIV-1 infection (positive controls). Southern blot and DNA sequencing confirmed that the amplified sequences were HIV-1 2-LTR cDNA; copy numbers ranged from 55 to 504 copies/sample. Two semen samples from a cohort of 22 HIV-1-infected men on dual nucleoside therapy, one with and one without detectable seminal HIV-1 RNA, were 2-LTR cDNA positive (336 and 8,560 copies/sample). Following addition of indinavir to the therapy regimen, no semen samples from 21 men with controlled peripheral and seminal viral loads were 2-LTR cDNA positive at 1 and 6 month time points, despite the persistence of HIV-1 proviral DNA+ semen cells and seminal cytomegalovirus (CMV) shedding in some cases. However, one individual who failed indinavir therapy and later developed distinct protease inhibitor (PI) drug resistance mutations in semen, maintained elevated levels of HIV-1 RNA and 2-LTR cDNA in semen. CONCLUSION: 2-LTR HIV-1 cDNA is detectable in semen of HIV-1-infected men. Two men on ART had 2-LTR HIV-1 cDNA in semen, suggesting that this marker may prove to be useful to monitor HIV-1 infection in the genital tract of men on ART to predict the evolution of drug resistance mutations in semen

Urban Evolution: The Role of Water

The structure, function, and services of urban ecosystems evolve over time scales from seconds to centuries as Earth’s population grows, infrastructure ages, and sociopolitical values alter them. In order to systematically study changes over time, the concept of “urban evolution” was proposed. It allows urban planning, management, and restoration to move beyond reactive management to predictive management based on past observations of consistent patterns. Here, we define and review a glossary of core concepts for studying urban evolution, which includes the mechanisms of urban selective pressure and urban adaptation. Urban selective pressure is an environmental or societal driver contributing to urban adaptation. Urban adaptation is thesequential process by which an urban structure, function, or services becomes more fitted to its changing environment or human choices. The role of water is vital to driving urban evolution as demonstrated by historical changes in drainage, sewage flows, hydrologic pulses, and long-term chemistry. In the current paper, we show how hydrologic traits evolve across successive generations of urban ecosystems via shifts in selective pressures and adaptations over time. We explore multiple empirical examples including evolving: (1) urban drainage from stream burial to stormwater management; (2) sewage flows and water quality in response to wastewater treatment; (3) amplification of hydrologic pulses due to the interaction between urbanization and climate variability; and (4) salinization and alkalinization of fresh water due to human inputs and accelerated weathering. Finally, we propose a new conceptual model for the evolution of urban waters from the Industrial Revolution to the present day based on empirical trends and historical information. Ultimately, we propose that water itself is a critical driver of urban evolution that forces urban adaptation, which transforms the structure, function, and services of urban landscapes, waterways, and civilizations over time