Prevention of the sexual transmission of HIV-1: preparing for success

There are four opportunities for HIV prevention: before exposure, at the moment of exposure, immediately after exposure, and as secondary prevention focused on infected subjects. Until recently, most resources have been directed toward behavioral strategies aimed at preventing exposure entirely. Recognizing that these strategies are not enough to contain the epidemic, investigators are turning their attention to post-exposure prevention opportunities. There is increasing focus on the use of ART–either systemic or topical (microbicides)–to prevent infection at the moment of exposure. Likewise, there is growing evidence that ART treatment of infected people could serve as prevention as well. A number of ongoing clinical trials will shed some light on the potential of these approaches. Above all, prevention of HIV requires decision-makers to focus resources on strategies that are most effective. Finally, treatment of HIV and prevention of HIV must be considered and deployed together

Impact of early-stage HIV transmission on treatment as prevention

Timely HIV treatment improves health (1) and reduces transmission (2). These individual- level benefits of HIV treatment for both clinical and preventive purposes are well established, but several questions remain about the population-level impact of HIV treatment as prevention (3). In PNAS, Eaton and Hallett (4) use a mathematical model to address one such question: Does the proportion of transmission during early HIV infection affect the impact of HIV treatment on HIV incidence

Advances in HIV Prevention for Serodiscordant Couples

Serodiscordant couples play an important role in maintaining the global HIV epidemic. This review summarizes biobehavioral and biomedical HIV prevention options for serodiscordant couples focusing on advances in 2013 and 2014, including World Health Organization guidelines and best-evidence for couples counseling, couples-based interventions, and the use of antiviral agents for prevention. In the past few years marked advances have been made in HIV prevention for serodiscordant couples and numerous ongoing studies are continuously expanding HIV prevention tools, especially in the area of pre-exposure prophylaxis. Uptake and adherence to antiviral therapy remains a key challenge. Additional research is needed to develop evidence-based interventions for couples, and especially for male-male couples. Randomized trials have demonstrated the prevention benefits of antiretroviral-based approaches among serodiscordant couples; however, residual transmission observed in recognized serodiscordant couples represents an important and resolvable challenge in HIV prevention

Treatment to Prevent Transmission of HIV‐1

Antiretroviral agents (ART) have the potential to prevent HIV transmission by reducing the concentration of HIV in blood and genital secretions. Indeed, mathematical models with favorable assumptions suggest the potential of ART to stop the spread of HIV. Empirical results from ecological and population based studies, and several short term observational studies involving HIV discordant heterosexual couples suggest that ART reduces HIV transmission. A multinational randomized controlled trial (NIH NPTN052) also examining the reliability and durability of ART as prevention in HIV discordant couples is underway. The latter and other studies also consider sexual risk taking behavior, and transmission of HIV resistant variants when ART is used as prevention. Early HIV detection and treatment (“test and treat”) are being considered as an important prevention strategy. In this article, we review the data supporting the use of ART to prevent HIV transmission, and critically examine the public health implications of this strategy

Effects of human serum on bacterial competition with neutrophils for molecular oxygen.

A dialyzable factor(s) in human serum is known to stimulate gonococcal oxygen consumption. Its effect on other human pathogens was investigated. A 10% serum solution increased peak O2 consumption for Escherichia coli and Staphylococcus aureus to 157% (P less than 0.05) and 199% (P less than 0.02), respectively, of their O2 consumption when suspended in Hanks balanced salt solution, compared with a 356% increase for Neisseria gonorrhoeae with serum. Dialyzed serum lacked stimulatory capacity. Bacteria, serum, and neutrophils are often incubated to evaluate neutrophil bactericidal activity. Samples of 10(8) N. gonorrhoeae, S. aureus, and E. coli turned resazurin colorless (anaerobic conditions, Eh less than -42 mV) after 7.4, 13.3, and 15.1 min, respectively. Because neutrophil formation of reactive oxygen intermediates requires ambient O2, the effect of live bacteria and serum on this process was explored. After 5 min of incubation of 10(8) N. gonorrhoeae or S. aureus in 10% normal or dialyzed serum, 10(5) neutrophils were added. Phorbol myristate acetate was then added to assure neutrophil stimulation, and luminol-dependent luminescence was measured. N. gonorrhoeae and S. aureus incubation in normal serum decreased peak LDL 91.7 and 88.6%, respectively, relative to incubation in dialyzed serum. A sample of 10(8) E. coli totally eliminated LDL. A sample of 10(8) E. coli incubated in Hanks balanced salt solution for 5 min also eliminated phorbol myristate acetate induced neutrophil H2O2 production. LDL inhibition increased in proportion to bacterial concentration and time of incubation and was prevented by inclusion of KCN. Increasing the concentration of neutrophils to 10(8) (1:1 particle-to-cell ratio) only partially reversed LDL inhibition. Re-aeration of the system allowed brief LDL which persisted only if KCN was added. Addition of KCN after bacterial incubation also permitted LDL, arguing against depletion of other factors from the media or accumulation of bacterially derived inhibitory substances. A dynamic competition for O2 occurs between bacteria and neutrophils. Serum stimulation of bacterial O2 utilization may contribute to virulence by increasing bacterial capacity to inhibit neutrophil function

Rebound of COVID-19 With Nirmatrelvir-Ritonavir Antiviral Therapy

In their article, Edelstein and colleagues provide the results of an observational study of virologic response in patients who received treatment with nirmatrelvir–ritonavir (N-R) versus those who received no COVID-19 therapy. The editorialists discuss the findings and emphasize the need for further consideration of the dosage, timing, and duration of treatment to inform optimal use of N-R

Chinaʼs syphilis epidemic: epidemiology, proximate determinants of spread, and control responses

China has experienced an increase in the incidence and prevalence of syphilis that is especially remarkable since this infection was virtually eradicated in the country 50 years ago. The purpose of this analysis is to provide an overview of recent literature on syphilis proximate determinants and potential public health responses

Recent key advances in human immunodeficiency virus medicine and implications for China

In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program

The Ethical Odyssey in Testing HIV Treatment as Prevention

Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HPTN 052, the multinational clinical trial addressing this issue that has profound public health implications

Effects of human serum on the growth and metabolism of Neisseria gonorrhoeae: an alternative view of serum.

Humans are the sole reservoir of Neisseria gonorrhoeae, an organism which undergoes a marked increase in metabolic rate after exposure to a low-molecular-weight, heat-stable component(s) of human serum. Further studies on the effect of serum on gonococcal metabolism were undertaken. Gonococcal broth (GCB) is commonly used for in vitro cultivation of gonococci. Gonococci suspended in GCB plus 10% serum exhibited oxygen consumption rates of 139% (P less than 0.01) and 456% (P less than 0.01) of those suspended in GCB or Hanks balanced salt solution, respectively. A twofold increase in growth rate also resulted from the addition of 10% serum to GCB. Gonococcal 14C-labeled adenine incorporation increased threefold with 10% serum supplementation of Hanks balanced salt solution. Dialysis of serum in 1,000-molecular-weight exclusion tubing removed the stimulatory factor(s). Neither correction of anion-cation concentrations altered by dialysis nor addition of substances of known importance to the metabolism of gonococci (i.e., lactate, pyruvate, cysteine, ATP, AMP, NADPH, amino acids, malate, and glutathione) to dialyzed serum reconstituted stimulatory capacity. The effect of serum on gonococcal glucose-catabolic pathways was measured by modified radiospirometry. An apparent threefold increase in Entner-Doudoroff and pentose phosphate pathway activities was induced by 10% serum, as was the increased shunting of glucose-derived glyceraldehyde-3-phosphate into these pathways. These metabolic changes did not allow specific identification of the serum stimulatory factor(s). Acetate, the major by-product of gonococcal glucose catabolism, inhibited gonococcal oxygen consumption as previously reported. A high-molecular-weight serum component, probably albumin, reversed acetate-mediated inhibition of gonococcal oxygen consumption, identifying a second mechanism by which serum increases gonococcal metabolism. These results suggest that supplementation of growth media with serum should be considered to provide N. gonorrhoeae with conditions more consistent with its normal environment