Hidden costs: The ethics of cost-effectiveness analyses for health interventions in resource-limited settings

Cost-effectiveness analysis (CEA) is an increasingly appealing tool for evaluating and comparing health-related interventions in resource-limited settings. The goal is to inform decision-makers regarding the health benefits and associated costs of alternative interventions, helping guide allocation of limited resources by prioritizing interventions that offer the most health for the least money. Although only one component of a more complex decision-making process, CEAs influence the distribution of healthcare resources, directly influencing morbidity and mortality for the world’s most vulnerable populations. However, CEA-associated measures are frequently setting-specific valuations, and CEA outcomes may violate ethical principles of equity and distributive justice. We examine the assumptions and analytical tools used in CEAs that may conflict with societal values. We then evaluate contextual features unique to resource-limited settings, including the source of health-state utilities and disability weights; implications of CEA thresholds in light of economic uncertainty; and the role of external donors. Finally, we explore opportunities to help align interpretation of CEA outcomes with values and budgetary constraints in resource-limited settings. The ethical implications of CEAs in resource-limited settings are vast. It is imperative that CEA outcome summary measures and implementation thresholds adequately reflect societal values and ethical priorities in resource-limited settings

The Role of Acute and Early HIV Infection in the Sexual Transmission of HIV

Acute HIV infection (AHI), the earliest period after HIV acquisition, is only a few weeks in duration. In this brief period, the concentration of HIV in blood and genital secretions is extremely high, increasing the probability of HIV transmission. Although a substantial role of AHI in the sexual transmission of HIV is biologically plausible, the significance of AHI in the epidemiological spread of HIV remains uncertain

The HIV treatment cascade in acutely infected people: informing global guidelines

Acute and early HIV (AHI) is a pivotal time during HIV infection, yet there remain major shortfalls in diagnosis, linkage to care, and antiretroviral therapy (ART) initiation during AHI. We introduce an AHI-specific cascade, review recent evidence pertaining to the unique challenges of AHI, and discuss strategies for improving individual and public health outcomes

Tenofovir-Associated Nephrotoxicity in Two HIV-Infected Adolescent Males

We report two cases of tenofovir (TDF)-associated nephrotoxicity in perinatally HIV-infected adolescents. The first case, a 16-year-old African American male with an absolute CD4+ cell count of 314 cells/mm3, presented with an abrupt rise in serum creatinine leading to irreversible renal failure while on TDF-containing highly active antiretroviral therapy (HAART). While the patient had evidence of underlying kidney disease, the timing of his renal failure indicates that TDF played a central role. The second case, a 16-year-old African-American male with an absolute CD4+ cell count of 895 cells/mm3, presented with rickets and hypophosphatemia while receiving TDF-based HAART. To our knowledge, these cases represent the first reports of TDF-associated irreversible renal failure and rickets in pediatric patients. We believe these cases highlight important and potentially irreversible side effects of this agent and emphasize the need for further studies of the renal safety of TDF in pediatric patients

A preoperative personalized risk assessment calculator for elderly ovarian cancer patients undergoing primary cytoreductive surgery

Cytoreductive surgery for ovarian cancer has higher rates of postoperative complication than neoadjuvant chemotherapy followed by surgery. If patients at high risk of postoperative complication were identified preoperatively, primary therapy could be tailored. Our objective was to develop a predictive model to estimate the risk of major postoperative complication after primary cytoreductive surgery among elderly ovarian cancer patients

Cost-Effectiveness of Laparoscopic Hysterectomy With Morcellation Compared With Abdominal Hysterectomy for Presumed Myomas

Hysterectomy for presumed leiomyomata is one of the most common surgical procedures performed in non-pregnant women in the United States. Laparoscopic hysterectomy (LH) with morcellation is an appealing alternative to abdominal hysterectomy (AH), but may result in dissemination of malignant cells and worse outcomes in the setting of an occult leiomyosarcoma. We sought to evaluate the cost-effectiveness of LH versus AH

The Detection and Management of Early HIV Infection: A Clinical and Public Health Emergency

This review considers the detection and management of early HIV infection (EHI), defined here as the first 6 months of infection. This phase is clinically important because a reservoir of infected cells formed in the individual renders HIV incurable, and the magnitude of viremia at the end of this period predicts the natural history of disease. Epidemiologically, it is critical because the very high viral load that typically accompanies early infection also makes infected individuals maximally contagious to their sexual partners. Future efforts to prevent HIV transmission with expanded testing and treatment may be compromised by elevated transmission risk earlier in the course of HIV infection, although the extent of this impact is yet unknown. Treatment as prevention efforts will nevertheless need to develop strategies to address testing, linkage to care, and treatment of EHI. Cost-effective and efficient identification of more persons with early HIV will depend on advancements in diagnostic technology and strengthened symptom-based screening strategies. Treatment for persons with EHI must balance individual health benefits and reduction of the risk of onward viral transmission. An increasing body of evidence supports the use of immediate antiretroviral therapy to treat EHI to maintain CD4 count and functionality, limit the size of the HIV reservoir, and reduce the risk of onward viral transmission. Although we can anticipate considerable challenges in identifying and linking to care persons in the earliest phases of HIV infection, there are many reasons to pursue this strategy

Incorporating Acute HIV Screening into Routine HIV Testing at Sexually Transmitted Infection Clinics, and HIV Testing and Counseling Centers in Lilongwe, Malawi

Background and Objectives:Integrating acute HIV-infection (AHI) testing into clinical settings is critical to prevent transmission, and realize potential treatment-as-prevention benefits. We evaluated acceptability of AHI testing and compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV testing and counseling (HTC) clinics in Lilongwe, Malawi.Methods:We conducted HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI was defined as positive RNA and negative/discordant rapid antibody tests. We evaluated demographic, behavioral, and transmission-risk differences between STI and HTC patients and assessed performance of a risk-score for targeted screening.Results:Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)–a 0.9% case-identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs 0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25% (15/59) had VL ≥10,000,000 copies per milliliter. Median VL was higher at STI (1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among persons with AHI, those tested at STI clinics were more likely to report genital sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The risk score algorithm performed well in identifying persons with AHI at HTC clinics (sensitivity = 73%, specificity = 89%).Conclusions:The majority of patients consented to AHI testing. AHI prevalence was substantially higher in STI clinics than HTC clinics. Remarkably high VLs and concomitant genital scores demonstrate the potential for transmission. Universal AHI screening at STI clinics, and targeted screening at HTC centers, should be considered

Sustained Sexual Behavior Change after Acute HIV Diagnosis in Malawi

Background Identification of acute HIV infection (AHI) allows for important opportunities for HIV prevention through behavior change and biomedical intervention. Here, we evaluate changes in sexual risk behaviors among persons with AHI enrolled in a combined behavioral and biomedical intervention designed to reduce onward transmission of HIV. Methods Participants were randomized to standard HIV counseling, a multisession behavioral intervention, or a multisession behavioral intervention plus antiretrovirals. Sexual behaviors were assessed periodically over 1 year. Results Four weeks after diagnosis, the predicted probability of reporting multiple sexual partners decreased from 24% to 9%, and the probability of reporting unprotected sex decreased from 71% to 27%. These declines in sexual risk behaviors were sustained over follow-up irrespective of study arm. Conclusions Diagnosis of AHI alone may be sufficient to achieve immediate and sustained behavior change during this highly infectious period

Human Immunodeficiency Virus (HIV)-1 Transmission among Persons with Acute HIV-1 Infection in Malawi: Demographic, Behavioral, and Phylogenetic Relationships

Background: Understanding sexual networks involving acute human immunodeficiency virus (HIV)-1 infections (AHI) may lead to prevention opportunities to mitigate high rates of onward transmission. We evaluated HIV-1 phylogenetic and behavioral characteristics among persons with AHI and their referred partners. Methods: Between 2012 and 2014, 46 persons with AHI in Malawi participated in a combined behavioral and biomedical intervention. Participants referred sexual partners by passive referral. Demographics and sexual behaviors were collected through interviews and HIV-1 genetic relationships were assessed with phylogenetics. Results: Among 45 AHI participants with HIV-1 sequences, none was phylogenetically-linked with another AHI index. There were 19 (42%) AHI participants who referred a single partner that returned for testing. Most partners (n = 17) were HIV-infected, with 15 (88%) presenting with an established infection. There were 14 index-partner pairs that had sequences available; 13 (93%) pairs were phylogenetically-linked dyads. The AHI index was female in 7/13 (54%) dyads. Age-disparate relationships among dyads were common (≥5-year age difference in 67% of dyads), including 3/6 dyads involving a male index and a younger woman. Index participants with a referred partner were more likely to report no casual partners and to be living with their current partner than participants not in dyads. Conclusions: Passive-partner referral successfully identified partners with genetically-similar HIV infections - the likely source of infection - but only 40% of index cases referred partners who presented for HIV-1 testing. Future work evaluating assisted partner notification may help reach susceptible partners or more people with untreated HIV-1 infections connected to acute transmission. Clinical Trials Registration: NCT01450189