HIV testing of pregnant women: an ethical analysis

Recent global advances in available technology to prevent mother-to-child HIV transmission necessitate a rethinking of contemporary and previous ethical debates on HIV testing as a means to preventing vertical transmission. In this paper, we will provide an ethical analysis of HIV-testing strategies of pregnant women. First, we argue that provider-initiated opt-out HIV testing seems to be the most effective HIV test strategy. The flip-side of an opt-out strategy is that it may end up as involuntary testing in a clinical setting. We analyse this ethical puzzle from a novel perspective, taking into account the moral importance of certain hypothetical preferences of the child, as well as the moral importance of certain actual preferences of the mother. Finally, we balance the conflicting concerns and try to arrive at an ethically sound solution to this dilemma. Our aim is to introduce a novel perspective from which to analyse testing strategies, and to explore the implications and possible benefits of our proposal. The conclusion from our analysis is that policies that recommend provider-initiated opt-out HIV testing of pregnant mothers, with a risk of becoming involuntary testing in a clinical setting, are acceptable. The rationale behind this is that the increased availability of very effective and inexpensive life-saving drugs makes the ethical problems raised by the possible intrusiveness of HIV testing less important than the child's hypothetical preferences to be born healthy. Health care providers, therefore, have a duty to offer both opt-out HIV testing and available PMTCT (preventing mother-to-child transmission) interventions.     

A mathematical model of comprehensive test-and-treat services and HIV incidence among men who have sex with men in the United States

Background

Early diagnosis and treatment of HIV infection and suppression of viral load are potentially powerful interventions for reducing HIV incidence. A test-and-treat strategy may have long-term effects on the epidemic among urban men who have sex with men (MSM) in the United States and may achieve the 5-year goals of the 2010 National AIDS Strategy that include: 1) lowering to 25% the annual number of new infections, 2) reducing by 30% the HIV transmission rate, 3) increasing to 90% the proportion of persons living with HIV infection who know their HIV status, 4) increasing to 85% the proportion of newly diagnosed patients linked to clinical care, and 5) increasing by 20% the proportion of HIV-infected MSM with an undetectable HIV RNA viral load.

Methods and Findings

We constructed a dynamic compartmental model among MSM in an urban population (based on New York City) that projects new HIV infections over time. We compared the cumulative number of HIV infections in 20 years, assuming current annual testing rate and treatment practices, with new infections after improvements in the annual HIV testing rate, notification of test results, linkage to care, initiation of antiretroviral therapy (ART) and viral load suppression. We also assessed whether five of the national HIV prevention goals could be met by the year 2015. Over a 20-year period, improvements in test-and-treat practice decreased the cumulative number of new infections by a predicted 39.3% to 69.1% in the urban population based on New York City. Institution of intermediate improvements in services would be predicted to meet at least four of the five goals of the National HIV/AIDS Strategy by the 2015 target.

Conclusions

Improving the five components of a test-and-treat strategy could substantially reduce HIV incidence among urban MSM, and meet most of the five goals of the National HIV/AIDS Strategy.     

ETHICS OF MANDATORY PREMARITAL HIV TESTING IN AFRICA: THE CASE OF GOMA, DEMOCRATIC REPUBLIC OF CONGO

Despite decades of prevention efforts, millions of persons worldwide continue to become infected by the human immunodeficiency virus (HIV) every year. This urgent problem of global epidemic control has recently lead to significant changes in HIV testing policies. Provider-initiated approaches to HIV testing have been embraced by the Centers for Disease Control and Prevention and the World Health Organization, such as those that routinely inform persons that they will be tested for HIV unless they explicitly refuse ('opt out'). While these policies appear to increase uptake of testing, they raise a number of ethical concerns that have been debated in journals and at international AIDS conferences. However, one special form of 'provider-initiated' testing is being practiced and promoted in various parts of the world, and has advocates within international health agencies, but has received little attention in the bioethical literature: mandatory premarital HIV testing. This article analyses some of the key ethical issues related to mandatory premarital HIV testing in resource-poor settings with generalized HIV epidemics. We will first briefly mention some mandatory HIV premarital testing proposals, policies and practices worldwide, and offer a number of conceptual and factual distinctions to help distinguish different types of mandatory testing policies. Using premarital testing in Goma (Democratic Republic of Congo) as a point of departure, we will use influential public health ethics principles to evaluate different forms of mandatory testing. We conclude by making concrete recommendations concerning the place of mandatory premarital testing in the struggle against HIV/AIDS.     

Design of Viral Dynamic Studies for Efficiently Assessing Potency of Anti‐HIV Therapies in AIDS Clinical Trials

The study of HIV dynamics is one of the most important developments in recent AIDS research. It greatly improves our understanding of the pathogenesis of HIV infection. Recently it has been proposed to use HIV dynamics to evaluate the efficacy of antiviral treatments. Currently a large number of AIDS clinical trials on HIV dynamics are in development worldwide. However, many design issues that arise from HIV dynamic studies have not been addressed. In this paper, we study these problems using intensive Monte Carlo simulations and analytic methods. We evaluate a finite number of feasible candidate designs, which are currently used and proposed in AIDS clinical trials from different perspectives. We compare the viral dynamic marker and classical viral load change markers in terms of power for identifying treatment difference, asymptotic relative efficiency, and sensitivity. Finally we propose some useful suggestions for practitioners based on our results.     

Guidelines for the Control of Human Immunodeficiency Virus Infection in Adolescents

Although adolescents account for only 0.4% of reported cases of the acquired immunodeficiency syndrome (AIDS) in the United States, they are sexually active and, therefore, at risk of acquiring human immunodeficiency virus (HIV) infection. To address issues of HIV control in adolescents, we developed guidelines that emphasize education and medical care and deemphasize antibody testing. For adolescents known to be infected with HIV, we recommend no restrictions on access to educational or treatment programs except when their health providers recommend such restrictions to protect them from exposure to opportunistic infections. For adolescents of unknown antibody status with a possible previous exposure to HIV, we recommend that as long as the incidence of HIV infection and clinical AIDS remains low, there should be no restrictions on residential placements and no routine antibody testing.     

Is human immunodeficiency virus/acquired immunodeficiency syndrome decreasing among Brazilian injection drug users? Recent findings and how to interpret them

We briefly review findings from Brazilian settings where the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic among injection drug users (IDUs) seems to be decreasing, highlighting recent findings from Rio de Janeiro and discussing methodological alternatives. Former analyses using serologic testing algorithm for recent HIV seroconversion have shown that HIV incidence has been low in IDUs recruited by two different surveys carried out in Rio, where low injection frequencies and infection rates have been found among new injectors. The proportion of AIDS cases among IDUs in Rio has been fairly modest, compared to S?o Paulo and especially to the southernmost states. Notwithstanding, the interpretation of findings from serial surveys constitutes a challenge, magnified in the assessment of HIV spread among IDUs due to the dynamic nature of the drug scenes and limitations of sampling strategies targeting hard-to-reach populations. Assessment of epidemic trends may profit from the triangulation of data, but cannot avert biases associated with sampling errors. Efforts should be made to triangulate data from different sources, besides exploring specific studies from different perspectives. In an attempt to further assess the observed trends, we carried out original analyses using data from Brazilian AIDS databank.     

Koch's postulates and the etiology of AIDS: an historical perspective.

This paper examines the debate over the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS) from an historical perspective. The changing criteria for proving the link between putative pathological agents and diseases are discussed, beginning with Robert Koch's research on anthrax in the late nineteenth century. Various versions of 'Koch's postulates' are analyzed in relation to the necessity and sufficiency arguments of logical reasoning. In addition, alterations to Koch's postulates are delineated, specifically those required by the discovery of rickettsiae and viruses in the early twentieth century and by the immunological testing developed after mid-century to demonstrate the links between elusive viral agents and two diseases, hepatitis B and infectious mononucleosis. From this perspective, an examination of the AIDS debate is constructed. Molecular biologist Peter Duesberg's argument that HIV is not the cause of AIDS is analyzed in light of his contention that a version of Koch's postulates has not been satisfied. Additional research findings through 1990 relating to the etiology of AIDS are also noted.     

The relationship between virologic and immunologic responses in AIDS clinical research using mixed-effects varying-coefficient models with measurement error

In this article we study the relationship between virologic and immunologic responses in AIDS clinical trials. Since plasma HIV RNA copies (viral load) and CD4+ cell counts are crucial virologic and immunologic markers for HIV infection, it is important to study their relationship during HIV/AIDS treatment. We propose a mixed-effects varying-coefficient model based on an exploratory analysis of data from a clinical trial. Since both viral load and CD4+ cell counts are subject to measurement error, we also consider the measurement error problem in covariates in our model. The regression spline method is proposed for inference for parameters in the proposed model. The regression spline method transforms the unknown nonparametric components into parametric functions. It is relatively simple to implement using readily available software, and parameter inference can be developed from standard parametric models. We apply the proposed models and methods to an AIDS clinical study. From this study, we find an interesting relationship between viral load and CD4+ cell counts during antiviral treatments. Biological interpretations and clinical implications are discussed.     

Peptide T bolus normalizes the growth hormone secretion pattern in two children with AIDS

In humans, HIV infection reduces growth hormone (GH) secretion contributing to AIDS wasting. In rats, the HIV envelope protein gp120 alone blocks GH secretion both in vitro and in vivo through GH-releasing hormone receptors. Peptide T, a modified octapeptide derived from gp120, normalizes GH secretion. We now report that an intravenous bolus of peptide T normalizes nocturnal GH secretion in two out of three children with AIDS. These results, coupled with the lack of toxicity of this experimental AIDS therapeutic, justify clinical trials for AIDS wasting and pediatric AIDS. A clinical and basic science update on peptide T appears in Current HIV Research.     

A comparison study of models and fitting procedures for biphasic viral dynamics in HIV-1 infected patients treated with antiviral therapies

The study of HIV dynamics is one of the most important developments in recent AIDS research. It has led to a new understanding of the pathogenesis of HIV infection. But, although important findings in HIV dynamics have been published in prestigious scientific journals in the last 5 years, the model-fitting procedures used in these publications have not been studied in any detail. In this paper, we evaluate the performance of four model-fitting procedures proposed and used in biphasic HIV dynamic data analysis via extensive Monte Carlo simulations. We propose some guidelines for practitioners to select an appropriate method for their own data analysis. Real data examples from an AIDS clinical trial are provided as illustrations.     

Some recent results on HIV pathogenesis with implications for therapy and vaccines.

In the third decade of AIDS research, we are still facing most of the challenges that emerged when the disease was characterized. While therapeutic approaches to control HIV infection are available in developed countries, novel principles to combat and prevent HIV infection are needed, due to the high cost and the negative effects of currently available drugs. In addition, it is now clear that this disease cannot be eliminated without a vaccine, which appears to be the only possible weapon to combat HIV in developing countries. We have focused on two approaches to fight HIV; one based on select members of a family of proteins, i.e. beta-chemokines, that we have show to interfere with HIV entry and replication, and another centered on a viral protein, HIV-1 Tat, that is crucially involved in HIV regulation and in some of the pathogenic manifestations of HIV infection. Studies from others and ourselves have shown that these two approaches are now ready to the leave experimental bench and move into clinical testing.     

Virginity Testing: Managing Sexuality in a Maturing HIV/AIDS Epidemic

KwaZulu-Natal province in South Africa is currently the site of the world's fastest growing HIV/AIDS epidemic, where it is estimated that between 30 and 40 percent of the adult population is seropositive for HIV. With support from local politicians and members of various government ministries, several self-styled guardians of tradition have emerged to form organizations that advocate and conduct regular virginity testing of girls. Reference to the current HIV/AIDS epidemic is central to calls for greater support of this practice. Drawing on original research among Zulu-speaking people in the periurban communities of Durban, this article examines the sociocultural construction of HIV/AIDS and locates the growing popularity of virginity testing within a gendered meaning-making process consistent with commonly held beliefs that the epidemic is the result of women being sexually "out of control." With the social impact of AIDS starting to take its toll in the forms of increasing AIDS-related deaths and a growing population of orphans, I argue that virginity testing is an attempt to manage the epidemic by exerting greater control over women and their sexuality. In addition, virginity testing of girls helps to draw attention away from the role of men in the maturing epidemic, consideration of which has been conspicuously absent in the popular discourse on AIDS at all levels of South African society.     

HIV/AIDS knowledge, women's education, epidemic severity and protective sexual behaviour in low- and middle-income countries

A fundamental public health strategy to reduce the risk of HIV/AIDS is to increase levels of awareness and knowledge about the disease. Although knowledge about HIV/AIDS and protective sexual behaviour are linked theoretically, relatively little is known about their empirical relationship. Using Demographic and Health Survey data from 23 low- and middle-income countries, this study used multilevel logistic regression models: to examine cross-national variability in the relationship between HIV/AIDS knowledge and protective behaviour (condom use and restricted sex); to investigate the moderating influences of women's educational attainment on this relationship; and to test the extent to which severity of the HIV/AIDS epidemic accounts for cross-national variability in the association between HIV/AIDS knowledge and protective behaviour. There was an association between increased knowledge of HIV/AIDS and condom use that varied in strength and form cross-nationally. This cross-national variation was accounted for partially by the socioeconomic characteristics of women resident in the study countries and between-country differences in the severity of the HIV epidemic. While education modified the association between HIV/AIDS knowledge and protective behaviour--stronger associations at lower levels of education--epidemic severity exerted a stronger influence on behaviour than any other characteristic. Finally, this study indicates that protective sexual practices are disturbingly low. In eight of 23 countries, overall levels of condom use to prevent STDs and HIV/AIDS were less than 5.0%. Waiting for the spread of HIV/AIDS infection to change sexual practices in low- and middle-income countries will result in dramatic unnecessary suffering.     

Keeping the faith: African American faith leaders' perspectives and recommendations for reducing racial disparities in HIV/AIDS infection

In Philadelphia, 66% of new HIV infections are among African Americans and 2% of African Americans are living with HIV. The city of Philadelphia has among the largest numbers of faith institutions of any city in the country. Although faith-based institutions play an important role in the African American community, their response to the AIDS epidemic has historically been lacking. We convened 38 of Philadelphia's most influential African American faith leaders for in-depth interviews and focus groups examining the role of faith-based institutions in HIV prevention. Participants were asked to comment on barriers to engaging faith-based leaders in HIV prevention and were asked to provide normative recommendations for how African American faith institutions can enhance HIV/AIDS prevention and reduce racial disparities in HIV infection. Many faith leaders cited lack of knowledge about Philadelphia's racial disparities in HIV infection as a common reason for not previously engaging in HIV programs; others noted their congregations' existing HIV prevention and outreach programs and shared lessons learned. Barriers to engaging the faith community in HIV prevention included: concerns about tacitly endorsing extramarital sex by promoting condom use, lack of educational information appropriate for a faith-based audience, and fear of losing congregants and revenue as a result of discussing human sexuality and HIV/AIDS from the pulpit. However, many leaders expressed a moral imperative to respond to the AIDS epidemic, and believed clergy should play a greater role in HIV prevention. Many participants noted that controversy surrounding homosexuality has historically divided the faith community and prohibited an appropriate response to the epidemic; many expressed interest in balancing traditional theology with practical public health approaches to HIV prevention. Leaders suggested the faith community should: promote HIV testing, including during or after worship services and in clinical settings; integrate HIV/AIDS topics into health messaging and sermons; couch HIV/AIDS in social justice, human rights and public health language rather than in sexual risk behavior terms; embrace diverse approaches to HIV prevention in their houses of worship; conduct community outreach and host educational sessions for youth; and collaborate on a citywide, interfaith HIV testing and prevention campaign to combat stigma and raise awareness about the African American epidemic. Many African American faith-based leaders are poised to address racial disparities in HIV infection. HIV prevention campaigns should integrate leaders' recommendations for tailoring HIV prevention for a faith-based audience.     

HIV/AIDS and Croatian migrant workers

Due to their geographical mobility and long periods of separation from intimate partners, migrant workers are at increased risk for a variety of sexually transmitted infections (STIs) including HIV/AIDS. This study sought to investigate patterns in HIV/AIDS related knowledge, attitudes and sexual behaviour in migrant workers in Croatia. In 2003, 566 male migrant workers were recruited during regular required medical examinations and surveyed at seven locations throughout the country. Each participant was asked to complete a self-administered KABP (sexual knowledge, attitudes, beliefs and practices) questionnaire. The average age of respondents was 38.2 years and the majority worked as seafarers (77.3%) and construction workers (20.5%). Only 18.5% of respondents were able to correctly answer all 13 questions assessing knowledge of HIV/AIDS. Seafarers reported higher levels of knowledge than did construction workers. The average respondent reported having had two sexual partners in the last 12 months, with slightly over half of the respondents (55.3%) reporting condom use at their last intercourse with a casual partner. One fifth of the respondents (20.3%) who reported having had intercourse with a sex worker during the last year reported not using condoms at last intercourse. The number of sexual partners was correlated with age, marital status, faith in God, and personal HIV risk assessment. Attitudes toward condom use, co-workers' HIV/AIDS concerns and the duration of migrant status (within the last two years) were shown to be significant correlates of condom use at last intercourse with a casual partner. The effect of HIV/AIDS related knowledge on analyzed behaviors did not reach statistical significance. Inadequate patterns of migrant workers' condom use, gaps in knowledge about HIV transmission and modes of protection, as well as widespread ignorance regarding available anonymous HIV testing found by this study suggest a critical need for expert intervention to avert the potential for an increase in new HIV/AIDS cases. A coordinated, systematic campaign for HIV/AIDS prevention among Croatian migrant workers should focus on increasing peer communication about HIV/AIDS, especially among younger migrant workers, and on reducing the frequency of sexual risk taking.     

Evaluating the Impact of Test-and-Treat on the HIV Epidemic among MSM in China Using a Mathematical Model

Background

Various studies have modeled the impact of test-and-treat policies on the HIV epidemics worldwide. However, few modeling studies have taken into account China’s context. To understand the potential effect of test-and-treat on the HIV epidemic among men who have sex with men (MSM) in China, we developed a mathematical model to evaluate the impact of the strategy.

Method

Based on the natural history of the CD4 count of people living with HIV and AIDS (PLWHA), we constructed a dynamic compartmental model of HIV transmission among Chinese MSM to project the number of HIV new infections and prevalence over 10 years. We predicted the annual number of HIV new infections and the total number of MSM living with HIV and AIDS (based on Beijing data) between 2010 and 2022 under the following conditions: (1) current practice (testing rate of 50% and ART coverage of 39%); (2) both testing rate and ART coverage increasing to 70% in 2013; (3) both testing rate and ART coverage increasing to 90% in 2013; and (4) both testing rate and ART coverage increasing gradually every year until 90% since 2013.

Results

Based on our model, if the HIV test-and-treat policy was implemented among Chinese MSM, the total number of HIV new infections over 10 years (2013-2022) would be reduced by 50.6-70.9% compared with the current policy. When ART coverage for PLWHA increased to 58% since 2013, the ‘turning point’ would occur on the curve of HIV new infections by 2015. A 25% reduction in annual number of HIV new infections by 2015 might be achieved if the testing rate increased from 50% to 70% and treatment coverage for PLWHA increased to 55% since 2013.

Conclusion

Implementation of the test-and-treat strategy may significantly reduce HIV new infections among MSM in China. Great efforts need to be made to scale up HIV testing rate and ART coverage among Chinese MSM.     

Studies on virulence of HIV and development of non-virulent live AIDS vaccine using monkeys

A great effort for developing AIDS vaccine has been carried out in the world, designed by various new ideas based on basic research information obtained in recent virology and immunology. Withall it, to obtain effective AIDS vaccine is considered skeptical. One of the reasons of its difficulty is a lack of experimental animals susceptible to HIV-1. In our laboratory, we have succeeded in developing chimeric SIV having 3' half of HIV-1 genome including env (SHIV), which is infectious to macaque monkeys. One of SHIVs has been proved nonpathogenic in monkeys from various aspects and it afforded protective immunity to monkeys against pathogenic SHIV challenge infection. Now, we are trying to develop anti-HIV live attenuated vaccines using the nonpathogenic SHIV as a starting material. In the history of virus vaccine, live attenuated vaccines have been proved most effective in measles and polio-myelitis. However, it is not clear whether nonpathogenic HIV exists or not. Futhermore, even if nonpathogenic HIV could be obtained, there is possibility that it will easily mutate to pathogenic one. Therefore, to develop live attenuated AIDS vaccine is considered dangerous. In this article, We will introduce our research on SHIV pathogenicity using monkeys and hypothesize possibility to obtain nonpathogenic HIV which is speculated from the origin and evolution of HIV/SIV. To clarify virulence and nonvirulence of HIV and to obtain nonpathogenic virus are not only applied research but also basic science to dissolve the fundemental question why HIV can induce the disease.     

Psychological Fears among Low-Paid Female Sex Workers in Southwest China and Their Implications for HIV Prevention

Commercial sex plays a critical role in rapidly increasing heterosexual transmission of HIV in China. Low-paid female sex workers (FSWs) are especially vulnerable to HIV/AIDS. Because of the illegality and stigma associated with sex work, FSWs may constantly live with fears in their daily life. Based on cross-sectional study of 794 low-paid FSWs in China we described their psychological fears related to commercial sex and examined the associations between fears and HIV-related behaviors. Fear of HIV infection was significantly associated with consistent use of condoms with clients. However, fear of breaching sex worker identity significantly prevented the FSWs from consistently using condoms with clients and taking HIV tests. Fear of being arrested by the police was positively associated with consistent use of condoms but negatively associated with accessing HIV prevention services. Our findings underlined the importance of examining the triadic interaction of behavioral, psychological and environmental factors in HIV prevention interventions among low-paid FSWs.     

An epidemic like any other? Rights and responsibilities in HIV prevention.

Throughout the 1980s and into the 1990s, HIV prevention has been closely associated with the protection of individual human rights. Traditional public health measures such as compulsory testing and isolation have largely been rejected as ineffective in public health terms and inappropriate in the context of human rights protection. HIV prevention has been based instead chiefly on elective measures --information, education, counselling, and voluntary testing. In the past five years there have been important clinical, epidemiological, and social developments in the AIDS epidemic. These changes, combined with a growing recognition of possible weaknesses inherent in a strictly voluntarist approach to HIV prevention, may herald a new approach to AIDS control which places more weight on social responsibility in the context of HIV prevention.