HIV Treatment Proceeds as Prevention Research Confounds
PLoS Med 2007 Dec 1;4(12):e347 doi:10.1371/journal.pmed.0040347
Virginia Barbour, Paul Chinnock, Larry Peiperl, Emma Veitch, and Gavin Yamey, the PLoS Medicine Editors
In this context of global progress toward HIV treatment, the official theme of World AIDS Day 2007 appropriately calls on "Leadership" to "Keep the Promise" of universal access to HIV care and services.
Cytomegalovirus Retinitis: The Neglected Disease of the AIDS Pandemic
PLoS Med 2007 Dec 1;4(12):e334 doi:10.1371/journal.pmed.0040334
Heiden D, Ford N, Wilson D, Rodriguez WR, Margolis T, et al.
Simple and effective management of CMV disease in resource-poor settings is a realistic goal, and one that has been overlooked in the scale-up of HIV treatment worldwide. Ongoing CMV-related mortality should no longer go unrecognized or be accepted as part of advanced HIV mortality. Patients should not be left vulnerable to blindness while clinicians are in the process of treating and controlling the underlying infection with HIV.
Should We Include Connection Domain Mutations of HIV-1 Reverse Transcriptase in HIV Resistance Testing
PLoS Med 2007 Dec 1;4(12): e346 doi:10.1371/journal.pmed.0040346
Götte M
The data presented in this study help to shed light on complex resistance patterns and provide a rationale for including the N348I mutation in genotypic testing. Hachiya and colleagues have recently identified the N348I mutation in clinical isolates that showed decreased susceptibility to NVP in the absence of known NNRTI-associated mutations. Thus, the inclusion of N348I, and possibly also other connection mutations, may be considered in the context of routine genotyping. Clinical studies that are designed to assess a potential benefit of including connection mutations in HIV resistance testing are required to further address this issue. It will likewise be important to gather similar information on the role of other connection mutations and possibly RNase H–associated mutations. The various locations of known C-terminal mutations in the RT enzyme suggest the involvement of different underlying mechanisms.
Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions: A summary report from a Global HIV Vaccine Enterprise Working Group
PLoS Med 2007 Dec 1;4(12): e348 doi:10.1371/journal.pmed.0040348
David Montefiori, Quentin Sattentau, Jorge Flores, José Esparza, John Mascola, on behalf of a Working Group convened by the Global HIV Vaccine Enterprise
Participants in the workshop identified four areas that, if given proper attention, could provide key information that would bring the field closer to an effective antibody-based HIV-1 vaccine: (1) structure-assisted immunogen design, (2) role of Fc receptors and complement, (3) assay standardization and validation, and (4) immunoregulation of B cell responses.
N348I in the Connection Domain of HIV-1 Reverse Transcriptase Confers Zidovudine and Nevirapine Resistance
PLoS Med 2007 Dec 1;4(12): e335 doi:10.1371/journal.pmed.0040335
Soo-Huey Yap1,2, Chih-Wei Sheen3, Jonathan Fahey1,4, Mark Zanin1, David Tyssen1, Viviane Dias Lima5, Brian Wynhoven5, Michael Kuiper6, Nicolas Sluis-Cremer3, P. Richard Harrigan5, Gilda Tachedjian1,4,7*
This study provides the first in vivo evidence that treatment with RT inhibitors can select a mutation (i.e., N348I) outside the polymerase domain of the HIV-1 RT that confers dual-class resistance. Its emergence, which can happen early during therapy, may significantly impact on a patient's response to antiretroviral therapies containing zidovudine and nevirapine. This study also provides compelling evidence for investigating the role of other mutations in the connection and RNase H domains in virological failure.
Elevated Risk for HIV Infection among Men Who Have Sex with Men in Low- and Middle-Income Countries 2000–2006: A Systematic Review
PLoS Med 2007 Dec 1;4(12): e339 doi:10.1371/journal.pmed.0040339
Stefan Baral1,2,3, Frangiscos Sifakis1,2, Farley Cleghorn4, Chris Beyrer1,2
MSM have a markedly greater risk of being infected with HIV compared with general population samples from low- and middle-income countries in the Americas, Asia, and Africa. ORs for HIV infection in MSM are elevated across prevalence levels by country and decrease as general population prevalence increases, but remain 9-fold higher in medium–high prevalence settings. MSM from low- and middle-income countries are in urgent need of prevention and care, and appear to be both understudied and underserved.
When Do HIV-Infected Women Disclose Their HIV Status to Their Male Partner and Why? A Study in a PMTCT Programme, Abidjan
PLoS Med 2007 Dec 1; 4(12): e342 doi:10.1371/journal.pmed.0040342
Hermann Brou1,2, Gérard Djohan2, Renaud Becquet3,4, Gérard Allou4, Didier K. Ekouevi5, Ida Viho5, Valériane Leroy3,4, Annabel Desgrées-du-Loû1*, ANRS 1201/1202/1253 Ditrame Plus Study Group
In PMTCT programmes, specific psychosocial counselling and support should be provided to women during the key moments of disclosure of HIV status to their partners (end of pregnancy, weaning, and resumption of sexual activity). This support could contribute to improving women's adherence to the advice given to prevent postnatal and sexual HIV transmission.
Assessment of Recent HIV-1 Infection by a Line Immunoassay for HIV-1/2 Confirmation
PLoS Med 2007 Dec 1; 4(12): e343 doi:10.1371/journal.pmed.0040343
Jörg Schüpbach1, Martin D. Gebhardt2, Zuzana Tomasik1, Christoph Niederhauser3, Sabine Yerly4, Philippe Bürgisser5, Lukas Matter6, Meri Gorgievski7, Rolf Dubs8, Detlev Schultze9, Ingrid Steffen10, Corinne Andreutti11, Gladys Martinetti12, Bruno Güntert13, Roger Staub2, Synove Daneel14, Pietro Vernazza14
Recency information can be extracted from INNO-LIA-based confirmatory testing at no additional costs. This method should improve epidemiologic surveillance in countries that routinely use INNO-LIA for HIV confirmation.
Evolution of Antiretroviral Drug Costs in Brazil in the Context of Free and Universal Access to AIDS Treatment
PLoS Med 2007 Nov 13; 4(11): e305 doi:10.1371/journal.pmed.0040305
Amy S. Nunn1, Elize M. Fonseca2,3, Francisco I. Bastos2, Sofia Gruskin1,4, Joshua A. Salomon1,5
Despite Brazil's more costly generic ARVs, the net result of ARV price changes has been a cost savings of approximately US$1 billion since 2001. HAART costs have nevertheless risen steeply as Brazil has scaled up treatment. These trends may foreshadow future AIDS treatment cost trends in other developing countries as more people start treatment, AIDS patients live longer and move from first-line to second and third-line treatment, AIDS treatment becomes more complex, generic competition emerges, and newer patented drugs become available. The specific application of the Brazilian model to other countries will depend, however, on the strength of their health systems, intellectual property regulations, epidemiological profiles, AIDS treatment guidelines, and differing capacities to produce drugs locally.
Squaring the Circle: AIDS, Poverty, and Human Development
PLoS Med 2007 Oct 23; 4(10): e314 doi:10.1371/journal.pmed.0040314
Peter Piot, Robert Greener, Sarah Russell
AIDS, it has been said, is exceptional in terms of its threat to humanity, and its complexity. The relationship between AIDS and poverty is just one example of that complexity, having more to do with inequality than poverty per se.
Food Insufficiency Is Associated with High-Risk Sexual Behavior among Women in Botswana and Swaziland
PLoS Med 2007 Oct 23; 4(10): e260 doi:10.1371/journal.pmed.0040260
Sheri D. Weiser1,2,3, Karen Leiter1, David R. Bangsberg2,4, Lisa M. Butler5, Fiona Percy-de Korte1, Zakhe Hlanze6, Nthabiseng Phaladze7, Vincent Iacopino1,8, Michele Heisler1,9,10
Food insufficiency is an important risk factor for increased sexual risk-taking among women in Botswana and Swaziland. Targeted food assistance and income generation programs in conjunction with efforts to enhance women’s legal and social rights may play an important role in decreasing HIV transmission risk for women.
Patient Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa: A Systematic Review
PLoS Med 2007 Oct 16; 4(10): e298 doi:10.1371/journal.pmed.0040298
Sydney Rosen1,2, Matthew P. Fox1, Christopher J. Gill1,3
Since the inception of large-scale ART access early in this decade, ART programs in Africa have retained about 60% of their patients at the end of 2 y. Loss to follow-up is the major cause of attrition, followed by death. Better patient tracing procedures, better understanding of loss to follow-up, and earlier initiation of ART to reduce mortality are needed if retention is to be improved. Retention varies widely across programs, and programs that have achieved higher retention rates can serve as models for future improvements.
HCV–HIV Coinfection: Simple Messages from a Complex Disease
PLoS Med 2007 Oct 9; 4(10): e240 doi:10.1371/journal.pmed.0040240
Paul Klenerman1, Arthur Kim2
In this Research in Translation article, we discuss our current understanding of the immunopathogenesis of HCV–HIV coinfection. We firstly discuss what is known of the host immune response in HCV monoinfection, and subsequently the impact of HIV on this response. We focus on two issues—immune deficiency and immune dysregulation, which we propose combine to produce the clinical picture associated with coinfection.
HIV Denial in the Internet Era
Tara C. Smith*, Steven P. Novella
PLoS Med 2007 Aug 21,4(8): e256 doi:10.1371/journal.pmed.0040256
Because these denialist assertions are made in books and on the Internet rather than in the scientific literature, many scientists are either unaware of the existence of organized denial groups, or believe they can safely ignore them as the discredited fringe. And indeed, most of the HIV deniers' arguments were answered long ago by scientists. However, many members of the general public do not have the scientific background to critique the assertions put forth by these groups, and not only accept them but continue to propagate them. A recent editorial in Nature Medicine [32] stresses the need to counteract AIDS misinformation spread by the deniers.
Male Circumcision for Prevention of HIV Transmission: What the New Data Mean for HIV Prevention in the United States
PLoS Med 2007 Jul 24; 4(7): e223 doi:10.1371/journal.pmed.0040223
Patrick S. Sullivan, Peter H. Kilmarx, Thomas A. Peterman, Allan W. Taylor, Allyn K. Nakashima, Mary L. Kamb, Lee Warner, Timothy D. Mastro
It is now clear that male circumcision can be efficacious for men in reducing their risk of HIV acquisition through sex with women. Some experts predict that the impact of male circumcision as a biomedical intervention for HIV prevention in Africa could be large, and preparatory work has been done to establish male circumcision programs in Africa. The implications of African trials on circumcision for HIV prevention programs in the United States are less clear—despite the interest of the popular press in the idea. Here, we consider the differences between the HIV epidemics in Africa and the US, the current status of male circumcision in the US, and the knowledge gaps that will need to be addressed as we consider whether male circumcision should be evaluated or implemented as a biomedical intervention to reduce sexually acquired HIV infections domestically.
HIV Prevention, Care, and Treatment in Two Prisons in Thailand
David Wilson, Nathan Ford*, Verapun Ngammee, Arlene Chua, Moe Kyaw Kyaw
PLoS Med 4(6): e204 doi:10.1371/journal.pmed.0040204
As scale-up of antiretroviral therapy (ART) progresses in less-developed countries, the challenges of providing treatment to marginalised populations become of increasing concern. One such marginalised group is prisoners. While there is an emerging consensus that prevention and treatment is feasible and effective in prisons [1], experience of implementing comprehensive HIV/AIDS programmes that include antiretroviral therapy in resource-limited countries is limited. This article describes our experience of providing HIV prevention and treatment in two prisons in Thailand.
Late HIV Diagnosis: Bad Medicine and Worse Public Health
Valdiserri RO
PLoS Medicine Vol. 4, No. 6, e200 doi:10.1371/journal.pmed.0040200
It is estimated that there are some 252,000–312,000 Americans living with HIV yet unaware that they carry this deadly virus. Once they develop symptoms of HIV disease, most will be diagnosed. But by then, their immune systems will have experienced permanent damage, and thousands will have inadvertently infected their partners. One analysis reckons that annual HIV transmission rates in the United States are some 3.5 times higher among people with undiagnosed HIV infection compared to those who are diagnosed, due to the fact that knowledge of positive HIV serostatus is associated with substantial decreases in high-risk sexual behaviors among those so diagnosed.
Costs and Consequences of the US Centers for Disease Control and Prevention's Recommendations for Opt-Out HIV Testing
Holtgrave DR
PLoS Medicine Vol. 4, No. 6, e194 doi:10.1371/journal.pmed.0040194
While opt-out testing may be able to newly diagnose over 56,000 persons living with HIV in one year, abandoning client-centered counseling has real public health consequences in terms of HIV infections that could have been averted. Further, my analyses indicate that even when HIV seropositivity rates are as low as 0.3%, targeted counseling and testing performs better than opt-out testing on several key outcome variables. These analytic findings should be kept in mind as HIV counseling and testing policies are debated in the US.
Understanding the Slow Depletion of Memory CD4+ T Cells in HIV Infection
Andrew Yates1,2*, Jaroslav Stark3,4, Nigel Klein5, Rustom Antia1, Robin Callard2,5
PLoS Med 4(5): e177 doi:10.1371/journal.pmed.0040177
A runaway cycle in which elevated CD4+ T cell activation and proliferation drive HIV production and vice versa cannot explain the pace of depletion during chronic HIV infection. We summarize some alternative mechanisms by which the CD4+ memory T cell homeostatic set point might slowly diminish. While none are mutually exclusive, the phenomenon of viral rebound, in which interruption of antiretroviral therapy causes a rapid return to pretreatment viral load and T cell counts, supports the model of virus adaptation as a major force driving depletion.
HIV, Stigma, and Rates of Infection: A Human Rights and Public Health Imperative
Susan Timberlake, Jason Sigurdson
PLoS Medicine Vol. 4, No. 1, e52 doi:10.1371/journal.pmed.0040052
In their essay “HIV, Stigma, and Rates of Infection: A Rumour without Evidence”, Daniel Reidpath and Kit Yee Chan rightly underscore the insuffi cient body of research on the relationship between stigma and discrimination and HIV transmission [1]. Increased scientifi c attention and effective programming against stigma and discrimination are both sorely needed. But the Joint United Nations Programme on HIV/AIDS (UNAIDS) does not accept a number of points made in the essay.
HIV, Stigma, and Rates of Infection: Absence of Evidence
Mark Seielstad
PLoS Medicine Vol. 4, No. 1, e54 doi:10.1371/journal.pmed.0040054
Absence of evidence is not evidence of absence. Reidpath and Chan [1] present absolutely no reasons or data that would undermine the hypothesis that stigmatization can increase the risk of HIV spread in populations (nor any in favor of their own contrary hypothesis that stigmatization could halt the spread of HIV). More data to address the question may be needed to establish either hypothesis, but motivations to collect such data should not come from illogical and infl ammatory counterhypotheses. In the guidelines for correspondence to PLoS Medicine, we are advised that “...letters inciting racial hatred, sexism, or homophobia [will not be published]” [2], but the present authors skirt the commission of such acts very closely. After all, HIV prevalences also differ among races, sexes, and sexual orientations, so the stigmatization of groups with high rates of infection by those with lower rates of infection could be viewed as helpful to the goal of HIV containment. This seems unlikely to be helpful, and would impose a much greater societal cost. This essay is shameful in its intellectual dishonesty and lack of evidence to support its own unappealing counterhypothesis.
HIV, Stigma, and Rates of Infection: A Rumour without Evidence: Authors' Reply
Reidpath DD, Chan KY
PLoS Medicine Vol. 4, No. 1, e44 doi:10.1371/journal.pmed.0040044
In their essay in October’s PLoS Medicine, Daniel Reidpath and Kit Yee Chan challenge the widely cited link between HIV-related stigma and the spread of the epidemic [1]. This is an important question, given the heavy emphasis on stigma in policies of the World Health Organization, the Joint United Programme on HIV/AIDS, and other public health institutions, but in making their argument Reidpath and Chan misrepresent the connections that other authors have made between stigma and viral transmission, ignore evidence that does suggest an association, and propose a model of their own for which they offer no evidence.
XDR-TB in South Africa: No Time for Denial or Complacency
PLoS Med 2007 Jan 23 4(1), e50 doi:10.1371/journal.pmed.0040050
Jerome Amir Singh*, Ross Upshur, Nesri Padayatchi
On September 1, 2006, the World Health Organisation (WHO) announced that a deadly new strain of extensively drugresistant tuberculosis (XDR-TB) had been detected in Tugela Ferry (Figure 1), a rural town in the South African province of KwaZulu-Natal (KZN) [1], the epicentre of South Africa’s HIV/AIDS epidemic. Of the 544 patients studied in the area in 2005, 221 had multi-drug-resistant tuberculosis (MDR-TB), that is, Mycobacterium tuberculosis that is resistant to at least rifampicin and isoniazid. Of these 221 cases, 53 were identifi ed as XDR-TB (see Table 1 and [2]), i.e., MDR-TB plus resistance to at least three of the six classes of second-line agents [3]. This reportedly represents almost one-sixth of all known XDR-TB cases reported worldwide [4]. Of the 53, 44 were tested for HIV and all were HIV infected.
A Novel Substrate-Based HIV-1 Protease Inhibitor Drug Resistance Mechanism
PLoS Med 2007 Jan 16 4(1), e36 doi:10.1371/journal.pmed.0040036
Nijhuis M, van Maarseveen NM, Lastere S, Schipper P, Coakley E, et al.
HIV can use an alternative mechanism to become resistant to PI by changing the substrate instead of the protease. Further studies are required to determine to what extent cleavage site mutations may explain virological failure during PI therapy.
When Is Replacement Feeding Safe for Infants of HIV-Infected Women?
PLoS Med 2007 Jan 16 4(1), e30 doi:10.1371/journal.pmed.0040030
Grace C. John-Stewart
Current research in prevention of breast-milk HIV transmission includes evaluation of a variety of approaches, including optimizing exclusive breastfeeding, providing antiretrovirals during shortened breast-feeding to mother or infant, and, ultimately, vaccination. Preserving breast-feeding is attractive because of nutritional, growth, safety, and confi dentiality issues, and in the future these approaches may enable prolonged breast-feeding. However, some of the interventions currently under study may not be as promising as initially envisioned. For example, highly active antiretroviral therapy (HAART) during shortened breast-feeding is not the panacea hoped for—it may be associated with loss of confi dentiality, toxicity, resistance, and infant morbidity and growth compromise when breast-feeding is stopped at six months. It is plausible that strategizing for not breast-feeding from birth would be less problematic than first starting to breast-feed on HAART, and then stopping after six months. Thus, replacement feeding should still be considered in the mix of strategies to prevent breast-milk transmission of HIV, particularly when water safety is assured and provision of breast-milk substitutes is an option. Becquet et al’s data are reassuring that when appropriate support is provided and clean water is available, replacement feeding can be safe in an urban African setting.
Two-Year Morbidity–Mortality and Alternatives to Prolonged Breast-Feeding among Children Born to HIV-Infected Mothers in Coˆ te d’Ivoire
PLoS Med 2007 Jan 16 4(1), e17 doi:10.1371/journal.pmed.0040017
Renaud Becquet1*, Laurence Bequet2, Didier K. Ekouevi2, Ida Viho2, Charlotte Sakarovitch1, Patricia Fassinou3, Gédéon Bedikou2, Marguerite Timite-Konan3, François Dabis1, Vale´riane Leroy1, ANRS 1201/1202 Ditrame Plus Study Group1,2
The 2-y rates of adverse health outcomes were similar among short-term breast-fed and formula-fed children. Mortality rates did not differ significantly between these two groups and, after adjustment for pediatric HIV status, were similar to those observed among long-term breast-fed children. Given appropriate nutritional counseling and care, access to clean water, and a supply of breast-milk substitutes, these alternatives to prolonged breast-feeding can be safe interventions to prevent mother-to-child transmission of HIV in urban African settings.