What impact might the economic crisis have on HIV epidemics in Southeast Asia?

Objective: To evaluate the potential impact of the current global economic crisis (GEC) on the spread of HIV. Design: To evaluate the impact of the economic downturn we studied two distinct HIV epidemics in Southeast Asia: the generalized epidemic in Cambodia where incidence is declining and the epidemic in Papua New Guinea (PNG) which is in an expansion phase. Methods: Major HIV-related risk factors that may change due to the GEC were identified and a dynamic mathematical transmission model was developed and used to forecast HIV prevalence, diagnoses, and incidence in Cambodia and PNG over the next 3 years. Results: In Cambodia, the total numbers of HIV diagnoses are not expected to be largely affected. However, an estimated increase of up to 10% in incident cases of HIV, due to potential changes in behavior, may not be observed by the surveillance system. In PNG, HIV incidence and diagnoses could be more affected by the GEC, resulting in respective increases of up to 17% and 11% over the next 3 years. Decreases in VCT and education programs are the factors that may be of greatest concern in both settings. A reduction in the rollout of antiretroviral therapy could increase the number of AIDS-related deaths (by up to 7.5% after 3 years). Conclusions: The GEC is likely to have a modest impact on HIV epidemics. However, there are plausible conditions under which the economic downturns can noticeably influence epidemic trends. This study highlights the high importance of maintaining funding for HIV programs.

The spectrum of HIV-1 related cancers in South Africa

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5–38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7–9.5), vulval cancer (OR=4.8, 95%CI=1.9–12.2) and cervical cancer (OR=1.6, 95%CI=1.1–2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.

Predictors of recent HIV testing among male street laborers in urban Vietnam

This study assessed the prevalence of and factors associated with HIV testing among male street laborers. In a cross-sectional survey, social mapping was done to recruit and interview 450 men aged 18–59 years in Hanoi. Although many of these men engaged in multiple risk behaviors for HIV, only 19.8 percent had been tested for HIV. A modified theoretical model provided better fit than the conventional Information–Motivation–Behavioral Skills model, as it explained much more variance in HIV testing. This model included three Information–Motivation–Behavioral components and four additional factors, namely, the origin of residence, sexual orientation, the number of sexual partners, and the status of condom use.

Creating new folk opera forms of applied theatre for HIV and AIDS education in Papua New Guinea

This research investigated the potential of folk opera as a tool for HIV and AIDS education in Papua New Guinea. It began with an investigation on the indigenous performativities and theatricalities of Papua New Guineans, conducting an audit of eight selected performance traditions in Papua New Guinea. These traditions were analysed, and five cultural forms and twenty performance elements were drawn out for further exploration. These elements were fused and combined with theatre techniques from western theatre traditions, through a script development process involving Australians, Papua New Guineans and international collaborators. The resulting folk opera, entitled Kumul, demonstrates what Murphy (2010) has termed story force, picture force, and feeling force, in the service of a story designed to educate Papua New Guinean audiences about HIV and the need to adopt safer sexual practices. Kumul is the story of a young man faced with decisions on whether or not to engage in risky sexual behaviours. Kumul's narrative is carefully framed within selected Papua New Guinean beliefs drawn from the audit to deliver HIV and AIDS messages using symbolic and metaphoric communication techniques without offending people. The folk opera Kumul was trialled in two communities in Papua New Guinea: a village community and an urban settlement area. Kumul is recognisable to Papua New Guinean audiences because it reflects their lifestyle and a worldview, which connects them to their beliefs and spirituality, and the larger cosmological order. Feedback from audience members indicated that the performance facilitated HIV and AIDS communication, increased people's awareness of HIV and AIDS, and encouraged behaviour change. Tellingly, in one performance venue, forty people queued for Voluntary Testing and Counseling immediately after the performance. Twenty of these people were tested on that night and the other twenty were tested the following day. Many of the volunteers were young men – a demographic historically difficult to engage in HIV testing. This encouraging result indicates that the Kumul folk opera form of applied theatre could be useful for facilitating communication and education regarding sexual health and safer sexual behaviours in Papua New Guinea. Feedback from participants, audience members and other research stakeholders suggests that the form might also be adapted to address other social and development issues, particularly in the areas of health and social justice.

Children living in HIV families : a review

This review article summarizes the current knowledge about children born or living in families affected by HIV, a topic of recent interest in the HIV field. It also presents a case study of a child's narrative about the implications of living with a HIV parent. The case study is part of a larger study involving both parents and children living with HIV in Bangladesh. The paper discusses the implications of HIV for children, their families, and social services to gain a better understanding of some of the social issues, such as stigma, associated with this illness. The paper recommends that the development of effective social and service interventions using appropriate language, information, and access to social support services are urgently needed to reduce the concerns and increases the life opportunities of children living in HIV families.

Model refinement through high-performance computing: an agent-based HIV example

Background Recent advances in Immunology highlighted the importance of local properties on the overall progression of HIV infection. In particular, the gastrointestinal tract is seen as a key area during early infection, and the massive cell depletion associated with it may influence subsequent disease progression. This motivated the development of a large-scale agent-based model. Results Lymph nodes are explicitly implemented, and considerations on parallel computing permit large simulations and the inclusion of local features. The results obtained show that GI tract inclusion in the model leads to an accelerated disease progression, during both the early stages and the long-term evolution, compared to a theoretical, uniform model. Conclusions These results confirm the potential of treatment policies currently under investigation, which focus on this region. They also highlight the potential of this modelling framework, incorporating both agent-based and network-based components, in the context of complex systems where scaling-up alone does not result in models providing additional insights.

Multi-layered model of individual HIV infection progression and mechanisms of phenotypical expression

Cite as: Perrin, Dimitri (2008) Multi-layered model of individual HIV infection progression and mechanisms of phenotypical expression. PhD thesis, Dublin City University.

Michael Kirby's challenge: Intellectual property, HIV/AIDS, and human rights

In July 2014, Melbourne hosted the 20th International AIDS Conference. The event opened, paying tribute to the late Dutch HIV/AIDS researcher Professor Joep Lange, with his image projected onto a screen, with the accompanying quotation: ‘If we can bring a bottle of Coke to every corner of Africa, we should be able to also deliver antiretroviral drugs.’

A qualitative exploration of parental experiences of stigma while living with HIV in Bangladesh

With much of the focus on the “risk” groups, families have often been less studied in HIV research. Further, because of a focus on the aetiology and epidemiology of HIV, the social impacts associated with HIV on families and neighbours are sometimes overlooked. This study examined parental experiences of stigma and discrimination while living with HIV within a family context in Bangladesh. A qualitative research design using a grounded theory approach was used for this research. Data was collected through in-depth interviews with 19 HIV-positive parents, recruited with the support of two self-help groups of HIV-positive people, in two settings namely Khulna and Dhaka in Bangladesh. The findings indicate that HIV-positive parents held the view that they continue to experience significant stigma and their narratives clearly show how this affected them and their children. A range of informal practices were enacted in everyday contexts by extended family and community members to identify, demarcate and limit the social interaction of HIV-positive parents. Parents highlighted a number of factors including negative thoughts and behaviours, rejection, isolation and derogatory remarks as manifestations of stigma and discrimination, impacting upon them and their children because of their association with HIV.

Monoclonal antibody screening of a phage-displayed random peptide library reveals mimotopes of chemokine receptor CCR5: Implications for the tertiary structure of the receptor and for an n-terminal binding site for HIV-1 gp120

The chemokine receptor CCR5 contains seven transmembrane-spanning domains. It binds chemokines and acts as co-receptor for macrophage (m)-tropic (or R5) strains of HIV-1. Monoclonal antibodies (mAb) to CCR5, 3A9 and 5C7, were used for biopanning a nonapeptide cysteine (C)-constrained phage-displayed random peptide library to ascertain contact residues and define tertiary structures of possible epitopes on CCR5. Reactivity of antibodies with phagotopes was established by enzyme-linked immunosorbent assay (ELISA). mAb 3A9 identified a phagotope C-HASIYDFGS-C (3A9/1), and 5C7 most frequently identified C-PHWLRDLRV-C (5C7/1). Corresponding peptides were synthesized. Phagotopes and synthetic peptides reacted in ELISA with corresponding antibodies and synthetic peptides inhibited antibody binding to the phagotopes. Reactivity by immunofluorescence of 3A9 with CCR5 was strongly inhibited by the corresponding peptide. Both mAb 3A9 and 5C7 reacted similarly with phagotopes and the corresponding peptide selected by the alternative mAb. The sequences of peptide inserts of phagotopes could be aligned as mimotopes of the sequence of CCR5. For phage 3A9/1, the motif SIYD aligned to residues at the N terminus and FG to residues on the first extracellular loop; for 5C7/1, residues at the N terminus, first extracellular loop, and possibly the third extracellular loop could be aligned and so would contribute to the mimotope. The synthetic peptides corresponding to the isolated phagotopes showed a CD4-dependent reactivity with gp120 of a primary, m-tropic HIV-1 isolate. Thus reactivity of antibodies raised to CCR5 against phage-displayed peptides defined mimotopes that reflect binding sites for these antibodies and reveal a part of the gp120 binding sites on CCR5.

Timing the Emergence of Resistance to Anti-HIV Drugs with Large Genetic Barriers

New antiretroviral drugs that offer large genetic barriers to resistance, such as the recently approved inhibitors of HIV-1 protease, tipranavir and darunavir, present promising weapons to avert the failure of current therapies for HIV infection. Optimal treatment strategies with the new drugs, however, are yet to be established. A key limitation is the poor understanding of the process by which HIV surmounts large genetic barriers to resistance. Extant models of HIV dynamics are predicated on the predominance of deterministic forces underlying the emergence of resistant genomes. In contrast, stochastic forces may dominate, especially when the genetic barrier is large, and delay the emergence of resistant genomes. We develop a mathematical model of HIV dynamics under the influence of an antiretroviral drug to predict the waiting time for the emergence of genomes that carry the requisite mutations to overcome the genetic barrier of the drug. We apply our model to describe the development of resistance to tipranavir in in vitro serial passage experiments. Model predictions of the times of emergence of different mutant genomes with increasing resistance to tipranavir are in quantitative agreement with experiments, indicating that our model captures the dynamics of the development of resistance to antiretroviral drugs accurately. Further, model predictions provide insights into the influence of underlying evolutionary processes such as recombination on the development of resistance, and suggest guidelines for drug design: drugs that offer large genetic barriers to resistance with resistance sites tightly localized on the viral genome and exhibiting positive epistatic interactions maximally inhibit the emergence of resistant genomes.

Structural Basis of Drug Resistance by Genetic Variants of HIV Type 1 Clade C Protease from India

Using computer modeling of three-dimensional structures and structural information available on the crystal structures of HIV-1 protease, we investigated the structural effects of mutations, in treatment-naive and treatment-exposed individuals from India and postulated mechanisms of resistance in clade C variants. A large number of models (14) have been generated by computational mutation of the available crystal structures of drug bound proteases. Localized energy minimization was carried out in and around the sites of mutation in order to optimize the geometry of interactions present. Most of the mutations result in structural differences at the flap that favors the semiopen state of the enzyme. Some of the mutations were also found to confer resistance by affecting the geometry of the active site. The E35D mutation affects the flap structure in clade B strains and E35N and E35K mutation, seen in our modeled strains, have a more profound effect. Common polymorphisms at positions 36 and 63 in clade C also affected flap structure. Apart from a few other residues Gln-58, Asn-83, Asn-88, and Gln-92 and their interactions are important for the transition from the closed to the open state. Development of protease inhibitors by structure-based design requires investigation of mechanisms operative for clade C to improve the efficacy of therapy.

Immunointervention for patients with HIV and tuberculosis

Therapeutic options aimed at confronting the HIV pandemic face many obstacles. Current opinion on HIV-induced pathogenic immune activation and strategies aimed at eliminating HIV, including a potential role for non-neutralising antibodies as part of a therapeutic vaccine option, was elegantly reviewed by Martin Cadogan and Angus Dalgleish. 1 It is important to note that, for eliciting such antibody responses in patients, functionally fit antigen presenting cells and effector T and B cells are cruc.

The influence of HIV infection to the periodontium; a clinical, microbiological, and enzymological study

The main targets of human immunodeficiency virus (HIV) are CD4 receptors of CD4+ lymphocytes and many other cells such as monocytes/macrophages, megakaryocytes, peripheral blood dendritic cells, follicular dendritic cells (DC), epidermal Langerhans cells, and astrocytes. Infection and killing of CD4+ lymphocytes or false reaction of the body to HIV infection and the spontaneous apoptosis of CD4+ lymphocytes decrease CD4+ lymphocyte counts leading to immunosuppression, further disease progression, and appearance of opportunistic infections and malignancies. Oral manifestations are considered to be among the first signs of HIV infection. Enhanced degradation of extracellular matrix and basement membrane components in oral diseases including periodontitis is caused by Zn-dependent enzymes called matrix metalloproteinases (MMPs). The levels and degrees of activation of MMP-1, -2, -3, -7, -8, -9, -25, -26, tissue inhibitors of MMPs (TIMP)-1 and -2, and myeloperoxidase (MPO) and collagenolytic/gelatinolytic activities, and also Ig A, -G, and -M, total protein, and albumin levels in a two-year follow-up were studied from salivary samples. The expression of MMP-7, -8, -9, -25, and -26 immunoreactivities in gingival tissue specimens were studied. Healthy HIV-negative subjects served as controls. All studied clinical periodontal parameters and microbiological evaluation of the periodontopathogens showed that periodontal health of the HIV-positive patients was moderately decreased in comparison to the healthy controls. The levels of Candida in the periodontal pockets and salivary MPO increased with the severity of HIV infection. Immunoreactivities and levels of MMPs and TIMPs, and MMP activities (collagenase, gelatinase) were enhanced in the HIV-positive patient salivary samples relative to the healthy controls regardless of the phase of HIV infection. However, these parameters did not reflect periodontal status in a similar way as in the generally healthy periodontitis patients. Salivary total protein, albumin, IgA, -G, and -M levels were significantly higher in all phases of HIV infection compared to the controls, and salivary total protein, IgG and IgM levels remained higher after two years follow-up, partly correlating with the disease progression and which may reflect the leakage of serum components into the mouth and thus a decreased mucosal barrier. Salivary analyses of MMPs and TIMPs with immunohistochemical analyses showed that HIV infection could predispose to periodontal destruction when compared with healthy controls or the body s defence reactions associated with HIV infection may have been reflected or mediated by MMPs.

Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 × 10−28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 × 10−14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 × 10−9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.