Infect. Dis. Rep., Volume 5, Issue s1 (June 2013) – 8 articles

Human immunodeficiency virus type 1 is associated with the development of neurocognitive disorders in many infected individuals, including a broad spectrum of motor impairments and cognitive deficits. Despite extensive research, the pathogenesis of HIV-associated neurocognitive disorders (HAND) is still not clear. This review provides a comprehensive view of HAND, including HIV neuroinvasion, HAND diagnosis and different level of disturbances, influence of highly-active antiretroviral therapy to HIV-associated dementia (HAD), possible pathogenesis of HAD, etc. Together, this review will give a thorough and clear understanding of HAND, especially HAD, which will be vital for future research, diagnosis and treatment. Full article

Around 33 million people worldwide are living with Human Immunodeficiency Virus (HIV) infection, and approximately 20-30% of HIV-infected individuals are also infected with Hepatitis C virus (HCV). The main form of HCV transmission is via the blood borne route; high rates of co-infection are found in intravenous drug users with HCV prevalence rates as high as 90%. Introduction of effective anti-retroviral therapy (ART) has led to a significant decline in HIV-related morbidity, but at the same time the incidence of HCV related liver disease is increasing in the co-infected population. Meta analysis has revealed that individuals who are co-infected with HIV/HCV harbor three times greater risk of progression to liver disease than those infected with HCV alone. Increased risk of progression to Acquired Immunodeficiency Syndrome (AIDS) and AIDS-related deaths is shown among the co-infected patients by some studies, suggesting that HCV infection may accelerate the clinical course of HIV infection. HCV may also affect the incidence of liver toxicity associated with ART, affecting the management of HIV infection. There is a lack of optimal therapeutic approaches to treat HCV infection in HIV co-infected patients. This review discusses recent literature pertaining HIV/HCV co-infection, in addition to providing a snapshot of impact of co-infection on human genome at the level of gene expression and its regulation by microRNAs (miRNAs). Full article

Over the past three decades of intense research on the contribution of viral and host factors determining the variability in HIV-1 infection outcome, HIV pathogenesis is still a fascinating topic that requires further study. An understanding of the exact mechanism of how these factors influencing HIV pathogenesis is critical to the development of effective strate- gies to prevent infection. Significant progress has been made in identifying the role of CCR5 (R5) and CXCR4 (X4) HIV strains in disease progression, particularly with the persistence of R5 HIV-1 strains at the AIDS stage. This indicates that R5 strains are as fit as X4 in causing CD4+ T cell depletion and in contribution to disease outcome, and so questions the prerequisite of the shift from R5 to X4 for disease progression. In contrast, the ability of certain HIV strains to readily use CXCR4 for infection or entry into macrophages, as the case with viruses are homozygous for tropism by CCR5delta32. This raises another major paradox in HIV pathogenesis about the source of X4 variants and how do they emerge from a relatively homogeneous R5 viral population after transmission. The interactions between viral phenotypes, tropism and co-receptor usage and how they influence HIV pathogenesis are the main themes addressed in this review. A better understanding of the viral and host genetic factors involved in the fitness of X4 and R5 strains of HIV-1 may facilitate development of specific inhibitors against these viral populations to at least reduce the risk of disease progression. Full article

Access to combination antiretroviral treatment (ART) has improved greatly over recent years. At the end of 2011, more than eight million HIV-infected people were receiving ART in low-income and middle-income countries. ART generally works well in keeping the virus suppressed and the patient healthy. However, treatment only works as long as the virus is not resistant against the drugs used. In the last decades, HIV treatments have become better and better at slowing down the evolution of drug resistance, so that some patients are treated for many years without having any resistance problems. However, for some patients, especially in low-income countries, drug resistance is still a serious threat to their health. This essay will review what is known about transmitted and acquired drug resistance, multi-class drug resistance, resistance to newer drugs, resistance due to treatment for the prevention of mother-to-child transmission, the role of minority variants (low-frequency drug-resistance mutations), and resistance due to pre-exposure prophylaxis. Full article

One of the major characteristics of HIV-1 is its high genetic variability and extensive heterogeneity. This characteristic is due to its molecular traits, which in turn allows it to vary, recombine, and diversify at a high frequency. As such, it generates complex molecular forms, termed recombinants, which evade the human immune system and so survive. There is no sequence constraint to the recombination pattern as it appears to occur at inter-group (between groups M and O), as well as inter- and intra-subtype within group M. Rapid emergence and active global transmission of HIV-1 recombinants, known as circulating recombinant forms (CRFs) and unique recombinant forms (URFs), requires urgent attention. To date, 55 CRFs have been reported around the world. The first CRF01_AE originated from Central Africa but spread widely in Asia. The most recent CRF; CRF55_01B is a recombinant form of CRF01_AE and subtype B, although its origin is yet to be publicly disclosed. HIV-1 recombination is an ongoing event and plays an indispensable role in HIV epidemics in different regions. Africa, Asia and South America are identified as recombination hot-spots. They are affected by continual emergence and co-circulation of newly emerging CRFs and URFs, which are now responsible for almost 20% of HIV-1 infections worldwide. Better understanding of recombinants is necessary to determine their biological and molecular attributes. Full article

The intra-host evolutionary and population dynamics of the human immunodeficiency virus type 1 (HIV-1), the cause of the acquired immunodeficiency syndrome, have been the focus of one of the most extensive study efforts in the field of molecular evolution over the past three decades. As HIV-1 is among the fastest mutating organisms known, viral sequence data sampled over time from infected patients can provide, through phylogenetic analysis, significant insights about the tempo and mode of evolutionary processes shaped by complex interaction with the host milieu. Five main aspects are discussed: the patterns of HIV-1 intra-host diversity and divergence over time in relation to different phases of disease progression; the impact of selection on the temporal structure of HIV-1 intra-host genealogies inferred from longitudinally sampled viral sequences; HIV-1 intra-host sub-population structure; the potential relationship between viral evolutionary rate and disease progression and the central evolutionary role played by recombination occurring in super-infected cells. Full article

As the world enters the fourth decade of the HIV/AIDS epidemic a number of new drugs have been developed that address current challenges with antiretroviral therapy (ART), such as pill burden, toxicity and drug-resistance. These new agents have not only been developed from established drug-classes, namely nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), but also include innovative ways of suppressing viral replication. Intergrase inhibitors and chemokine receptor blockers have been developed which, combined with NRTIs, NNRTIs and PIs, comprise highly active antiretroviral therapy regimens able to tackle all aspects of the HIV life cycle with minimal toxicity. Furthermore, the ability of pharmaceutical companies to formulate these powerful drugs into fixed-dose combinations provides exciting new strategies for reducing pill burden, thus ensuring adherence and limiting the emergence of drug-resistance. The enthusiasm with which these new drugs have been received has, however, been tempered by the reality of limited access in the developing world, further highlighting the disparity between rich and poor countries in the fight against HIV/ AIDS. Access to these treatments in low- and middle-income countries will require the necessary political will, regulatory approval, affordability of drugs, as well as efficient procurement and supply management strategies. The priority of developing countries remains increased scale up of ART, but there is also a need to acquire new drugs in order to tackle toxicity and drug-resistance, both of which threaten the sustainability of such programmes. Thankfully, the vast majority of patients receiving ART in the developing world are still on first-line regimens, thus allowing time for newer agents to be made available as part of third-line treatment option. However, there is no room for complacency - the developing world needs access to new HIV treatments, an AIDS-free generation depends upon it. Full article