Eleventh International Congress on Drug Therapy in HIV Infection
2012; International AIDS Society; Volume: 15; Linguagem: Inglês
10.7448/ias.15.6.18447
ISSN1758-2652
Tópico(s)HIV-related health complications and treatments
ResumoJournal of the International AIDS SocietyVolume 15, Issue S4 18447 Supplement - complete fileOpen Access Eleventh International Congress on Drug Therapy in HIV Infection First published: 11 November 2012 https://doi.org/10.7448/IAS.15.6.18447AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Keynote Lecture – KL1 Abstract The efficiency of transmission of HIV depends on the infectiousness of the index case and the susceptibility of those exposed. Infectiousness is dictated by the concentration of HIV-1 in relevant fluids (regardless of route of transmission) and the viral genotype and phenotype. People newly infected with HIV-1 (i.e. acute infection) and those with STI co-infections excrete such a large concentration of virus as to be “hyperinfectious.” The actual transmission of HIV likely occurs in the first few hours after exposure. The probability of transmission may be as low as 1/10,000 episodes of intercourse or 1/10 sexual exposures when anal intercourse is practiced. The transmission of HIV is generally limited to one or a small number of founder variants which themselves may be “hyperinfectious.” Synergistic behavioural and biologic HIV prevention strategies have been developed and implemented. Safer sex includes limiting the number of sexual partners, use of male latex condoms, and structural interventions to reduce exposure. These strategies appear to have contributed to reduced HIV incidence in many countries. Biological interventions have proved catalytic: these include treatment of inflammatory cofactors, voluntary male circumcision and use of antiviral agents either for infected people (who can be rendered remarkably less contagious) or as pre- and post-exposure prophylaxis (PrEP and PEP). Ecologic evidence suggests that broader, earlier antiviral treatment of HIV may be reducing incidence in some (but not all) populations. However, maximal benefit of HIV “treatment for prevention” and application of PrEP will likely require a program of universal “test and treat,” where many more infected patients are identified, linked to care, and treated very early in disease and for life. Community randomized trials designed to support this approach are under way in Africa. The “test and treat” prevention strategy is resource-intensive and serves to emphasize research that searches for a cure for HIV infection so that people living with HIV can eventually reduce or stop treatment. Likewise, success in HIV prevention emphasizes the importance of development of an HIV vaccine, which remains focused on agents that may evoke CTL responses, antibody dependent cytotoxicity, and (perhaps most important) broad neutralizing antibodies. A human clinical trial (RV144) and animal experiments have provided hope, excitement and a roadmap for development of an HIV vaccine. 10.7448/IAS.15.6.18066 © 2012 Cohen M; licensee International AIDS Society Published 11 November 2012 Keynote Lecture – KL2 Abstract Once a retrovirus infects a eukaryotic cell and integrates within chromosomal DNA, it becomes part of its genome and can be activated/transcribed/translated to produce viral proteins and/or new viral particles. Over the years, some of these retroviruses may lose their pathogenicity and become adapted to the new host. Under these conditions, retroviruses can paradoxically ameliorate the functional portfolio of the infected cell, thus potentially increasing its functionality and/or chances of survival in a difficult environment. Individuals whose cells are infected by retroviruses have acquired, in the last millions of years, innovative functions that, once transmitted to the new generation through germinal cells, have become essential for their homeostasis, or even for their survival. This is the case of some endogenous retroviruses, whose products are mandatory for the proper vascularization of human placenta. To our knowledge, there are no natural means able to selectively eliminate retroviral genes from an infected cell or an individual. Therefore, the chances of getting naturally cured by retroviruses, once infection is set and viral genomes are spread into the body, are minimal or absent. HIV is a retrovirus that behaves as all other retroviruses that interacted with humans in the past millennia. Its fate is to remain forever within the infected body. For these reasons, the chances of getting rid of HIV infection and being biologically cured (that is, eliminating all viral genomes from the body) are very limited if we consider current knowledge, biotechnology and available medical tools (yet it cannot be fully excluded in very peculiar cases). The option offered by the so-called “functional cure” is different. In this case, medical manipulation may create conditions whereby viral genomes, decreased in number and function by proper therapies/vaccines, are no longer able to harm the host for an indefinite period of time. Patients do remain infected, but viral replicative cycles are absent, and progression of the disease is interrupted. This latter clinical approach may be suitable, and this is where clinical research is directing its efforts. If achievable, infected persons should cope with the virus and keep it under control for decades, without support of chronic antiviral therapy. In conclusion, the proper knowledge of the biological characteristics of HIV helps in selecting the best strategies aimed at obtaining the maximum achievable clinical result. 10.7448/IAS.15.6.18067 © 2012 Perno C; licensee International AIDS Society Published 11 November 2012 Keynote Lecture – KL3 Abstract Remarkable advances have been achieved over the past decade in confronting the global HIV epidemic. By the end of 2010, 6.5 million persons living with HIV had initiated antiretroviral therapy in low and middle-income countries, the majority in sub Saharan Africa. Of the total of 2.5 new HIV infections that occurred in 2010, 1.9 million occurred in sub Saharan Africa. Nonetheless, 22 countries in sub Saharan Africa have experienced a decrease in HIV incidence. These remarkable achievements have involved a transformation of fragile health system. Examples include new models of care, task shifting, infrastructure enhancement, establishment of new data systems and mobilization of communities. However, many of the same countries where HIV is prevalent also confront other health threats including high maternal and child mortality, high rates of tuberculosis and malaria as well as a burgeoning non-communicable chronic disease threat. Addressing these health threats requires taking the lessons learned from the HIV response and adapting them to confront these threats. Through building on the foundation established, similar progress may be achieved in addressing these health threats while maintaining the momentum of the HIV response. 10.7448/IAS.15.6.18068 © 2012 El-Sadr W; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O111 Abstract Despite major advances in HIV therapy, the number of new HIV infections remains very high, even in high-income countries where resurgence among men who have sex with men (MSM) has been witnessed. New prevention strategies have therefore to be assessed in order to curb the incidence of HIV infection. Recent studies have explored the effectiveness of antiretroviral therapy (ART) for HIV prevention and have generally yielded encouraging results. ART has been used successfully to prevent mother-to-child transmission of HIV, HIV acquisition following occupational or sexual exposure to HIV (post-exposure prophylaxis), and more recently, to reduce the risk of HIV transmission within a serodiscordant couple by treating the HIV-positive partner (HPTN 052 study). Another possible use of ART in prevention is pre-exposure prophylaxis, where ART is taken by an HIV-seronegative individual before HIV exposure. This PrEP strategy has been validated in animal models and more recently assessed in clinical trials in humans. The results of six large efficacy trials of PrEP are now available, but results have been inconsistent. The use of tenofovir gel in women at higher risk in Sub-Saharan Africa has shown efficacy when given before and after sex in the Caprisa 004 study (reduction of 39% of the incidence of HIV), whereas no efficacy was shown with daily use in the VOICE trial. Similarly, daily oral PrEP with tenofovir or tenofovir and emtricitabine has proved effective in the Iprex trial in MSM (reduction of 42% of HIV incidence), in the Partners PrEP study (reduction of 67 to 75% in HIV incidence) and in the TDF-2 trial (reduction of 63% in HIV incidence), but not in the Fem-PrEP or the VOICE trials in women. There are many potential explanations for these apparently conflicting results, such as the populations in which these strategies have been assessed, the differential pharmacokinetics of ART in the male and female genital tracts and most likely the high level of adherence which is required to confer protection against HIV acquisition. These results have also generated a lot of controversy about the implementation of PrEP. Some think that the data are good enough to rollout PrEP in key populations at higher risk. Others think more research is needed before PrEP is implemented because of concerns around safety, emerging resistance, cost and change in sexual behaviour that might offset the benefit of PrEP. Safety is indeed a major concern in healthy individuals. New studies are underway to address these issues and are assessing PrEP regimens in open-label studies (Iprex-OLE in MSM), intermittent PrEP regimens to try to improve adherence, new ART classes and new modalities of drug delivery. PrEP is therefore a promising biomedical intervention that might be used in the near future in addition to current prevention methods to prevent HIV infection and help control the spread of this infection. 10.7448/IAS.15.6.18069 © 2012 Molina J M; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O112 Abstract Debate regarding “When to start” antiretroviral (ARV) therapy has raged since the introduction of zidovudine in 1987. Based on the entry criteria for the original Burroughs Wellcome (002) study, the field has been anchored to “CD4 counts” as the prime metric to indicate ARV treatment initiation for asymptomatic HIV-positive individuals. The pendulum has swung back and forth, based mostly on the efficacy and toxicity of available regimens. In today's world, several factors have converged that compel us to initiate therapy as soon as possible: (i) The biology of viral replication (1 to 10 billion viruses/day) screams that we should be starting early. (ii) Resultant inflammation from unchecked replication is associated with earlier onset of multiple co-morbid conditions. (iii) The medications available today are more efficacious and less toxic than in years past. (iv) Clinical trials have demonstrated benefit for all but the highest CD4 strata (>450 to 500 cells/µL). (v) Some cohort studies have demonstrated clear benefit of ARV therapy at any CD4 count, and almost all cohort studies have demonstrated no detrimental effects of early treatment. (vi) In addition to the demonstrated and inferred benefits to the individual patient, we now have a public health benefit of earlier intervention: treatment is prevention. Finally, from a practical/common sense perspective, we are talking about life-long therapy. Whether we start at a CD4 count of 732 or 493/µL, the patient will be on therapy for over 40 to 50 years! There does not seem to be much benefit in waiting, and there is likely to be significant long-term harm. Treat early! 10.7448/IAS.15.6.18070 © 2012 Saag M; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O113 Abstract It remains controversial whether and, if so, the extent to which antiretroviral therapy (ART) results in net benefit if used by HIV-positive persons with a high CD4 count, particularly those with early HIV infection. This controversy is primarily reflecting lack of solid evidence from randomized controlled trials. Currently published trials have compared early ART with initiation of ART below currently globally accepted thresholds for initiation (i.e. CD4 count at 350 cells/µL) and, hence, are unable to inform this discussion. Analyses on large observational studies that have attempted to address this question have shown inconsistent results; therefore, those results are considered low-quality evidence, as per the GRADE criteria used by, for example, WHO when formulating guidelines. In resource-constrained regions, not even observational data are available to inform this question. The START study is underway to answer this question. Data remain blinded, but START may show net harm from early use of ART; such a result would severely undermine use of ART as prevention in early HIV infection. Prescription of any type of medicine is guided by the principle of “do no harm” – that is, “the doctor should not prescribe medications unless s/he knows that the treatment is unlikely to be harmful.” Hence, the balance of risk/benefit to individuals versus prevention benefit is important to accurately determine, and current guidelines of generally initiating ART once the patient develops HIV-related symptoms or the CD4 count drops to levels around 350 cells/µL should be adhered to until further evidence has emerged. 10.7448/IAS.15.6.18071 © 2012 Lundgren J; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O114 Abstract Late presentation represents a major problem for patients with HIV infection. Actually, it should be made a distinction between late testers and late presenters since the strategies to reduce the percentage of these two groups of subjects could be different. Indeed, the first population is represented by individuals unaware of their serological status, while in the second case the problem is related to engagement and retention in care. Concerning the first population, it has been shown that most of the patients had been seen by their family doctor or admitted to hospital during the year before HIV diagnosis. Indeed, this is a relevant problem, and new strategies to increase the level of suspicion of HIV infection among doctors who are non-HIV specialists are needed, as testing in presence of indicator diseases, should be applied. Concerning the population of late presenters, American data showed a percentage of engagement in care ranging between 50 and 59%. These low percentages could be due to the American Health System, while in a public health system setting, the percentage of patients not engaged in care or lost to follow-up could be lower, even if still relevant. Another important factor that should be considered in both populations is stigma. Indeed, many patients that present late, either late testers or late presenters, are immigrants and have important cultural barriers to disclose their HIV serostatus to family members and friends. Obviously, all subjects unaware or refusing their HIV infection could potentially infect their partners. In conclusion, all efforts should be made to reduce the phenomenon of late presentation since these two populations represent an epidemiological problem not only for the prognosis of the single patient but also for the treatment as prevention strategy. 10.7448/IAS.15.6.18072 © 2012 Mussini C; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O121 Abstract As treatment for HIV infection needs to be used continuously and lifelong, issues concerning long-term outcomes, including those involving tolerability and safety of treatment, are gaining increasing importance. Although current combination antiretroviral therapy (cART) regimens are generally better tolerated than those in the early days of cART, treatment toxicity remains an important cause for discontinuation of (components) of treatment. Moreover, several of the potential toxicities of cART (including cardiovascular, metabolic, renal and bone toxicity) overlap with known ageing-associated co-morbidities. Given that our patient population with HIV is increasingly getting older as a result of the success of cART in reducing traditional HIV-associated morbidity and mortality, these co-morbidities are increasingly being seen and importantly influence patient management. Moreover, persons with HIV, in spite of having suppressed viraemia on cART seem to be at increased risk of the premature development of age-associated non-communicable co-morbidities, including cardiovascular, chronic kidney, liver and pulmonary disease, diabetes mellitus, osteoporosis, non-AIDS associated malignancies, and neurocognitive impairment. It has therefore been hypothesised that such individuals, despite effective cART, may be prone to accelerated ageing. The underlying pathogenesis is likely to be multifactorial and, apart from include sustained immune activation, both systemically and within the central nervous system. The presentation will review the current state of knowledge and investigation in this area. 10.7448/IAS.15.6.18073 © 2012 Reiss P; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O122 Abstract Despite ART scale-up, tuberculosis (TB) remains a leading cause of HIV-related deaths worldwide and much of this disease may remain unascertained. In patients receiving ART, TB incidence is highest during the first few months of treatment (many cases of which were prevalent disease missed by baseline screening) and long-term rates remain several-fold higher than background. We identify three groups of patients starting ART for which different interventions are required to reduce TB-related deaths. First, diagnostic screening is needed in patients who have undiagnosed active TB so that timely anti-tuberculosis treatment can be started. This may be greatly facilitated by new diagnostic assays such as the Xpert MTB/RIF assay and a novel point-of-care urine test for lipoarabinomannan (LAM). Second, patients with a diagnosis of active TB need optimised case management, which includes early initiation of ART (with early timing now defined by randomised controlled trials), trimethoprim-sulphamethoxazole prophylaxis and treatment of co-morbidity. Third, in high TB burden settings, all remaining patients who are TB-free at enrolment have high ongoing risk of developing TB and require optimised immune recovery (with ART ideally started early in the course of HIV infection), isoniazid preventive therapy and infection control to reduce infection risk. Further specific measures are needed to address multi-drug resistant TB (MDR-TB) and there are now new promising developments in antimycobacterial agents. Finally, in high burden settings, scale-up of all these interventions requires nationally and locally tailored models of care that are patient-centred and provide integrated health care delivery for TB, HIV and other co-morbidities. 10.7448/IAS.15.6.18074 © 2012 Lawn S; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O123 Abstract Globally over 50% of HIV-infected individuals are women. With the widespread use of HAART, we can expect women to have mortality rates approaching normal. Indeed, studies have shown that women may expect a slower disease progression than men following seroconversion; furthermore, it appears that female who injects drugs can live longer than their male counterparts. However, other studies from cohort analysis have reported worse outcomes in women. In essence, many studies are consistently underpowered to adequately address these questions. The proportion of women in clinical trials remains at 20 to 30%, with pregnancy potential being a major exclusion factor. Hence, many questions remain unanswered. Recent data suggest women are more likely to present late with a new AIDS diagnosis. Why this should be the case is not well understood. In addition, HIV-positive women should have the same access to reproduction health as their negative counterparts, but unfortunately many inequalities remain. Advise on contraception and fertility services are very variable across both the developed and developing world. Data are limited on the most appropriate use of contraceptives in the presence of HAART, the possible drug interactions and possible increased risk of HIV transmission. There remain significant differences in guidelines regarding prevention of mother-to-child transmission (MTCT) across Europe, and implications of stopping and starting HAART for MTCT have not been adequately addressed. The mode of timing of delivery, and the effect of length of time of ruptured membranes on this decision is also contentious. Further issues relate to the desire for HIV-positive women to breastfeed in the setting of HIV viral suppression, where some guidelines now support women in this situation and others categorically would inform child protection authorities. Finally as women age it is more difficult to separate the effect of the menopause and its symptoms from the increased HIV-related cardiovascular and bone fracture risk. This presentation aims to discuss key issues which conflicting or inadequate data fail to resolve. 10.7448/IAS.15.6.18075 © 2012 Mulcahy F; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O131 Abstract Life expectancy (LE) is an important indicator of health used widely by government and healthcare agencies to monitor trends over time and to determine resource allocation, as well as by insurance companies and pension providers. LE of the HIV-positive population has increased dramatically since the introduction of combination antiretroviral therapy (cART); indeed, it is now believed that LE may be similar to that of the general population in some subgroups. There are, however, specific subgroups in which LE remains substantially impaired. The impact of HIV and of cART on mortality may be expressed in several ways. LE itself provides an estimate of the average additional number of years that an individual would be expected to live beyond a particular age. However, the detrimental impact of HIV may also be described in terms of the number of years of life lost or the gains in LE if HIV were to be eliminated as a cause of morbidity in the population. My presentation will start with a description of the different methods that researchers have used to describe the mortality outcomes of those with HIV, and the impact of cART on these. I will then consider how LE in the HIV-positive population has changed over time and will describe the impact of demographic factors (e.g. gender, age, ethnic group) on LE. To investigate the circumstances under which LE may return to normal levels, I will also consider the potential impact of timely diagnosis and linkage into care, continued engagement with care, optimal initiation of cART and maintenance of viral suppression on LE. Finally, I will discuss some of the limitations of the approaches used to estimate LE, with particular emphasis on the confounding effects of lifestyle and behavioural factors when making any comparison with LE in the general population. 10.7448/IAS.15.6.18076 © 2012 Sabin C; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O132 Abstract Purpose of the study Combination antiretroviral therapy (cART) has greatly improved the life expectancy of people living with HIV (PLHIV). A series of cohort studies have predicted near-to-normal life expectancies for PLHIV receiving cART but have not considered the impact of multi-class resistance on long-term survival. Our study aims to project the future life expectancy of PLHIV in a resource-rich setting in the context of the currently available antiretroviral treatments. Methods Patient antiretroviral treatment data, including time on each regimen until treatment failure, were sourced from an observational cohort of 3434 predominantly male (94.2%) PLHIV in Australia over the period 1997 to 2010. These data were analyzed in an individual-based mathematical model to calculate the time until exhaustion of all treatment options and the expected impact on HIV-associated mortality. Standardized mortality ratios were used to simulate expected survival before and after treatment exhaustion. Summary of results The model estimated that the median time until exhaustion of currently available treatment options is 43.4 years (interquartile range = 31.4 to 58.6 years). However, the model predicts that 10% of PLHIV will use up all currently available cART options after just 22.6 years. The figure shows the survival proportions of males from age 20 years in four mortality scenarios: (1) the general population mortality rate; (2) the mortality rate in PLHIV as currently measured (without considering exhaustion of currently available treatments); (3) mortality rate in PLHIV considering additional mortality due to limited cART options; and (4) mortality rate if no cART is available. PLHIV who start currently available cART regimens at age 20 years are expected to live to a median of 64.7 (95% uncertainty bound (UB) = 61.8 to 69.3) years of age, when adjusting for treatment option exhaustion. This is a substantial improvement on no cART (median survival to 27.6 [95% UB = 27.2 to 28.1] years of age) but is lower than the expected life expectancy (82.2 years of age) of an HIV-negative male in the general population. The gap between life expectancy among PLHIV and the general population is greater for those infected at younger ages. Conclusions As treatment options are exhausted in the coming years, a substantial difference in life expectancy between PLHIV and the general population is expected, particularly for people who acquire HIV at a younger age or who are currently highly treatment-experienced. 10.7448/IAS.15.6.18077 © 2012 Jansson J et al; licensee International AIDS Society Published 11 November 2012 Oral Abstract – O133 Abstract Life expectancies (LEs) of patients in UK Collaborative HIV Cohort (UK CHIC) stratified by CD4 count at start of antiretroviral therapy (ART) have been estimated [1] but not gains in years of life in response to ART. We estimated LE associated with attained CD4 count and viral suppression at different durations of ART. Patients in UK CHIC aged > 20 years who started ART in 2000 to 2008 (excluding person who injects drugs) were followed to end of 2010. All-cause mortality was ascertained from clinic notes and by linkage to national records. We used the nearest CD4 count before ART and the last in each of years 1 to 5 of ART and determined whether patients were virally suppressed (HIV-1 RNA < 400 copies/mL) in the past year for those remaining under follow-up. Poisson models were used to estimate mortality rates by sex, age, latest CD4 count (<200, 200 to 349,≥350) and viral suppression for each duration of ART. Abridged life tables were constructed from age-specific mortality rates to estimate LE for ages 20 to 85 years. Results are presented as the average number of years that will be lived after exact age 35 years. A total of 17,021 patients started ART from 2000 to 2008 of whom 708 (4.2%) died; 3956 (23%) were lost to study follow-up. There was no difference in mortality between those with attained CD4 350 to 499 and ≥ 500. On starting ART, male LE at exact age 35 was 36, 44 and 42 (female LE 38, 46 and 44) years for attained CD4 < 200, 200 to 349,≥350, respectively; after 5 years on ART, it was 22, 42 and 46 (female LE 27, 46 and 51) years, respectively. Only 17% of patients had CD4 ≥ 350 at ART start, compared with 78% of patients on ART for > 5 years. The difference in LE between suppressed versus unsuppressed patients was around 11 years. The figure shows that both CD4 count and viral suppression contribute to changes in LE. Male patients that increased their CD4 in the 1st year of ART from < 200 to 200–349 or ≥ 350 gained 6 and 11 years of LE to 42 and 48 years, respectively, with similar rises for women. Overall, LE was 4 years greater for those on ART for > 5 years compared with those starting ART. Individuals that attain viral suppression and a CD4 count > 350 within 1 year of ART start have a normal LE with 35-year olds estimated to live to over 80 years on average. LE in patients with CD4 count < 200 beyond 5 years on ART drops by 15 years. Estimated LE may be biased by under-ascertainment of deaths, missing CD4 measurements and extrapolation beyond available data. 10.7448/IAS.15.6.18078 © 2012 May M et al; licensee International AIDS Society Published 11 November 2012 Reference 1.May M, Gompels M, Delpech V, Porter K, Post F, Johnson M, et al. Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study. BMJ. 2011; 343: d6016. http://dx.doi.org/10.7448/IAS.15.6.18078CrossrefPubMedWeb of Science®Google Scholar Oral Abstract – O141 Abstract Clinical pharmacokinetic data on antiretroviral drugs are scarce in African HIV-1-positive patients. Most available pharmacokinetic data are derived from ethnically distinct Caucasian research volunteers. This presentation will focus on the clinical pharmacokinetics training and research outputs of an HIV Research Trust scholarship recipient in Uganda. The work hi
Referência(s)