HIV Drug Therapy in the Americas Congress, 13 – 15 June 2013, São Paulo, Brazil

Antiretroviral therapy (ART) can sustain suppression of plasma viremia for years. However, if therapy is interrupted, there is a rapid resumption in viremia. Therefore, HIV‐1 has the ability to persist in the face of potent ART. Identifying the mechanism through which HIV‐1 persists in infected individuals on suppressive therapy is central to the goal of curing infection in these individuals. For this reason, research is focused on establishing tools with which to probe the reservoirs that persist in aviremic individuals as well as clinical protocols with which to perturb those reservoirs. How we measure viral reservoirs in aviremic patients and, as a consequence, how we gauge the impact of treatments on those reservoirs is a contentious issue. Most attention has focused on the role of latently infected T‐cells in viral persistence and clinical strategies are geared towards purging of these reservoirs. However, other factors may be contributing to viral persistence including residual viral replication and establishment of non‐T‐cell reservoirs. In addition, although ART significantly improves health outcomes for the patient, several markers of immunopathogenicity persist in the face of effective viral suppression and drive comorbidities. The underlying cause of ongoing pathogenicity in the face of effective ART is unclear. Studies examining the impact of treatment intensification on markers of viral pathogenicity will be discussed.


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Research on persistence and pathogenesis under ART Introduction: Antiretroviral therapy (ART) can sustain suppression of plasma viremia for years. However, if therapy is interrupted, there is a rapid resumption in viremia. Therefore, HIV-1 has the ability to persist in the face of potent ART. Identifying the mechanism through which HIV-1 persists in infected individuals on suppressive therapy is central to the goal of curing infection in these individuals. For this reason, research is focused on establishing tools with which to probe the reservoirs that persist in aviremic individuals as well as clinical protocols with which to perturb those reservoirs. How we measure viral reservoirs in aviremic patients and, as a consequence, how we gauge the impact of treatments on those reservoirs is a contentious issue. Most attention has focused on the role of latently infected T-cells in viral persistence and clinical strategies are geared towards purging of these reservoirs. However, other factors may be contributing to viral persistence including residual viral replication and establishment of non-T-cell reservoirs. In addition, although ART significantly improves health outcomes for the patient, several markers of immunopathogenicity persist in the face of effective viral suppression and drive comorbidities. The underlying cause of ongoing pathogenicity in the face of effective ART is unclear. Studies examining the impact of treatment intensification on markers of viral pathogenicity will be discussed. 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 STD 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 proven 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 underway 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 HIV infected people 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. Latin America is globally recognized for achieving high coverage of antiretroviral treatment. Virtually all countries in the region have been able to achieve this important goal by offering universal access to antiretroviral drugs through their public health systems, despite the fact that antiretrovirals are available for these countries at relatively high prices, compared to other low-and middle-income countries. However, even though it would be fair to say that the access problem has been solved in the region, there are other important challenges that need to be strategically addressed. Both treatment and prevention programmes in our countries urgently need to be optimized, which means that although the infrastructure and capacity to implement highly effective programmes already exist, but the challenge now is to increase quality and efficiency. During this presentation, I will address some of the aspects, both programmatic and economic, that appear to be the most pressing ones requiring our attention, and also discuss some of the alternatives available to us toward improving the performance of our programmes. On the treatment side, I propose that there are likely large potential gains in improving timeliness of treatment initiation and efficiency of treatment regimes. On the prevention side, significantly improving testing efforts and increasing their coverage is probably a good measure toward increasing the health gains of our efforts. Using evidence to address these issues is key, and I wish to put to you that not only have we not done it enough in the past but that we also urgently need to generate evidence upon which to base our decisions. Most of the scientific evidence on the prevention realm comes from Africa. We need to be more creative and innovative and rigorously evaluate approaches to improve access, quality and efficiency. The collaborative international effort to provide universal access to HIV care and effective antiretroviral therapy (ART) has reached a critical time point. The global economic downturn, changing donor priorities and competing priorities in the health sector threaten the capacity of various agencies to maintain support for the continued scale-up of access toward the UN General Assembly-agreed target of 15 million people with HIV/AIDS receiving ART by 2015. We now know that treatment acts as prevention by reducing the infectiousness of treated individuals. It is now necessary to review the elements of the successes and challenges to date, in order to be able to best use finite resources. These elements include efforts to optimize the delivery of HIV care, including ART, in low-and middleincome countries (LMIC) and the emergence of new agents and drug classes, which have simplified HIV treatment and made broader successful management more achievable. Recent studies have indicated that earlier commencement of HIV therapy is beneficial, leading to changes in the recommended ART initiation threshold in LMIC to B350 CD4 T cells. Forthcoming revised WHO guidelines are anticipated to raise this threshold. Studies currently under way are investigating approaches to second-line ART in LMIC. The results from these studies will better inform the roll-out of effective secondline therapy. In addition, the financial cost of ART makes optimization of dosing an important consideration in LMIC, in order to maximize effectiveness while limiting costs. ART monitoring is also an important priority in LMIC. Efforts to develop simple and reliable technologies that can provide rapid results in the field are underway. In the meantime, a number of recent studies in adults and children point to the way forward and the best use of resources. The final priority is operational optimization, to ensure adequate service delivery. Although the challenges in LMIC are substantial and evolving, considerable inroads have been and are being made into optimizing HIV treatment and its delivery, which is crucial in reducing the global impact of the disease. This abstract is modified from an abstract provided by David Cooper, University of New South Wales, Sydney, Australia, when presented as the Lock Lecture at HIV Drug Therapy in Glasgow, November 2012. There currently are 27 antiretroviral drugs approved for the treatment of HIV infection. In choosing the optimal initial regimen, a number of factors should be considered: antiretroviral activity (HIV RNA, CD4 cell, and clinical responses); durability of responses; baseline drug resistance; tolerability and both acute and chronic side effects; convenience (number of pills, dosing interval, food/ fasting requirements); preserving future treatment options; patient's stage of HIV disease, concomitant illnesses and medications (and drug-drug interactions); access; and cost. The optimal initial regimen is one that is individualized to the specific patient's situation. Current preferred initial regimens include two nucleoside analogues (NRTI) combined with either a non-nucleoside analogue (NNRTI), a boosted protease inhibitor (PI), or an integrase inhibitor (II). Onepill, once-daily combination regimens have proven particularly popular with patients and providers alike. The most common initial regimen worldwide is two NRTI ' an NNRTI. In the event of virologic failure of an initial regimen, multiple causes of failure should be assessed, including: adherence; drug resistance; use of less potent antiretroviral regimens; drug levels and drug-drug interactions; and theoretically, tissue reservoir penetration (central nervous system, genital tract). Of course, any or all of these reasons may be important and the challenge is to address the probable cause(s) of failure and address them in choosing the next regimen, to ensure success. Genotypic drug resistance testing is indicated in the assessment of first (or second) virologic failure and can help optimize the selection of the next regimen. Genotypic and phenotypic testing is recommended following failure of multiple regimens. A common sequence of regimens is two NRTI and an NNRTI, changing to two NRTI ' a boosted PI. The availability of drugs with activity against drug-resistant viruses (e.g. newer NNRTIs and PIs) and new classes of drugs (e.g. integrase inhibitors, CCR5 antagonists) offers additional options for constructing successful subsequent ART regimens. HIV resistance to ARV therapy is an unwanted consequence of HAART as it limits future options. The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up, without proper treatment monitoring and drug availability, could compromise the effectiveness of national HIV treatment programmes. Compared to developed countries, most of Latin America do not perform resistance assays before starting ARV treatment and after first line failure, having more resistance as a consequence in some cases and the need for more expensive salvage treatments. Some countries in the region do not have access to resistance tests due to cost and lack of infrastructure. The presentation will include data on the limited increase of transmitted resistance over time in the region compared to other developing countries, especially in Africa, as well as the prevalence of secondary resistance in first line failure and multiexperienced patients, with remark on specific issues with non-B subtypes. The elevated cross-resistance to the entire nucleoside analogue group in countries still using thymidine compounds in first line treatment will be stressed. Moreover, it will include the big limitations for resistance assay interpretations and performance in low level viraemia in Latin America as well as the excellent results of using resistance committees in the optimization of available assays as in the prescription of newer drugs.
Introduction: Third-line antiretroviral drugs (ARV) are now indicated for the treatment of multi-resistant HIV/AIDS patients in virological treatment failure. Although being the last and highly effective line of defence, they are almost not present in the South because of their prohibitive cost. Therefore, Brazil, where these drugs have been adopted since 2005, constitutes an ideal laboratory to study nextgeneration drugs inclusion.  (2010), all patented and imported at very high prices. Over time, however, a lower purchase price is observable (see Table 1). Thus, the price of darunavir (300 mg tablet) decreased by 19.6% between 2007 and 2009; enfuvirtide (108 mg vial) by 19.3% between 2007 and 2009; raltegravir (400 mg tablet) by 12. 8% between 2008 and 2009. In 2008, only three third-line ARVs consumed together approximately 26% of the total budget for the acquisition and distribution of National HIV/AIDS Program (see graphic 1). In 2009, the situation becomes even more significant: almost 40% of the total budget were spent with these three ARVs (see graphic 2). Discussion and conclusion: Brazil is considered a middle-income country and therefore cannot be benefited with the low prices offered to low-income countries. However, as ARVs purchases are performed centrally, we expected a greater bargaining power by the Ministry of Health. In practice, there are price reductions when increasing quantity purchases, but this does not seem sufficient to ensure financial sustainability of the rising third-line ARV Program. Today, third-line ARVs are distributed to 5,000 patients (from the universe of 190,000 patients that are currently receiving antiretroviral therapy) and consume 40% of the total ARV procurement. This scenario seems daunting given the strategies of ARV treatment, which already consumes two percent of the total ministerial budget. In fact, it is essential to continue negotiations with the pharmaceutical industry; furthermore, we must not forget the investment in Entecavir and telbivudine also have potential anti-HIV activity and therefore should only be administered with highly active antiviral therapy against HIV. Adefovir may be prescribed as monotherapy for hepatitis B alone, although it is less potent than other but at the dose utilised there is no activity against HIV. It is essential that all individuals with hepatitis B are monitored for the development of hepatoma due to an increased frequency of development and progression of this tumour type in those co-infected with hepatitis B. HIV and hepatitis C co-infection is common due to shared routes of transmission and similar geographical distributions. Although hepatitis C does not impact on the prognosis of HIV disease, HIV is associated with more rapid progression of fibrosis and hence hepatic complications associated with hepatitis C infection. Globally there is an epidemic of acute hepatitis C in HIV-infected homosexual men, which is fuelling the numbers who are co-infected. Hepatitis C infection is associated with complications associated with HIV disease including a higher risk of cardiovascular disease, diabetes, renal dysfunction, and osteoporosis with bone fractures. The development of the protease inhibitors telaprevir and boceprevir for the treatment of hepatitis C has translated into improvements in the outcome of therapy in the hepatitis C mono-infected population; although only small studies are available, the results in the co-infected population appear to be similar. In addition, second generation protease inhibitors have been associated with early response rates, even higher than with telaprevir and boceprevir in the co-infected populations. The generation of interferon-sparing regimens is also of great promise, and clinical studies have recently commenced in the HIV-infected population. It is essential that individuals with HIV are tested for hepatitis B and for hepatitis C and vice-a-versa, and that these are repeated frequently, so that individuals who are or do become co-infected can benefit from the positive outcomes associated with these new treatments. , or 10 days of rilpivirine (RPV, 25 mg QD, n 0 17, fed), darunavir/ritonavir (DRV/r, 800/100 mg QD, n 0 19, fed), or raltegravir (RAL, 400 mg BID, n 0 19, fasted). Geometric means ratio% (GMR%, combination vs alone) of PK parameters AUCinf and Cmax for SOF and GS-331007 (circulating nucleoside metabolite of SOF), or AUCtau, Cmax, and Ctau for TFV, FTC, EFV, RPV, DRV/r, or RAL were evaluated against a predetermined 70Á143% equivalence boundary. Safety assessments were conducted throughout the study.
Results: A total of 16 and 17 subjects completed the ATR and RPV cohorts, respectively, and 18 subjects completed the DRV/r and RAL cohorts. The most frequent adverse events were dizziness, headache, diarrhea, nausea, and constipation, predominantly during ATR dosing. All but one event were mild and most were consistent with known EFV adverse events. Overall, SOF was well tolerated with very few treatment-emergent events during the administration of SOF with ARVs. Co-administration of HIV ARVs and SOF did not result in clinically significant changes in SOF and/or GS-331007 exposure. ATR slightly decreased SOF and GS-331007 Cmax (Â20Á23%), RPV, DRV/ r, and RAL modestly increased SOF exposure by 21 to 45% with no effect on GS-331007. SOF slightly increased TFV Cmax (Â25%), modestly decreased RAL AUCtau (Â27%) and Cmax ( Â43%), but did not affect RAL Ctau, and had no other effect on PK parameters of FTC, TFV, EFV, RPV, or DRV/r. 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. Human immunodeficiency virus (HIV) infection has become a chronic long-term manageable condition. Subsequently with ageing of this population, comorbidities such as renal impairment are becoming more prevalent. Kidney diseases are emerging as significant causes of morbidity and mortality with older age, black ethnicity, hypertension, diabetes, low CD4' cell count, HCV co-infection and high viral load remaining important risk factors for kidney disease in the HIVinfected population. HIV-associated nephropathy (HIVAN) is an uncommon but important cause of renal disease whose outcome can be improved by HAART. Having started treatment, HIV-infected individuals require lifelong antiretroviral medication but longterm data on the renal toxicity of HAART are limited. HIV affects the kidney directly or indirectly by drug-related effects that are directly nephrotoxic or lead to changes in renal function by inducing metabolic vaculopathy and renal damage. Historically, indinavir, mainly through renal crystal and stone formation, affected renal function but more recently cohort data have implied that atazanavir and lopinavir are also linked to renal dysfunction through a similar mechanism. Randomized clinical trials and post-marketing data supported the renal safety of tenofovir in relatively healthy HIVpositive individuals. However, overall tenofovir use is associated with 0.5Á2.5% risk of acute kidney injury (AKI). The most frequent mechanism of tenofovir-induced kidney failure is thought to be tubular necrosis due to mitochondrial toxicity. Other mechanisms by which antiretroviral drugs cause renal impairment are complex and not completely understood. Effects on drug transporters leading to unfavourable drug interactions have been proposed. The increase in drug levels of tenofovir when given with ritonavir may be part of the reason why regimens of boosted PIs and tenofovir are associated with abnormalities in eGFR. Calculations estimating clearance of creatinine are widely accepted as the best measure of kidney function when using a 24-hour collection of urine. As urine collections are rarely performed, formulae to calculate eGFR using serum creatinine, demographic, and other factors have been developed. Interpretation of these formulae is complicated, and distinguishing normal from abnormal function in the individual patient is inherently difficult. The most used formulae are the CockcroftÁGault formula, the Modification of Diet in Renal Disease (MDRD) formula, or The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. All use serum creatinine as the basis of their calculation and hence any tubular contribution to plasma creatinine levels are included in their estimation of GFR. None of these equations have been systematically validated in HIVinfected patients. The evaluation of glomerular filtration using these formulae which include plasma creatinine to estimate GFR do not take into account that 10Á20% of creatine is secreted through the tubules and the proportion rises with worsening glomerular function. The actual or real glomerular filtration rate (aGFR) is difficult to measure requiring isotopic or intravenous infusions such as iohexol or detailed imaging. Another reason for the eGFR to become abnormal when the aGFR remains unaffected is the inhibition of tubular enzymes. Blocking enzymes responsible for the tubular secretion of creatinine will lead to rises in serum creatinine and a fall in eGFR. This can lead to physicians believing that drugs have caused renal impairment but actually there is no change in aGFR. Dolutegravir by inhibiting OCT 2 and ritonavir and cobicistat by inhibiting MATE-1 renal transporters can all show this phenomenon with median falls in eGFR after starting these compounds of around 10-15 ml/min. These effects usually reach a steady state by two to four weeks. Physicians need to be aware of this and be able to differentiate between the expected changes in eGFR due to any enzyme inhibition and any changes due to true renal disease. Measuring tubular dysfunction is problematic and rely on increases in urine creatinine protein ratios, normoglycemic glycosuria, the presence of increased amounts of low-molecular-weight proteins such as b2-microglobulin or light chains, aminoaciduria, and inappropriate amounts of uric acid or phosphorus, coupled with a reduced phosphate re-absorption rate. It has been suggested that urine dipstick for glucose and protein and serum phosphate be used as monitoring tools to trigger further investigation of tubular dysfunction. With the ageing of the HIV population and the use of co-medications that could alter renal function, the issue of monitoring and interpreting and understanding laboratory data to safely prescribe antiretrovirals will come even more into focus.
The introduction of highly active antiretroviral therapy resulted in the dramatic reduction of HIV/AIDS-associated mortality and the redefinition of HIV infection as a chronic condition. Nowadays, life expectancy of new diagnosed HIV individuals is approaching that of the uninfected population. Therefore, HIV management is now faced by challenges associated with age-related comorbidities, in particular cardiovascular disease (CVD). It was suggested that HIV individuals are at higher risk of developing CVD compared with the general population, which can be explained by several factors: a) HIV individuals have a higher prevalence of smoking and other unhealthy lifestyle behaviours, b) some antiretroviral drugs have been linked to direct cardiovascular risk due to their effect on lipids or other not well-understood effects, and c) HIV might additionally contribute both directly or indirectly to a higher cardiovascular risk. Uncontrolled HIV viraemia is usually associated with chronic inflammation, chronic immune activation and immunosenescence, which some authors have defined as an ''accelerated ageing'' status. As the HIVpositive population continues to age, and HIV infection among older people is not an uncommon phenomenon, the risk of CVD will continue to increase. However, opportunities for preventive care and screening for and treatment of CVD are frequently missed. Case management and integrated care can help them confront the physical and psychosocial aspects of the disease and reduce marginalization and the dual stigma of both ageing and HIV. Within the last decade, the HIV epidemic amongst women has been steadily growing in the Americas, representing in some areas almost half of HIV-infected individuals. Although biological factors determine a higher vulnerability to HIV infection in women other elements seem to play as major determinants in this increasing dynamic of the HIV women's epidemic. There are epidemiological factors that are shared among HIV-infected women in different countries: belonging to minority groups, being less educated, exposed to domestic violence, high rates of poverty and difficult access to health care. These same factors hinder diagnosis and HIV care, even in countries where access to treatment is universal. Opportunities for early HIV-diagnosis are also limited; only during pregnancies in countries with MTCT prevention programmes; for most women HIV serology is performed when a partner or a child has been diagnosed, or when they arrive severely ill to a hospital. Care of HIV-infected women needs to address genderrelated health problems, particularly HPV co-infection. As patients survive longer with HAART, other health problems of ageing women need also to be surveyed and screened: osteoporosis, other gynecologic malignancies and metabolic disturbances among them. MTCT programmes have achieved enormous success in high-income countries. Although enormous efforts have been made to extend this success to low-and middle-income countries, there is still a wide lag in many countries, and children born HIV-positive are still counted in their hundreds in Latin-America. This field needs further advocacy to achieve universal MTCT prevention. Treatment of HIV/AIDS: While an outright cure or a preventive vaccine for HIV/AIDS remains elusive, remarkable advances in HIV treatment have been achieved over the past two decades. Most significant among these advances is the development of highly active antiretroviral therapy (HAART). Two international clinical trials presented at the 1996 International AIDS Conference in Vancouver, served as the cornerstone for the emergence of triple therapy regimens based on the use of two nucleosides plus either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (aka highly active antiretroviral therapy or HAART) as the new standard of care [1Á3]. In each case the novel triple therapy regimen used among treatment-naïve individuals fully suppressed HIV replication and, therefore, rendered the number of viral copies present in a patient's blood undetectable. As a result, the CD4 cell counts recovered and the disease was placed into a long-term remission. In the province of British Columbia (BC), within three years of the implementation of HAART, the BC Centre for Excellence in HIV/AIDS (BC-CfE) documented an 85% reduction in HIV/ AIDS mortality among patients engaged in treatment. Similar results have been observed in other resource-rich environments, and more recently in resource-limited settings, where HAART has become available. Treatment as prevention: More recently, evidence has accumulated that the viral load suppression achieved by HAART has a marked impact on decreasing HIV transmission. Already in August 2006, we proposed in a viewpoint article in The Lancet that the expansion of HAART coverage to all those in medical need would represent a key strategy to dramatically curb HIV/AIDS morbidity and mortality, as well as HIV transmission [4]. We further suggested that such strategy would be potentially cost-averting [5]. Evidence to support the impact of HAART on HIV transmission can be readily found in vertical transmission studies where it has led to the near complete prevention of transmission of HIV from the infected mother to the newborn. Similarly, among sero-discordant couples (one infected and one uninfected partner) transmission is a direct function of the level of plasma HIV viral load in the infected member of the couple: the more HIV is present in blood, the more virus is present in sexual fluids and therefore the greater the risk of HIV transmission [6]. HIV viral load in plasma and consequently in sexual fluids are effectively decreased to undetectable levels with HAART, thereby HAART dramatically reduces the risk of sexual HIV transmission. We have also shown that HAART can similarly prevent HIV transmission among injection drug users [7]. These results have now been independently validated within the ALIVE Cohort in the US [8]. More recently, at the population level, we have documented that expansion of HAART uptake between 1996 and 2010 has been associated with a greater than 65% decrease in HIV new diagnoses in BC [9]. Of note, this has taken place against a background of stable or rising sexually and blood-borne infections in the province. As a result, the provincial government has committed to further expand outreach efforts to maximize HIV testing and facilitated HAART access in BC, this initiative is known as Seek and Treat for Optimal Prevention of HIV/AIDS in BC (STOP HIV/AIDS in BC). The BC-CfE's proposal in support of ''Treatment as Prevention'' was initially regarded as controversial; however, this notion has gained the support of the international community, including the International AIDS Society and President Clinton in 2008 and Michel Sidibé, the Executive Director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), shortly thereafter. In January 2009, investigators based at the World Health Organization (WHO) AIDS programme published a paper in The Lancet, which independently verified the potentially critical role of ''Treatment as Prevention'' in the control of the epidemic [10]. More recently, HPTN 052 -a prospective randomized trial -provided definitive and compelling confirmatory evidence of the efficacy of ''Treatment as Prevention'' among sero-discordant couples [11]. HPTN 052 showed an impressive 96.3% decrease in the risk of HIV transmission with immediate HAART. Of note, immediate HAART was also associated with a 30% decrease in the combined endpoint of disease progression and death, and an 83% reduction in the incidence of extra-pulmonary tuberculosis. The latter results further galvanized international attention towards the key role of ''Treatment as Prevention'' for the control of the HIV epidemic. Indeed, US Secretary of State Hilary Clinton pledged the support of the US administration towards re-profiling PEPFAR efforts to emphasize the role of ''Treatment as Prevention'' and this was echoed by US President Obama during his speech on 1 December 2011, and on 23 December 2011, Science Magazine named ''Treatment as Prevention'' as the scientific breakthrough of 2011. It is clear that expanding access to HAART is highly effective in preventing morbidity and mortality among HIVinfected individuals, and secondarily it prevents HIV transmission. The data is conclusive and compelling. The anticipated release of the revised 2013 WHO treatment guidelines in July 2013 will markedly expand HAART eligibility globally [12]. The challenge remains to secure the necessary political will to fully renew WHO guidelines and, thus, implement the ''Treatment as Prevention'' strategy. An AIDS & HIVfree generation is within reach, however, this will not be attained if we fail to fully capitalize on the promise of ''Treatment as Prevention''.  (6) The International AIDS conference held in Vancouver in 1996, where modern HAART was born, was held under the motto ''One world, one hope''. Unfortunately, the world is falling short of this goal. Albeit it is encouraging that eight million people living with HIV in low-and middle-income countries have started antiretroviral treatment since 2001 Á people that would probably have died otherwise Á millions of people living with HIV still lack access to treatment and care. Many thousands of women, men and children continue to die as a consequence of our failure as a global community. Therefore, we need to plan aiming to honour the commitments and keep the promises made several times in different high level meetings, conferences and in an incredible number of declarations, papers and documents. As of today, ARV guidelines in so-called rich countries are not matched by WHO guidelines and several local countries recommendations. Of note these differences are not limited to the ''When to start'' question, but also include the list of preferred drugs, the recommended monitoring tools and the management of co-morbidities. In the era of treatment as prevention, the benefits of HAART expansion are no longer limited to the individual and has become a strategic public health tool in the struggle against HIV/AIDS. So, the gap between rich and poor countries' guidelines becomes even more unfair and painful. The world needs to move ahead and make the goal of ''One world, one hope'' a reality. Infectious agents that are endemic to specific geographic regions provide the clinical syndrome of AIDS with unique clinical and epidemiologic characteristics often not well recognized in different publications. In Latin America and the Caribbean, the infectious agents that play significant roles in the HIV epidemic in certain geographic areas are Histoplasma capsulatum, Leishmania sp, Trypanosoma cruzi, Coccidiodes imitis, Paracoccidioides brasilensis, Mycobacterium bovis, and some intestinal parasitic infections. Even though these infections are well known locally, there are significant knowledge gaps regarding the clinical presentation and epidemiology of these infections when present in HIV-infected patients. A review of the existing information on the topic will be presented. Implications for clinical management, research questions, and the challenge they represent to the health systems in the region will be discussed. Occurrence of these infections in the context of the immunosuppression associated with HIV infection accounts for the most widely recognized clinical and epidemiologic consequences. However, the increasing importance of chronic noncommunicable diseases in HIV-infected patients may also contribute to the unique challenges posed by these infections. Such may be the case of chronic Trypanosoma cruzi infection and cardiovascular diseases present in HIV-infected individuals. Transgender women are disproportionately affected by HIV, with prevalence and incidence rates consistently found to exceed those of men who have sex with men (MSM). Of particular concern are prevalence rates of over 50% found among young transgender women of colour. Despite this, the medical and psychosocial needs of transgender persons remain largely unmet, and few culturally appropriate and targeted HIV-prevention interventions exist for this population. This presentation will review the structural factors, including stigma, discrimination, and criminalization, as well as individual level factors, that lead to elevated HIV risk. These factors also negatively impact on access to medical care and affect all points of the HIV treatment cascade. Innovative evidence-based strategies that have been successfully implemented among transgender women, resulting in greater uptake of HIV testing, engagement, and retention in care will be described. Social determinants of health are factors which can be changed and controlled by policy and are largely responsible for the differences in the health outcomes in diverse populations and groups. This framework provides to explain health inequities and the impact of social injustice in health. In this presentation, the social determinants of health framework will be used to describe the impact of the socioeconomic and political contexts on HIV transmission risks in different populations. Particular attention will be placed to the impact of these social determinants in framing HIV-related inequities and vulnerability. Examples from prisoners and other populations in Caribbean Region will be used to describe the impact of social determinants of health on selected HIV-related outcomes including access and retention in care. Strategies and interventions to reduce inequities and address vulnerabilities associated with HIV/AIDS will be discussed. By 2010, Latin America and the Caribbean achieved 63% antiretroviral therapy (ART) coverage for HIV-infected patients although continuing barriers to HIV testing, ART initiation, and adherence remain. The region has a high rate of late ART initiation (LAI) associated with increase in early mortality, cost of care, and risk for HIV transmission. LAI is linked to high rate of both late HIV testing (LHT) and late presenters (LP), defined as starting ART ]6 months after HIV diagnosis. Barriers to HIV testing include lack of access to testing centres and poor service quality. Stigma plays a significant role for LHT and LP. Even with significant dissemination efforts in the public realm about HIV, individuals continue to underestimate their vulnerability to risk. Male gender, older age, lower socio-economic status, and external locus of control are characteristics of LP. Once patients are diagnosed with HIV, they face high rates of attrition prior to ART initiation. Absence of linkage of HIV testing centres to ART facilities, cost and logistics, such as clinic co-payments, transportation expenses, lack of nutritional support, and long waiting times are significant barriers to ART initiation and ongoing care. There is evidence that waived clinic fees, nutritional supplement, faster ART initiation, transportation subsidies, and early tracking for patients who miss visits may significantly decrease the rate of LP and LAI, improve retention in care, and adherence to ART. Further efforts to decrease barriers to HIV testing, ART initiation, and adherence will be critical to reach the goal of HIV universal treatment.

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Missed opportunities and late diagnosis in HIV infected Mexican women Introduction: Social factors increasing vulnerability to HIV in women hinder healthcare and early HIV diagnosis. Prevention efforts in countries with concentrated epidemics focus mainly in MSM and do not reach women at risk. We evaluated a sample of recently diagnosed HIV Mexican women to describe diagnosis circumstances, frequency of late diagnosis and factors associated with vulnerability. Materials and methods: Interviews were conducted on Mexican women from 2 large HIV care centers in Mexico City between January 2009 and November 2012. Information on sociodemographic data, partners, risk behaviour, history of physical/ sexual violence, HIV diagnosis circumstances and access to medical and prenatal care was obtained. Clinical information was taken from medical records. Results: 152 women were included (24% of total diagnosed in the period in both centers). Interviews were done to 122 women. Median age at diagnosis was 33 (17Á75). Maximum level of education was primary school in 42 (30%), 14(9%) were illiterate. A median of 3 lifetime sexual partners (1Á300) was reported. A third had their first pregnancy as teenagers. History of physical violence and sexual abuse was reported by 52% & 38%, respectively. In 85 (70%), likely source of infection was a stable partner. HIV diagnosis was made after a partner/child diagnosis in 40%; in 37% because women were symptomatic. Only 15% were diagnosed by screening, including during pregnancy (7.5%). 39% had sought medical care a median of 4 times because of symptoms related to HIV without being offered an HIV test. Median CD4 count at diagnosis was 154 (1Á1341). CD4 B200 at diagnosis was present in 58%, and B100 CD4 in 34%. Lower CD4 were found in women with lower education levels, women diagnosed with symptoms, and those who sought medical care before being diagnosed. 87% of women with previous pregnancies reported never being offered an HIV test.
Conclusions: Women living with HIV in this sample had low socioeconomic background, high prevalence of physical/sexual violence, and late stage disease at diagnosis. Missed opportunities for early testing (prenatal/primary care) were identified. In Mexico, HIV screening strategies are focused on selected groups that do not include women, unless they are pregnant. Women are diagnosed mostly when they become sick or after a family member is detected. Preventive policies should also address women; screening strategies need to be reinforced in primary care to increase early HIV detection in women. Chile, a 16.6 million-people upper middle-income country has a 0.3 )10 5 rate of HIV infection in adults, mostly cared by the Public Health System (PHS) through 34 AIDS care centers (ACC). Expanded access program (EAP) to HAART was begun in 2001 and there is now guaranteed free access to antiretrovirals and monitoring (CD4 count, viral load, and genotype) in the PHS (with low co-payment, also guaranteed for the privately insured). First-line HAART are assigned at the ACC but rescue therapies are approved centrally. Standards for professional staffing at ACC are based by norm on patient load. 32/ 34 ACC have enrolled their patient on HAART without exclusions in the Chilean AIDS Cohort ( !15,000 patients) for homogeneous management and evaluation of the EAP. In 5,000 treatment naïve patients, 45% initiated HAART in AIDS stage and 50% had baseline CD4 count B 100 cell/mL, (earlier treatment is more frequent lately). In this treatment, naïve population 5-year survival and AIDS-free survival were 90% and 70%, respectively. Three-year mortality decreased from 20.8% for those initiating HAART in 2001 to 3.4% in those doing it from 2008 onward. Cross-sectional study showed 73% of patients with undetectable viral load; median CD4 count increased from baseline of 164 to 358 cell/mL at last count. The expanded access to HAART guaranteed by law and the Chilean AIDS Cohort has been a successful synergistic initiative for the implementation of treatment and its evaluation in Chile. In persons with advanced HIV infection, the initiation of antiretroviral therapy occasionally provokes an inflammatory illness called immune response inflammatory syndrome (IRIS). In some instances, this is manifested as deterioration of an already recognized opportunistic illness (paradoxical IRIS) and in others, the inflammatory response allows recognition of an opportunistic illness that was sub-clinical before ART initiation (unmasking IRIS). In either setting, the occurrence of IRIS underscores the two edged nature of the immune response Á at the same time both responsible for defence against microbial pathogens and also responsible for the signs and symptoms of infection. While IRIS is clearly an inflammatory disorder, the precise mechanisms responsible for its appearance as viral replication are attenuated and systemic immunity restored remain incompletely defined.

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Update from the 20th CROI: Pathogenesis, Prevention and Treatment the pathogenesis, prevention, and treatment of HIV were presented and are reviewed here. In the realm of pathogenesis and HIV eradication, a study of patients with acute HIV infection showed that those treated with combination antiretroviral therapy (cART) during Fiebig Stage I had undetectable proviral DNA and negative viral outgrowth assays when tested after a year on therapy. Immediate treatment of an infant with evidence for maternal transmission of HIV led to apparent cure of the infant. A randomized study confirmed previous observations that intensification of cART with raltegravir leads to a transient increase in 2-LTR circles, strongly suggesting ongoing viral replication in at least some patients. Studies in HIV prevention included the disappointing results of the VOICE trial, which failed to show evidence of protection against HIV infection in women given oral or topical pre-exposure prophylaxis; poor adherence appears to explain this result. By contrast, studies in the macaque model demonstrated high rates of protection against vaginal SHIV challenge using a rilpivirine-containing vaginal ring, and against rectal challenge using a long-acting (monthly) injectable formulation of a novel integrase inhibitor. A study of the investigational integrase inhibitor dolutegravir in cART-experienced, integrase inhibitor-naïve patients showed that dolutegravir was superior to raltegravir when combined with ritonavir-boosted darunavir. The Second Line study of lopinavir/ritonavir (LPV/r) plus two nucleoside reverse transcriptase inhibitors (NRTI) versus LPV/r plus raltegravir as second-line cART showed the two regimens to be similar in overall efficacy. Lastly, the OPTIONS study showed that NRTI do not add significantly to the activity of salvage cART regimens that include more than two active agents from other classes. Introduction: Substance use is frequently encountered in HIV-infected individuals. The introduction of effective cART has led to a significant decrease in AIDS-related mortality and morbidity. However, these benefits may be less pronounced in drug users who may have reduced access to, or be less adherent with, cART. The objective of this study was to evaluate the frequency of self-reported substance use and its relationship to cART adherence using a questionnaire administered to outpatients attending an HIV clinic in Buenos Aires. Materials and methods: A rapid clinical screening tool was adapted from a previously validated questionnaire [1] and translated into Spanish for use in CCASAnet (Caribbean, Central and South America network for HIV epidemiology). The questionnaire was administered to all patients presenting for laboratory testing at Hospital Juan A. Fernandez, the CCASAnet site in Buenos Aires, between 15 Feb 2013 and 15 Mar 2013. Univariate comparisons of demographics and substance use were made between those patients on cART with and without missed doses. Chi-square tests were used for categorical variables. Results: The questionnaire was administered to 228 HIV-infected patients in care during a one-month period: 159 (69.7%) were male and median age was 41.4 years (IQR: 33Á48.8). Among 173 patients receiving cART, 33 (14.5%) reported missed ART doses in the previous seven days (median missed doses 2 [IQR: 2Á11]). Use of marijuana, cocaine, alcohol, and cigarettes within the previous seven days was self-reported by 11.4%, 6.6%, 36.8%, and 39.9% of patients, respectively. Compared to non-use, cocaine and alcohol use were associated with missed ART doses (cocaine use in those who missed/ did not miss doses: 18.2% vs. 2.8%, P:0.04; alcohol use 48.5% vs. 29.6% p:0.043). Marijuana use was not associated with missed doses. Conclusions: This pilot study confirms previous reports showing the linkage between substance abuse and lack of adherence. The point of care questionnaire was easily implemented and widely accepted and may be useful for identifying patients with increased risk for suboptimal adherence. Specific and culturally appropriate interventions are required to address this important barrier. Further analyses will assess the association of substance use and virologic suppression. This study was partially supported by CCASAnet/IeDEA, Grant awarded number UO1AI069923.  (1) Introduction: Several studies conclude that patients with HIV on antiretroviral treatment have higher risk of cardiovascular disease. The objective of this study was to assess cardiovascular risk in patients from Clinica Condesa, an HIV clinic in Mexico. Material and methods: This retrospective study included HIVinfected patients from Clinica Condesa with initial visit between 2009 and 2011 and had a complete lipid profile. The smoking status and systolic blood pressure were obtained from the patient's clinical file. General demographic information, total cholesterol, HDL cholesterol, and antiretroviral treatment were obtained from an integrated clinical and laboratorial database. The Framingham group assessment charts were used to evaluate cardiovascular risk, which was then categorized in high ( !20), medium (10 to 20) and low ( B10). Hypertriglyceridemia was defined as triglycerides !150 mg/dL, total hypercholesterolemia as !200 mg/dL, and low HDL cholesterol as B45 mg/dL. For statistical analysis, the 20.0 SPSS software was used. Results: Out of 399 patients included, 19 (5%) were women and 380 (95%) men. The total mean age was 37.7; 41.1 for women and 37.5 for men. Current smokers were 5 (1.25%) women and 200 (50%) men. The average systolic blood pressure was 110 SD98, HDL cholesterol 37.7 SD910.7, and total cholesterol 164 SD991. Only 4 (1%) men had high risk, 1 (0.3%) woman and 20 (5%) men were in medium, while 18 women (5%) and 354 men (89%) showed low risk. Comparisons of low group vs. medium and high group and found no differences in gender (95 vs. 96%), smokers (57 vs. 68%), low HDL cholesterol (79 vs. 88%), or antiretroviral therapy (85 vs. 60% on EFV/FTC/TDF). Differences were found in age, low-risk group had on average 36.7 while high and medium group had 54, prevalence of hypertriglyceridemia 55% (ICI 50% ICS 60%) vs. 96%(ICI 82% ICS 99%) and total hypercholesterolemia 12% (ICI 9% ICS15%) vs. 64% (ICI 44% vs. 81%). Conclusions: Although a low prevalence of high cardiovascular risk was found in Clinica Condesa, the prevalent metabolic alterations related to medium and high risk should be specially regarded. As the patients are predominantly young, growing older increases the risk factors for cardiovascular disease. There are conflicting data for this association. Studies in healthy volunteers demonstrate a transient effect of LPV/r on IR, whereas studies in HIV-infected individuals demonstrate minimal impact of LPV/r on insulin, glucose, or HOMA-IR levels after 48 weeks of antiretroviral therapy (ART). This retrospective analysis compared baseline (BL) and week 48 (WK48) insulin resistance parameters and triglyceride levels in subjects receiving LPV/r either as mono, dual, or triple ART. Materials and methods: Fasting glucose, insulin, HOMA-IR, and triglyceride (TG) levels were measured from plasma samples of 529 antiretroviral-naïve subjects in three randomized, prospective, multicentre studies (FRAN-03-001, M05-730, and M10-336). Of the 529 subjects, 486 subjects with BL and WK48 data were included: LPV/r monotherapy (n 0 70), LPV/r ' AZT/3TC (n 0 40), LPV/r ' FTC/TDF (n 0 280), LPV/r ' RAL (n 0 96). Within-group median changes from BL to WK48 were evaluated using the Wilcoxon signed-rank test. Results: Eighty percent of subjects were male, 77% were white, and 9% were Hispanic. At BL, 37% of subjects had CD4' T-cell counts B 200 cells/mL and 33% of subjects had plasma HIV-1 RNA ] 100,000 copies/mL. There was no significant increase in fasting glucose, insulin, or HOMA-IR levels from BL to WK48 for any treatment group. However, a significant increase in TG was observed from BL to WK48 in all treatment groups. Results were similar when 66 additional subjects receiving lipid-lowering or anti-glycaemic agents pre-or post-BL were excluded. Using regression analysis, LPV/r associated increases in TG did not appear to be associated with increased insulin resistance.
Conclusions: In this analysis, there was no evidence for the development of insulin resistance in HIV-infected subjects receiving LPV/r-based regimens. These findings challenge hypotheses associating LPV/r therapy and insulin resistance.   Introduction: Studies about the prevalence of diabetes mellitus in HIV-positive patients on HAART therapy show contradictory conclusions. This study aimed to find the prevalence of diabetes and whether specific antiretroviral treatment is associated with an increment amongst HIV patients on treatment.
Methods: A retrospective study was performed. HIV-positive patients on HAART whose first visit to Clínica Condesa was in 2009 to 2011 and are still active (last clinical visit within 2012) were included. General demographic information, antiretroviral therapy, CD4 and viral load were obtained from a clinical database; the general lab database provided fasting glucose levels. Diabetes mellitus was defined as doctor reported in the lab request and/or fasting glucose levels above 126 mg/dL. For analysis, SPSS 20 package was used. Results: In this study, 4,950 patients were included; the population was composed of 542 (11%) women, 4,288 (87%) men and 127 (3%) transgender men. The mean age was 39 years and average glucose was 90 mg/dL SD923. Diabetes was found in 2.5% (ICI 2% ICS 3%) of the patients; of this, 15% were women, 83% men, and 2% transgender men.
Conclusions: The prevalence of diabetes mellitus in Clínica Condesa was low relative to general Mexican population (7.34%). [1] There are several factors yet to be studied that may influence this prevalence, but this result is a hint that Mexican HIV population behaves differently.
Introduction: There is an increasing need to identify alternative antiretroviral (ARV) combinations for HIV ( Introduction: Options for antiretroviral therapy (ART) in patients receiving rifampin-containing anti-tuberculosis treatment (RIF anti-TB) are limited to EFV and more recently Raltegravir-containing regimens. In ART experienced subjects, few alternatives exist. The aim of this study was to describe a case series of co-infected patients who were treated with four nucleosides (4 NUCS) while on RIF anti-TB because of EFV resistance or intolerance.
Materials and methods: Retrospective, chart review study was conducted in two large HIV treatment centres in Mexico. We included all patients treated with a 4 NUCS combination comprised by Abacavir, Tenofovir, zidovudine and 3TC/FTC while receiving RIF anti-TB for active tuberculosis.
Results: From 1998 to 2012, 12 patients were included. Eleven (92%) were male. Median CD4' nadir cell count at baseline was 65 cell/ mm 3 (IQR 43-105). Only two (17%) patients were naive to ART. The median time of ART exposure before TB diagnosis was 23 (IQR 13.5Á23) months. Seven patients (58%) had used protease inhibitors before, and one patient (8.3%) used lopinavir ' ritonavir 800/ mg/d during RIF anti-TB before the 4 NUCS regimen. Three patients (25%) had history of liver disease at baseline. The reason for not using EFV was previous failure in nine (75%), and intolerance or contraindications for its use in the rest. Four of 10 treatment-experienced subjects had a genotype before the ARV change was made. Median time of 4 NUCS treatment was 6.5 (IQR 5Á17.5) months. Viral load B400 copies/ml was achieved in 58% of the patients. There was a median increase in CD4 cells of 81 cell/mm 3 (IQR 41-250) during the 4 NUCS treatment. One subject (8.3%) discontinued treatment because of intolerance. GIII-IV alkaline phosphatase elevation occurred in three (25%) subjects. Eight (67%) patients are alive and continue in follow-up.
Conclusions: Selection of ART remains a challenge for ART-experienced and EFV-intolerant patients who receive RIF anti-TB. In this case series a four nucleoside regimen, used mostly in patients with previous virological failure, was well tolerated and the majority of the patients achieved virological suppression.  Materials and methods: A total of 109 patients with undetectable viral load were divided into five groups: first suppressive therapy with efavirenz (26), first suppressive therapy with boosted protease inhibitors (PI) (25), salvage therapy using boosted PI (27), salvage therapy with raltegravir (15) and virological failure (16). Quantification of episomal and total DNA was performed by real-time PCR. Specific antibody quantification was performed using enzyme immunoassay capture. Results: Episomal DNA amplification was positive in 36 out of 109 patients' samples (33%) and quantification of total DNA was obtained in 94 patients' samples (86.3%). Individuals on salvage therapy using Raltegravir presented lower prevalence and lower quantitation of epissomal DNA as compared to other treatment groups (p 00.03).
There was no differences between groups in quantification of total DNA (p 00.298) or antibodies (p 00.126). The HIV-1 proviral load was higher among individuals with positive epissomal DNA (p 00.01).
There was a negative correlation between the episomal DNA quantification and (i) duration of treatment with undetectable viral load, (ii) CD4 counts, and (iii) CD8 counts. There was a higher prevalence of episomal DNA and a higher quantification of total DNA in virologic failure group (p 00.009 and 0.06, respectively). The antibody quantitation was higher among individuals on initial treatment using efavirenz compared to initial treatment with PIs (p 00.027).
Conclusions: Duration of treatment, CD4, CD8 counts, and raltegravir-based regimens relate to decreased residual viral replication (epissomal DNA). The relationship between episomal DNA and total DNA suggests replenishment of proviral reservoir with potential impact on HIV persistence. Lower antibodies levels among patients with PI-based initial treatment may suggest a more effective HIV suppression of these regimens, with higher capacity of decreasing the HIV antigenic component. Introduction: The determination of biological characteristics of the HIV strains is essential for the clinical handling in recently infected patients and to optimize your selection before starting treatment. The aim of this study was to relate the viral genotype and phenotype of the isolation from recently infected patient without treatment with the clinical-epidemiologic characteristics.
Methods: Peripheral blood mononuclear cells and plasma of Cuban patients HIV-1 recently infected, obtained at least eight months from the diagnostic date, were used for the isolation and capacity of syncytium-inducing (SI) and determination the subtype and resistance-associated mutations (RAMs) by sequence and analysis of the pol gene. The viral genotype and phenotype were related with the gender, sexual conduct, age, clinical status and count of CD4' cells of the patients at the moment of the diagnosis. Summary of results: We included in the study 38 treatment-naive HIV-1 infected patients, five women and 33 men. In male patients, 25 are men who have sex with men (MSM). The means values (range) of age and CD4' cells were 36.7 years (18Á68) and 386.8 cells/mm 3 (53Á 1260), prevailing the clinical status from A1 to A3 (31/38). We detected 13 subtypes B, 15 circulating recombinant forms (CRF) (9 CRF 20-23-24_BG, 6 CRF_19cpx and 2 CRF_18cpx), 3 unique recombinant forms (URF) (2 URF B/18cpx and 1 URF B/19cpx) and five non-amplified. Five viruses (13.2%) presented RAMs, one with multiresistance (subtype B) and other 4 for protease inhibitors (one subtype B and three recombinant forms). The virus was isolated from 63.2% (24/38) of the patients, who were related with the conditions MSM, 40Á50 years, clinical status A3 or superior, CD4' 5250 cells/mm 3 and infection with CRF; but not with the presence of RAMs. Only 25% of the strains were IS. Recombinant forms without RAMs were detected in all women, while in men there was no relation between sexual conduct and viral genotype. The presence of recombinant form was also associated with CD4' counts less than 500 cells/mm 3 .

Conclusions:
The results show that in Cuban patients HIV-1 recently infected treatment-naïve predominate non-SI strains and recombinant forms with RAMs. Introduction: Health and Human Services Guidelines state that treatment of older HIV-positive patients requires management of aging-related comorbidities in addition to HIV-infection, and that HIV itself may affect the biology of aging. This meta-analysis compared women aged B50 and]50 years receiving lopinavir/ritonavir (LPV/ r)-containing antiretroviral therapy (ART) to evaluate potential effects of age on safety, tolerability, and efficacy in women. Materials and methods: Meta-analysis included AbbVie or AbbViesupported AIDS Clinical Trials Group (ACTG) randomized clinical trials (RCTs) in adult subjects including women, LPV/r 800/200 mg/day as part of a 3-drug regimen, and follow-up duration]48 weeks. Virologic efficacy was evaluated using a random-effects meta-analysis; other endpoints were analyzed using pooled subject-level data.
Results: A total of 992 women from 11 RCTs (7 AbbVie, 4 ACTG) were included, with 889 women B50 and 103 women ]50 years old. 79.6% and 75.7% of women were ART-naïve in the B50 and]50 age groups, respectively. Baseline HIV-1 RNA level was similar between age groups. Baseline characteristics that differed by age group, and virologic and immunologic response by age group are summarized in the Table 1.
Overall discontinuation rates were similar; however, a smaller proportion of women B50 years discontinued due to adverse events (AEs)/HIV-related events (3.5% vs. 10.7%, p 00.002). Overall, 18.9% reported ]1 moderate-to-severe AE possibly related to study drug (16.6% vs. 37.9% in women B50 vs.]50 years, pB0.001). Significant differences (p B0.05) were observed between women B50 and ]50 years, respectively, in the proportion of subjects with postbaseline grade 3' laboratory abnormalities for amylase (1.6% vs. 6.8%), lipase (0.6% vs. 6.4%), creatinine clearance (2.0% vs. 12.1%), and cholesterol (3.2% vs. 14.9%). Conclusions: Women aged B50 and ]50 years had similar virologic and immunologic response, and overall discontinuation rates. Women ]50 had a higher incidence of moderate-to-severe treatment-related AEs and abnormalities in amylase, lipase, creatinine clearance, and cholesterol. These observations are consistent with baseline comorbidities and laboratory measures. Interactions between ART agents and other medications, differences in baseline laboratory values, additional comorbidities, and differences in baseline CD4 ' T-cells counts could contribute to these findings. Introduction: The number of HIV-infected adults over the age of 50 years is increasing. Recent studies of responses to HAART among elderly patients conducted in high-resource settings have demonstrated a CD4' cell reconstitution significantly slower despite a better virological response in this age group. We compared the virological and immunological response to first-line HAART in subjects !50 years old compared to younger patients in Mexico. Methods: Retrospective cohort study of patients with HIV infection receiving medical care at INCMNSZ in Mexico City. All treatmentnaive patients who started HAART between 2007 and 2012 were evaluated for CD4 recovery and virologic response. Immunological response (IR) (increase of CD4 cell count !100/mm 3 and virological response (HIV RNA B400 copies/ml) at one year were compared in subjects initiating treatment at !50 years of age with those initiating at a younger age. Patients lost to follow-up (LTFU) and incomplete data were included in an intention to treat analysis (ITT). Results: Eight-hundred thirty-six patients started HAART between 2007 and 2012; 742 (89%) with B50 years and 94 (11%) !50 years of age. Only 723 (86%) patients completed at least 12 months followup. Demographic and clinical baseline characteristics are presented in Table 1. By 12 months after starting HAART, 75% of patients B50 years of age experienced IR, compared with 63% in ]50 years (p 00.09); the median gain in the CD4' cell count was 173 cell/mm 3 in B50 years and 144 cell/mm 3 in ]50 years of age (p 00.08). VR was similar in both age groups, 97% in B50 years and 98% in ]50 years of age (p0 0.71) ( Table 2).In the ITT analysis, 46% of patients B50 years achieved IR, whereas in the group ]50 years only 35% (p 00.05) ( Table 3). Conclusions: Among HIV-infected elderly population, the immunological response after 12 months of HAART was lower in the group of patients who started HAART at or after 50 years of age, with a trend toward statistical significance. We found no significant difference in virologic response between the two groups. Introduction: The Specialized Condesa Clinic of Mexico City is a detection, treatment and follow up centre for people with HIV/AIDS and sexually transmitted infections (STI), with a care program of HIV and STI for victims of sexual violence since 2008. According to research, almost one in four women can be a victim of sexual violence and one in three female adolescents informs that her first sexual experience was forced. Sexual violence is associated with sexual health problems later on and thus, considered a public health problem. Materials and methods: Cross-sectional study of data from female patients who attended the sexual violence program. The data collection tool used was a seroepidemiologic questionnaire which collected the clinical history along with blood tests from January 2, 2012 through December 31, 2012. The study sample was of 1,071 female patients, all received antibody HIV 1-2, surface antigen HBV, antibodies for HCV and Syphilis antibodies testing. All tests were performed during the initial visit and during each follow up visit at three and six months. All patients who procured services within 72 hours from the event received post exposure prophylaxis treatment for HIV, Gonorrhea, Syphilis, Trychomoniasis, Chlamydia and emergency contraception. Results: Of the 1,071 patients 44 were under 12 years (4.1% of total); 150 were 12Á14 year olds and 354 were 15Á19 year olds; for a total of 504 adolescent patients (47% of total). The average age of patients was 22.2 years (range of 8 to 82). Four-hundred and one patients (37.4%) accessed the service within 72 hours after the sexual violence event, while 670 patients (62.5%) accessed services afterwards. Five-hundred and thirty six patients received emergency contraception. Four-hundred one patients received HIV PEP for 28 days. They also received prophylaxis for STI. During initial screening two patients (0.18%) had a positive HIV result, and two (0.18%) had a positive HCV result. These infections were not acquired during the sexual violence event. Nine patients had pregnancies related to the sexual violence event, six terminated their pregnancies legally, two refused interruption and one was too late to perform the interruption. During the follow-up visits, no patients showed with HIV or STI infection. Conclusions: Medical care to victims of sexual violence is a priority since it prevents HIV, STI and unwanted pregnancies. The time after the sexual violence event is crucial since if care is not rendered in time it could result in negative lasting consequences. L10I substitution was associated significantly with subtype B, 19 CPX and BG. The proportion of substitution K20I/R in the FRC 18 cpx and BG was considerably higher than others. In the latter was detected more frequently the combination of the two substitutions. A low level of resistance to nelfinavir was found in 83% of samples, related to the presence of changes at positions 10 and 20 of the PR. Conclusions: Significant differences in the prevalence of resistance to PI were not detected among the most frequent genetic forms from naive-treated patients, but differences between some amino acids changes should be taken into account. The presence of transmitted resistance mutations supports the study of resistance at the baseline of treatment. Introduction: The pre-existence of antiretroviral (ARV) drug resistant virus is strongly associated with treatment failure in naive treatment patients, for that the knowledge of transmitted drug resistance (TDR) in newly diagnosed patients constitutes a fundamental premise in the epidemiological surveillance. The aim of this study was to analyze the profile of TDR in newly diagnosed patients from Havana city. Methods: One hundred and twenty-seven HIV-1 infected patients from Havana and diagnosed between 2009 and 2012 were included in the study. The viral RNA was isolated from plasma and used as target to amplify the pol gene by RT-nested PCR. PCR products were sequenced and the data generated used to determine the viral subtype by phylogenetic analysis. The TDR were detected by HIVdb v6. Introduction: Since 2001, Cuba achieved universal antiretroviral therapy with domestically manufactured antiretroviral (ARV) for patients meeting international clinical criteria and has resulted in a decrease in AIDS mortality rate and incidence of opportunistic infections. However, the emergency of HIV-1 drug resistance is strongly associated with treatment failure. The aim of this study was to analyze the associated mutations to ARV resistance and the resistance levels in a group of patients that attended to the infectious diseases outpatients department of Hermanos Ameijeiras Hospital, Havana City with treatment failure during the year 2012. Methods: During 2012, were collected 25 plasma samples from HIV-1 patients with treatment failure of 157 HIV patients that attended to the infectious diseases outpatients department of Hermanos Ameijeiras Hospital. The viral RNA was used as target to amplified and sequenced pol gene. The viral subtype and the drug resistance mutations and levels were determined. The time between the appearance of resistance and the beginning the last therapy was considered.
Results: Most of the patients were MSM (96%) and 52% had only received first-line HAART. Subtype B was the most prevalent subtype (52%) followed by non-B subtypes (CRF19_cpx, CRF 20-23-24_BG, URF and CRF18_cpx). Drug-resistant mutations were detected in 21 patients (84%). Of them, 61.9% presented mutations against both NRTI and NNRTI, 19.1% to the combination PI ' NRTI, 9.5% to NRTI, and 9.5% to NNRTI. The most frequent mutation for NRTI was M184V (56%), while for NNRTI were Y181C/I/V (24%) and K103N (20%). As high as 64% presented high resistance to all or some of the drugs used as first-line HAART in Cuba (AZT/D4T ' 3TC ' NVP). The average of years in the appearance of resistance after beginning the last therapy was of 2.3 years. The therapeutic failure of 16% of the patients that presented susceptible virus was due to the poor adherence to HAART.
Conclusions: This study evidenced the high resistance levels to the first-line regimens prescribed in Cuba, as well as the fast appearance of resistant variants after beginning the therapy. These results emphasize the necessity of the monitoring of the resistance in those patients that will begin a new therapeutic regimen.