Ying-Ru Lo

Highly active antiretroviral treatment as prevention of HIV transmission: review of scientific evidence and update.

Purpose of reviewAn estimated 33 million people are living with HIV and universal access remains a dream for millions of people. By the end of year 2008, four million people were on treatment; however, over five million needed treatment, and in 2007, there were 2.7 million new infections. Without significant improvement in prevention, we are unlikely to meet universal access targets including the growing demand for highly active antiretroviral treatment (HAART). This review examines HAART as a potential tool for preventing HIV transmission. Recent findingsWe discuss recent scientific evidence regarding the treatment and prevention gap, importance viral load and HIV transmission, HAART and HIV transmission, when to start, HIV counseling and testing, modeling results and next steps. SummaryHAART has considerable treatment and prevention benefits and it needs to be considered as a key element of combination prevention. To explore HAART as an effective prevention strategy, we recommend further evaluation of human rights and ethical considerations, clarification of research priorities and exploration of feasibility and acceptability issues.

Highly active antiretroviral treatment for the prevention of HIV transmission.

In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV.Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates

Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts

13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment.HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing ones HIV status is key for prevention efforts, it is not known with certainty when to start HAART.Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability issues.

Can antiretroviral therapy eliminate HIV transmission

There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies.

Preventing HIV transmission with antiretrovirals

www.thelancet.com Vol 373 January 3, 2009 7 successful campaign to reduce alcohol consumption and stem the rising incidence of variceal bleeding as well as the other tragic consequences of alcoholic liver disease is essential. Organisationally, the patchwork service in which patients can still be admitted to hospitals without out-of-hours endoscopy needs to be replaced with one that ensures that all necessary diagnostic and treatment facilities are available.

Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities

Three of the most extraordinary events in global health over the past 30 years have been the emergence of the pan-demic of HIV/AIDS, the development of antiretroviral therapy (ART) capable of arresting HIV progression and reduc-ing mortality, and scale-up of therapy in low- and middle-income countries. By the end of 2007, approximately 3 million people were accessing ART in resource-constrained settings,

Effects of HIV Antiretroviral Therapy on Sexual and Injecting Risk-Taking Behavior: A Systematic Review and Meta-analysis

There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting.

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers

BACKGROUND Increased global access and use of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) has been postulated to undermine HIV prevention efforts by changing individual risk-taking behavior. This review aims to determine whether ART use is associated with changes in sexual or injecting risk-taking behavior or diagnosis of sexually transmitted infections (STIs). METHODS A systematic review and meta-analysis was conducted of HIV-seropositive participants receiving ART compared with no ART use in experimental or observational studies. Primary outcomes included (1) any unprotected sexual intercourse, (2) STI diagnoses, and (3) any unsafe injecting behavior. RESULTS Fifty-eight studies met the selection criteria. Fifty-six studies containing 32 857 participants reported unprotected sex; 11 studies containing 16 138 participants reported STI diagnoses; and 4 studies containing 1600 participants reported unsafe injecting behavior. All included studies were observational. Unprotected sex was lower in participants receiving ART than in those not receiving ART (odds ratio [OR], 0.73; 95% confidence interval [CI], .64-.83; P < .001; heterogeneity I(2) = 79%) in both high-income (n = 38) and low-/middle-income country (n = 18) settings, without any evidence of publication bias. STI diagnoses were also lower among individuals on ART (OR, 0.58; 95% CI, .33-1.01; P = .053; I(2) = 92%); however, there was no difference in injecting risk-taking behavior with antiretroviral use (OR, 0.90; 95% CI, .60-1.35; P = .6; I(2) = 0%). CONCLUSIONS Despite concerns that use of ART might increase sexual or injecting risk-taking, available research suggests that unprotected sex is reduced among HIV-infected individuals on treatment. The reasons for this are not yet clear, although self-selection and mutually reinforcing effects of HIV treatment and prevention messages among people on ART are likely.

Harnessing the prevention benefits of antiretroviral therapy to address HIV and tuberculosis

HIV epidemics in the Asia‐Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre‐exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia‐Pacific region, including opportunities and barriers.

A prospective “test-and-treat” demonstration project among people who inject drugs in Vietnam

After 30 years we are still struggling to address a devastating HIV pandemic in which over 25 million people have died. In 2010, an estimated 34 million people were living with HIV, around 70% of whom live in sub-Saharan Africa. Furthermore, in 2009 there were an estimated 1.2 million new HIV-associated TB cases, and tuberculosis (TB) accounted for 24% of HIV-related deaths. By the end of 2010, 6.6 million people were taking antiretroviral therapy (ART), around 42% of those in need as defined by the 2010 World Health Organization (WHO) guidelines. Despite this achievement, around 9 million people were eligible and still in need of treatment, and new infections (approximately 2.6 million in 2010 alone) continue to add to the future caseload. This combined with the international fiscal crisis has led to a growing concern regarding weakening of the international commitment to universal access and delivery of the Millennium Development Goals by 2015. The recently launched UNAIDS/WHO Treatment 2.0 platform calls for accelerated simplification of ART, in line with a public health approach, to achieve and sustain universal access to ART, including maximizing the HIV and TB preventive benefit of ART by treating people earlier, in line with WHO 2010 normative guidance. The potential individual and public health prevention benefits of using treatment in the prevention of HIV and TB enhance the value of the universal access pledge from a life-saving initiative, to a strategic investment aimed at ending the HIV epidemic. This review analyzes the gaps and summarizes the evidence regarding ART in the prevention of HIV and TB.