HIV treatment cascades
2015; Lippincott Williams & Wilkins; Volume: 29; Issue: 18 Linguagem: Inglês
10.1097/qad.0000000000000864
ISSN1473-5571
Autores Tópico(s)HIV/AIDS drug development and treatment
ResumoIn 2014, UNAIDS set the '90–90–90' target – aiming to diagnose 90% of all HIV-positive people, provide antiretroviral therapy for 90% of those diagnosed and achieve undetectable HIV RNA for 90% of those treated, by the year 2020 [1]. According to epidemiological predictions, this strategy could lower the number of new HIV infections and deaths by 70–80% by 2030 [2]. There are currently 37 million people infected with HIV worldwide, and 15 million taking antiretrovirals. If there were no new HIV infections in the next 5 years, meeting the UNAIDS targets would involve 33 million people being diagnosed, 30 million taking antiretrovirals and 27 million with HIV RNA suppression. However, meeting the UNAIDS targets by 2020 would also need to include testing and treating all those newly infected in the next 5 years. There were two million new infections in 2014 alone, so it is likely that at least 35 million people would need to be on treatment by 2020 to include newly infected people in the 90-90-90 targets. The report by Kohler et al.[3] in this issue of AIDS shows the current HIV treatment cascade for Switzerland. This country is the closest to reaching the UNAIDS targets. Of the 15 200 people estimated to be HIV positive in Switzerland, 12 300 (81%), were diagnosed HIV-positive, 10 800 (71%) were taking antiretrovirals and 10 400 (68%) had HIV RNA suppression less than 200 copies/ml. The overall outcome of the Swiss treatment cascade is just under the UNAIDS target of 73% of all HIV-positive people with HIV RNA suppression. If a country with the wealth and organization of Switzerland is close to reaching these targets, is there the potential for other countries with fewer resources or less integrated health systems to succeed? Interpreting country level cascades, and comparing between countries, requires more standardization of how they are measured [4]. In the Swiss treatment cascade [3], there is uncertainty about the true size of the national HIV epidemic, which could affect estimates of the number of undiagnosed people; this uncertainty is seen in epidemiological estimates for all countries. Different measures of viral suppression (e.g. <50, <200 or <1000 HIV RNA copies/ml) affect the estimate of percentage with viral suppression. There is continuing discussion over standards for reporting country-level cascades should be reported [5]. In addition, country-level cascades need to be updated regularly, as treatment levels improve over time. Table 1 shows the estimated percentage of HIV-positive people taking antiretrovirals in 20 countries, based on the UNAIDS 2014 database for lower or middle income countries with at least 40 000 HIV-positive people [6]. The table shows the 10 countries with the highest percentage of HIV-positive people on treatment, and the 10 lowest. Treatment coverage in Botswana is at 70%, very close to the current level in Switzerland (71%). There are other countries (e.g. Rwanda, Cambodia) with very impressive treatment coverage rates. However at the other end of the scale there are countries in Africa, Asia and the Middle East with less than 10% of HIV-positive people on antiretroviral treatment. Coverage rates range widely between countries in the same regions. Rwanda, with 61% coverage, borders on the Democratic Republic of Congo, where coverage is 18%. Cambodia, with 68% coverage, is close to Indonesia, with 9% coverage.Table 1: Countries with highest and lowest antiretroviral treatment coverage rates (UNAIDS 2014 database).A recent overview of HIV treatment cascades by country has also showed wide diversity between countries. In this analysis of 11 countries with national-level cascades, the percentage of HIV-positive people on antiretroviral treatment was high in Western Europe (e.g. 68% in the UK and 64% in the Netherlands), but particularly low in Eastern Europe: 26% in Georgia, 22% in Ukraine, 19% in Kyrgyzstan and 11% in Russia [7]. The results from these two surveys show that several high, middle and low-income countries are already approaching the UNAIDS 90–90–90 target. However there are other countries still far from optimal coverage levels, which need increased political will and/or funding to improve over the next 5 years. We cannot assume that all countries which reach the UNAIDS 90–90–90 target will have parallel reductions in new HIV infections. In Australia and the UK, although antiretroviral treatment coverage has improved in the last 5 years, there has been no reduction in the number of new HIV infections [8,9][8,9]. A small percentage of undiagnosed HIV-positive people could potentially drive an epidemic, if there is substantial behavioural disinhibition, and if policies of harm reduction are not successfully implemented alongside increased testing and treatment. Only three countries – USA, Thailand and Malaysia – are currently implementing preexposure prophylaxis, despite clear benefits in lowering HIV transmission rates in two randomized trials [10]. Increasing the number of people on antiretroviral treatment from 15 million to 30–35 million requires careful choices of drugs. The current WHO standard first-line treatment is tenofovir (300 mg/day) in addition to lamivudine (300 mg/day) and efavirenz (600 mg/day), which has a minimum cost of $122 per person per year in low-income countries [11]. This combination requires 1200 mg of active pharmaceutical ingredient per person per day. A proposed alternative is tenofovir alafenamide (25 mg/day) including emtricitabine (200 mg/day) and dolutegravir (50 mg/day), which is predicted to cost only $60 per person per year [11]. This combination requires 275 mg of active pharmaceutical ingredient per person per day, 73% less than the current efavirenz-based combination. When millions of people are being treated, small reductions in the unit cost of treatment could generate significant savings, which could free resources to treat more people. For example, treating 30 million people in low-income countries would cost $3.66 billion per year using tenofovir/lamivudine/efavirenz ($122 per person), versus $1.8 billion per year using tenofovir alafenamide/emtricitabine/dolutegravir ($60 per person). Potential savings of this size suggest that new randomized trials of lower-cost antiretroviral combinations should be prioritized. In middle and high-income countries, most antiretrovirals will become generic by 2018, but patents on newer treatments or co-formulations remain enforced. To reach the UNAIDS 90–90–90 targets in these countries, there will need to be difficult decisions made between using older but cheaper generic drugs, versus the most modern but far more expensive new single pill combinations. For example, in the USA, abacavir/lamivudine/dolutegravir has been priced at $28 000 per person per year, which is 230 times higher than the target price for the generic tenofovir/lamivudine/efavirenz shown above. Parts of the data have been presented at the CROI Conference February 23–26, 2015 in Seattle. Acknowledgements Conflicts of interest There are no conflicts of interest.
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