Could highly active antiretroviral therapy reduce HIV transmission? (update)
Combined antiretroviral therapy has been shown to reduce viral load in HIV. However, is it possible that the use of such therapy could also ultimately reduce HIV transmission? Dr Gordon Scott reviews the evidence, including a promising study from Taiwan which has suggested this could be the case.
- Sexual transmission of HIV infection is well understood, but changing sexual behaviour to prevent spread of infection is proving difficult.
- Vaccines to prevent HIV infection are not likely to become available in the near future.
- Low levels of HIV in the blood are associated with reduced risk of transmitting infection, and drug treatment usually reduces blood HIV to undetectable levels.
- A report from Taiwan, a low prevalence area for HIV infections, shows that treatment of infected individuals can reduce HIV transmission.
- Similar results may not be possible in high prevalence countries with less extensive HIV testing and significant importation of HIV-infected individuals from abroad.
Declaration of interests: Dr Scott has received financial support from Pharmaceutical companies to attend international conferences on HIV. He has also received consultancy fees from Bristol-Myers Squib (lapsed) and Gilead Pharmaceuticals (current).
Despite there being a clear understanding of the mechanisms by which human immunodeficiency virus (HIV) is transmitted, prevalence continues to rise in many countries. Change in sexual behaviour has been difficult to maintain and vaccination seems as far away as ever; so are there any medical interventions that could play a role in limiting the spread of HIV?
At an individual level, low levels of HIV in the blood (viral load) have been shown to be associated with reduced risk of sexual transmission compared with individuals who have high viral load.1 Many drugs that inhibit various aspects of HIV replication are now available. This has allowed the prescription of effective combinations, often referred to as highly active antiretroviral therapy (HAART), which in most cases reduces viral load to undetectable levels in blood and leads to significant reduction in ill-health (acquired immune deficiency syndrome) and death. However, in addition to improving clinical outcome, HAART might also be anticipated to reduce an individual’s risk of transmitting HIV to others. For obvious ethical reasons, this theory is impossible to test in a controlled scientific fashion, but mathematical models do support the concept.2 Furthermore, observational studies in the setting of mother-to-child-transmission of HIV show a strong association between reducing viral load and reduced rates of neonatal infection.3
Could making HAART freely available reduce HIV transmission at a population level in the absence of change in sexual behaviour? To do so, all, or nearly all, prevalent cases would have to be diagnosed, including imported cases. Then, all positives for HIV would have to be treated with effective regimes to which they adhered. Good adherence is critical in preventing both treatment failure and the emergence of drug-resistant strains of HIV that may be transmitted to others.4
A recent paper would suggest that Taiwan has successfully addressed these issues, but there are aspects of the adopted approach that may make this outcome difficult to achieve in other countries such as the UK.5 In reference to HIV testing in Taiwan, the authors state that high-risk sexually active populations were ‘encouraged or persuaded to receive voluntary testing’. This implies a degree of coercion unlikely to be acceptable in this country. Mandatory military service for all men at 20 years of age, with compulsory testing at enlistment, affords an opportunity to screen systematically in a way not available to most countries. No mention of imported HIV is made in the paper, which presumably reflects its low potential impact upon HIV prevalence. However, many countries, such as the UK, have relatively high levels of imported, as opposed to indigenous, infection.
ACCESS TO TREATMENT
After the advent of HAART in the mid-1990s, an aggressive treatment approach, referred to in the paper as ‘early intensive treatment’, quickly became favoured in the USA and other countries. However, European reluctance to go down this path gathered momentum as the difficulties of adhering to complex regimes with unpleasant side-effects became apparent. Maintenance of such an approach is likely to have resulted in many individuals developing long term drug side-effects such as high blood cholesterol levels in association with body fat redistribution (lipodystrophy).6
The authors highlight that rates of syphilis and gonorrhoea are comparable before and after the introduction of HAART, implying that change in sexual behaviour is unlikely to account for reduced HIV transmission. This is probably fair, although the link between syphilis and HIV transmission is not necessarily as simple as implied in the paper. Most outbreaks of syphilis among gay men in the UK have been associated with transmission by oral sex, a less risky practice for HIV transmission.7
Taiwan is a country with low prevalence of HIV infection, low numbers of imported cases, systematic HIV testing of a significant proportion of the population, and early initiation of antiretroviral therapy. In this situation, free availability of HAART probably has contributed to reduced HIV incidence. Many countries, including the UK, have also made HAART freely available, but in the absence of control of the other factors outlined above we can anticipate, unfortunately, a continuing rise in the number of HIV-infected people.
- Gray RH, Wawer MJ, Brookmeyer R et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001; 357(9263):1149–53.
- Gray RH, Li X, Wawer MJ et al. Stochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, Uganda. AIDS 2003; 17(13):1941–51.
- Leroy V, Montcho C, Manigart O et al. Maternal plasma viral load, zidovudine and mother-to-child transmission of HIV-1 in Africa: DITRAME ANRS 049a trial. AIDS 2001; 15(4):517–22.
- Pillay D. Current patterns in the epidemiology of primary HIV drug resistance in North America and Europe. Antivir Ther 2004; 9(5):695–702.
- Fang CT, Hsu HM, Twu SJ et al. Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. J Infect Dis 2004; 190(5):879–885.
- Tershakovec AM, Frank I, Rader D. HIV-related lipodystrophy and related factors. Atherosclerosis 2004; 174(1):1–10.
- Cook PA, Clark P, Bellis MA et al. Re-emerging syphilis in the UK: a behavioural analysis of infected individuals. Commun Dis Public Health 2001; *4:*253–8.