Decreased mother-to-child transmission
The use of antiretroviral drugs has blocked mother-to-child transmission (MTCT) effectively enough to have almost eradicated this form of transmission in the developed world. With no treatment, transmission rates in Europe and the United States were 15–30% and this was reduced to approximately 1–2% with the advent of HAART . In the developing world, where antiretroviral drugs are not widely available, MTCT remains a major cause of HIV transmission. There was an inexcusable delay in getting these drugs into developing areas of the world, but when eventually trialed in these populations it was shown that short-course antiretroviral drugs (zidovudine and lamivudine) in late pregnancy and during and after birth, or single-dose nevirapine given to mothers in labor and their baby immediately after birth, could significantly reduce MTCT rates. This effect was seen even in breastfeeding populations, essential in areas where clean drinking water is unavailable and breast feeding must be encouraged .
International response to the HIV/AIDS pandemic
Since the United Nations Declaration of Commitment on HIV/AIDS in 2001, pledges and commitments for total annual resources available for HIV care rose from US$1.6 billion to US$8.2 billion in 2005, and the number of people receiving antiretroviral drugs increased fivefold worldwide and up to eightfold in southern Africa . Despite this apparent commitment, the pandemic is outpacing the global response; in 2005 there were more AIDS deaths and new HIV infections worldwide than ever before . Under the original ‘3 by 5’ goal set by the WHO and UNAIDS in 2001, three million people were meant to be on the antiretroviral drug treatment they needed by 2005; that target was not met, and only 1.3 million people were receiving treatment by the end of 2005, with an estimated 2 million receiving antiretroviral drugs by 2006. Only approximately one in five people in low and middle-income countries receive the antiretroviral drugs they need. Approximately one in six of the 4.7 million people in need of antiretroviral drugs in sub-Saharan Africa were receiving them in 2005; however, access is uneven between countries, with coverage reaching or exceeding 50% only in Botswana, Namibia and Uganda . In some areas only 11% of HIV-positive pregnant women received antiretroviral drug treatment that would help prevent MTCT, and only 15% of children in need of treatment had access to it . Despite measurable successes in some countries, universal access remains a distant prospect in other countries.
Issues around antiretroviral drug roll-out in low-income countries
Mortality rates in HIV-infected patients from low-income settings in Africa, south America and Asia have been shown to fall substantially within the first few months of HAART, approaching those seen in western Europe and north America after approximately 4–6 months of treatment, and the provision of free treatment in low-income settings is associated with lower mortality . Patients in low-income countries in this study had increased mortality rates in the first few months of therapy compared with those from developed countries . This difference could be explained partly by the fact that patients from low-income countries tended to have lower CD4 cell counts and more advanced disease at diagnosis than those from high-income countries. Many HIV/AIDS patients in resource-poor countries also have other underlying co-morbidities, such as tuberculosis and invasive bacterial and fungal infections, which, given the limited access to therapies for such infections in low-income countries, may also contribute to this initial high mortality.
Despite concerns, evidence suggests that favorable levels of adherence can be achieved in sub-Saharan African settings, at least in the initial stages when the patient is experiencing major improvements in their health and wellbeing . Adherence is essential for successful viral suppression and to reduce the risk of viral resistance. Adherence with full viral suppression is an important predictor of survival, and treatment interruptions are an important predictor of drug resistance . Failure to suppress virus replication completely has been shown to result in the development of resistance to some antiretroviral drugs, especially protease inhibitors, even at relatively high levels of adherence [16,17]. In industrialized countries, regular measurement of the viral load is routinely used to monitor therapy and to evaluate adherence. Unless monitoring of viral load is adopted alongside the introduction of antiretroviral drugs in developing countries, the risks of drug resistance arising and being transmitted are greatly increased; unfortunately, the necessary laboratory infrastructure for such monitoring is not currently available in most countries of sub-Saharan Africa .
Slowing the pandemic
Overall, improved access to treatment seems to be having some effect in reducing HIV transmission. Effectively slowing the pace of the HIV/AIDS pandemic is, however, a complex issue; we can keep people alive longer and hope that we can make them less infectious through treatment, but treatment alone cannot stop transmission and other strategies are needed. One recently recommended measure is male circumcision. Recent trials in Uganda , Kenya  and South Africa  demonstrated 55–60% reductions in the risk of HIV acquisition in men who had been circumcised, highly statistically significant findings. In response to these findings, the WHO and the UNAIDS Secretariat convened an international expert consultation to determine whether male circumcision should be recommended for the prevention of HIV infection. Experts attending the consultation recommended that male circumcision should be recognized as an additional important intervention to reduce the risk of heterosexually-acquired HIV infection in men as part of a comprehensive HIV prevention package throughout the world.
HIV/AIDS: the shift from a fatal to a chronic disease
Although decreasing the mortality associated with HIV/AIDS may seem a distant prospect in many areas of the world, real progress is being made in others. Between 1987 and 1994, for example, HIV/AIDS was a major cause of death in the United States, with the death rate increasing every year to become the leading cause of death in young adults. With the advent of antiretroviral drugs, and especially the introduction of protease inhibitors in the mid-1990s, mortality began to decrease significantly (Fig. 4) . This trend is evident in other developed countries and, as already discussed, we are also beginning to see similar trends in some of the resource-poor countries who are best managing the epidemic. The decreases in AIDS-related mortality are an encouraging sign that HIV-infected individuals are living better and longer lives, although it is important to bear in mind that the improvement in clinical management and patient survival must be matched by reductions in the incidence of new HIV infections if the pandemic is to be contained.
As management improves, people with HIV/AIDS will be living longer and, therefore, will become increasingly susceptible to the chronic diseases we are now beginning to recognize as long-term sequelae of this disease. A recent US HIV outpatient study has shown that, although the death rate from AIDS-related causes fell significantly between 1996 and 2004, the proportion of deaths from non-AIDS-related diseases increased . This increase was especially prominent in non-AIDS malignancies, hepatic disease and cardiovascular and pulmonary disease. As mortality from HIV/AIDS continues to improve, these long-term consequences of infection will become of increasing significance and will require comprehensive management strategies.
In conclusion, the HIV/AIDS pandemic continues unabated throughout the world, with successes in some areas being outweighed by the acceleration of spread in others, including eastern Europe. Only a more universal, targeted approach, incorporating both prevention and treatment, will succeed in limiting that spread. We will need innovative methods for early diagnosis coupled with counselling in order to initiate treatment strategies as early as possible. We will also need to emphasize novel methods of prevention, including male circumcision, microbicides and pre-exposure prophylaxis, if we are to have any effect on limiting the spread of this disease. Although a vaccine is not likely to be available in the near future, there have been promising breakthroughs in research on vaccines that reduce viral load, decreasing chances of transmission. As a preventive HIV vaccine is probably still at least a decade away, we are going to rely on treatment as well as prevention modalities to try to slow this pandemic and to manage the effects of a disease which still, despite our efforts, leaves millions dead throughout the world every year.
We now have treatment options, which, at least in those patients who have access to them, are essentially converting a disease that was historically fatal in a relatively short time period into a chronic living disease. The consequences of this paradigm shift in outcome is that people living with HIV are now at greater risk of developing previously unrecognized long-term complications, some of which are discussed in detail in this supplement.
Conflicts of interest: None.
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Keywords:© 2008 Lippincott Williams & Wilkins, Inc.
AIDS; epidemiology; HIV; mortality