During the past decade, the collective efforts of activists, researchers, service providers, pharmaceutical companies, policymakers, and international agencies have generated real momentum in scaling up HIV treatment and prevention across the globe, with special emphasis on Africa. The successes have been immense, but so too the challenges.

In July 2000, diverse groups from around the world joined forces at the 13th International AIDS Conference in Durban, South Africa, to demand global access to HIV treatment. Shortly thereafter, the Global Fund to Fight AIDS, Tuberculosis and Malaria was conceived, followed by the U.S. President's Emergency Plan for AIDS Relief. Since then, the number of people receiving antiretroviral therapy (ART) in low- and middle-income countries has increased dramatically, from 300,000 in 2002 to approximately 6.65 million by December 2010.1 South Africa, the country with the largest number of people living with HIV, has the largest ART program in the world, with approximately 1.8 million people estimated to have received ART by April 2011.2 Progress is also being made around children's access to ART, with an estimated 456,000 receiving treatment by the end of 2010.1

Escalating ART coverage in some parts of Africa is starting to have an effect at the community level, with evidence of declines in morbidity and mortality. According to the WHO, overall life expectancy has been increasing in countries where ART is being implemented. For example, from 2000 to 2009, life expectancy at birth increased from 51 to 55 years in Tanzania, from 47 to 52 years in Uganda, and from 47 to 59 years in Rwanda.3 Emerging evidence also suggests that increasing ART coverage leads to reductions in HIV incidence. A prospective, observational study conducted from 2004 through 2011 in a rural district of South Africa showed that for every percentage increase in the proportion of HIV-infected adults receiving ART, there was a corresponding 1.7% decrease in the risk for HIV acquisition among uninfected adults. When ART coverage was >30%, the risk for HIV acquisition was reduced by approximately 38%.4

Despite major advances in the rollout of ART across resource-constrained settings, significant challenges remain around scaling up ART to individuals who need it and sustaining those already on treatment.

Unmet Need for ART Estimating the exact number of people who are eligible for HIV treatment but not yet receiving it is made complicated by changing guidelines. However, if one considers a CD4 count <350 cells/mm3 as the threshold for ART initiation, as recommended by the WHO,5 then only about 52% of all eligible patients in South Africa were receiving treatment by the middle of 2011.2 Estimated ART coverage in other low- and middle-income countries ranges from 26% in Nigeria to 93% in Botswana.1 Clearly, more needs to be done to increase access to treatment.

Low Uptake of HIV Testing One of the main challenges to getting more people on treatment is that many people remain unaware of their serostatus. Although HIV testing has increased substantially in sub-Saharan Africa and some other areas of the continent, the proportion of people most at risk who do not know whether they are HIV-infected is astounding: 75% in South Africa, according to a 2008 national HIV survey (the most recent one conducted there),6 and 83% in Kenya, according to a 2007 national survey.7

Ensuring that people are aware of their level of risk and that they seek regular testing for HIV is a global challenge, but one that is particularly difficult in Africa, where stigma remains rife.8 The people who are at the highest risk for HIV infection are not only likely to deny their risk but also to experience discrimination and social marginalization on a daily basis, which further contributes to their reluctance to be tested.

Some novel approaches have been implemented to scale up HIV counseling and testing (HCT) in Africa. For example, South Africa launched an aggressive national HCT campaign in April 2010 to encourage 15 million sexually active individuals to test for HIV over a 12-month period. An important feature of this campaign was that it was a partnership between government, private sector, and nongovernmental organizations. By June 2011, an astounding 14.8 million counseling sessions and 13 million HIV tests had been conducted, as well as 8 million tuberculosis tests.9 While this is a laudable achievement, there is limited evidence available on the extent to which people who were found to be HIV-infected were effectively linked to prevention and care services. The struggling public healthcare systems in many resource-constrained countries discourage many patients from trying to obtain medical help. One of the resulting challenges is high loss-to-follow-up rates in HIV-infected patients who are not yet eligible for ART.

Difficulties with Adherence Among Patients on Treatment Sustaining high levels of adherence to ART is necessary for maintaining virologic control, staving off the development of drug resistance, and minimizing the need for switches to second-line therapy. Although high levels of adherence to ART were reported from many resource-constrained settings in the early years of ART implementation,10-12 the number of people in need of second-line ART has been growing steadily. A recent systematic review showed that almost a quarter of patients fail second-line therapy within 12 months, mainly because of suboptimal adherence rather than drug resistance.13 One of the most common reasons for nonadherence to ART is drug side effects. Until recently, d4T, which is associated with several common, severe adverse effects like lactic acidosis and peripheral neuropathy, was widely used in first-line ART regimens because of its low cost. However, d4T is progressively being replaced by tenofovir in the developing world.

Monitoring adherence and treatment success objectively with viral load is unaffordable in most of the developing world, despite studies demonstrating the benefits.14,15 As a result, HIV-infected patients in Africa tend to spend longer periods of time on failing regimens, thereby increasing the risk for development of drug resistance. The availability of affordable point-of-care diagnostic tests for CD4-cell count and viral load could have a huge effect in resource-constrained settings.

Improvements are needed in a number of areas, including the uptake of HIV testing, linkage to care, retention in care prior to ART eligibility, ART initiation in eligible patients, ART adherence, and retention of patients on ART. Substantial progress has been made during the past decade in scaling up ART, but much more remains to be done.

By Salim S. Abdool Karim, MD, PhD

Published in Journal Watch HIV/AIDS Clinical Care June 4, 2012

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15. Barth RE et al. Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. Antivir Ther 2012; 17:377.

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