Elsevier

The Lancet

Volume 373, Issue 9657, 3–9 January 2009, Pages 48-57
The Lancet

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Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model

https://doi.org/10.1016/S0140-6736(08)61697-9Get rights and content

Summary

Background

Roughly 3 million people worldwide were receiving antiretroviral therapy (ART) at the end of 2007, but an estimated 6·7 million were still in need of treatment and a further 2·7 million became infected with HIV in 2007. Prevention efforts might reduce HIV incidence but are unlikely to eliminate this disease. We investigated a theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, and examined the conditions under which the HIV epidemic could be driven towards elimination.

Methods

We used mathematical models to explore the effect on the case reproduction number (stochastic model) and long-term dynamics of the HIV epidemic (deterministic transmission model) of testing all people in our test-case community (aged 15 years and older) for HIV every year and starting people on ART immediately after they are diagnosed HIV positive. We used data from South Africa as the test case for a generalised epidemic, and assumed that all HIV transmission was heterosexual.

Findings

The studied strategy could greatly accelerate the transition from the present endemic phase, in which most adults living with HIV are not receiving ART, to an elimination phase, in which most are on ART, within 5 years. It could reduce HIV incidence and mortality to less than one case per 1000 people per year by 2016, or within 10 years of full implementation of the strategy, and reduce the prevalence of HIV to less than 1% within 50 years. We estimate that in 2032, the yearly cost of the present strategy and the theoretical strategy would both be US$1·7 billion; however, after this time, the cost of the present strategy would continue to increase whereas that of the theoretical strategy would decrease.

Interpretation

Universal voluntary HIV testing and immediate ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics. This approach merits further mathematical modelling, research, and broad consultation.

Funding

None.

Introduction

25 years after the discovery of HIV,1 control of the HIV epidemic remains elusive and some have called for a re-examination of the approach to control this virus.2 Development of an effective HIV-1 vaccine remains a remote possibility, and trials of vaginal microbicides have not shown any protective benefit.3, 4 Where HIV transmission is mainly heterosexual, male circumcision can reduce adult heterosexual HIV transmission, but only by about 40% at the overall population level.5, 6 A call has been made to focus prevention interventions on high-risk populations7 and to expand programmes for female sex workers and their clients,8 and injecting drug users.9 Few people are aware of their HIV status, and rapid expansion of voluntary HIV testing and counselling has been recommended by WHO.10 About 3 million people worldwide had been given antiretroviral therapy (ART) at the end of 200710 but an estimated 6·7 million were still in need of it and a further 2·7 million were infected with HIV in 2007.10, 11, 12

At present there is inadequate evidence for WHO to provide guidance on the role of ART for people living with HIV as a strategy to prevent further sexual transmission. To control the HIV/AIDS epidemic, infectious individuals would have to be rendered non-infectious, or susceptible people protected from infection. Vertical transmission of HIV can be eliminated by testing of mothers and blocking of transmission through the use of antiretroviral drugs, accompanied by elective caesarean section and the use of replacement infant feeding.13 Although increasing emphasis is being placed on positive prevention14, 15 and provider-initiated HIV testing and counselling,16 no large-scale studies have been undertaken of the effect of diagnosing all HIV-positive people early and treating them immediately.

Present guidelines suggest that ART should be started when infected people reach specific immunological or clinically-defined stages of disease to keep subsequent morbidity and mortality in individual patients to a minimum.17 Wherever ART has been implemented it has had a substantial and rapid effect on survival for individuals and within populations.18 The effect of treatment on transmission and the possible public-health benefits have, with some exceptions, received less attention.19, 20, 21, 22 The use of ART can reduce the plasma viral load by up to six orders of magnitude,23 and several investigators have assessed the effect of ART on transmission.19, 20, 24 However, the high viral load during the acute phase of infection, the long duration of infectiousness, the present policy of limiting costly and potentially toxic ART to people whose immune systems are severely compromised, and low coverage can reduce the extent to which the use of ART reduces transmission.

Despite substantial efforts to expand access to voluntary HIV testing, nearly 80% of HIV-infected adults in sub-Saharan Africa are unaware of their status and more than 90% do not know whether their partners are infected with HIV.10, 25 Present approaches to HIV testing, prevention, and treatment are unlikely to bring about a rapid reduction in HIV incidence, and demand for treatment in countries that are most heavily affected will continue to grow. Reduction in HIV incidence, with the goal of eventual elimination, would require that the case reproduction number R0—the number of secondary infections resulting from one primary infection in an otherwise susceptible population—is reduced to and kept below 1.26 A potential shift in strategy is to diagnose all HIV-infected people as soon as possible after infection and provide them with immediate ART. In considering the use of ART to eliminate transmission, we focused on two questions: how often would people have to be tested and how soon after testing positive should they start ART? In this hypothetical modelling exercise, we examined a strategy of universal voluntary HIV testing and immediate treatment with ART in the context of a generalised heterosexual epidemic of the same intensity as in southern Africa, and examined the conditions under which the epidemic could be driven towards elimination. The results have potential implications for HIV prevention that require broad consultation.

Section snippets

Study design

To establish a hypothetical HIV epidemic, we relied on available data from South Africa as the test case for a generalised HIV epidemic, representing 17% of all people living with HIV.11 Our hypothetical test case assumed, as in South Africa, that almost all transmission was heterosexual rather than homosexual. This assumption holds true for South Africa and similar settings, and was supported by the observation that the prevalence of HIV in South African men is estimated to be 58% of the

Results

Figure 3 shows results from the stochastic model as contours of R0 plotted against the CD4+ cell count at which ART would start and the frequency of testing. To reduce R0 to less than 1 (green area), adolescents and adults would need to be tested at least once per year and started on ART when their CD4+ count is greater than 900 cell per μL. In South Africa, the average value of the CD4+ count immediately after seroconversion is about 884 cells per μL,29 so most adolescents and adults would

Discussion

The results show that universal voluntary HIV testing once a year of all people older than 15 years, combined with immediate ART after diagnosis, could bring about a phase change in the nature of the epidemic. Instead of dealing with the constant pressure of newly infected people, mortality could decrease rapidly and the epidemic could begin to resemble a concentrated epidemic with particular populations remaining at risk. The focus of control would switch from making ART available to people

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