The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study

Summary

Background

HIV transmission risk is higher during acute and early HIV infection than it is during chronic infection, but the contribution of early infection to the spread of HIV is controversial. We estimated the contribution of early infection to HIV incidence in Lilongwe, Malawi, and predict the future effect of hypothetical prevention interventions targeted at early infection only, chronic infection only, or both stages.

Methods

We developed a deterministic mathematical model describing heterosexual HIV transmission, informed by detailed behavioural and viral-load data collected in Lilongwe. We included sexual contact within and outside of steady pairs and divided the infectious period into intervals to allow for changes in transmissibility by infection stage. We used a Bayesian melding approach to fit the model to HIV prevalence data collected between 1987 and 2005 at Lilongwe antenatal clinics. We assessed interventions that reduced the per-contact transmission probability to 0·00003 in people receiving them, and varied the proportion of individuals receiving the intervention in each stage.

Findings

We estimated that 38·4% (95% credible interval 18·6–52·3) of HIV transmissions in Lilongwe are attributable to sexual contact with individuals with early infection. Interventions targeted at only early infection substantially reduced HIV prevalence, but did not lead to elimination, even with 100% coverage. Interventions targeted at only chronic infections also reduced HIV prevalence, but coverage levels of 95–99% were needed for the elimination of HIV. In scenarios with less than 95% coverage of interventions targeted at chronic infections, additional interventions reaching 25–75% of individuals with early infection reduced HIV prevalence substantially.

Interpretation

Our results suggest that early infection plays an important part in HIV transmission in this sub-Saharan African setting. Without near-complete coverage, interventions during chronic infection will probably have incomplete effectiveness unless complemented by strategies targeting individuals with early HIV infection.

Funding

National Institutes of Health, University of North Carolina Center for AIDS Research.

Introduction

Acute HIV infection is the period between HIV acquisition and the development of detectable antibodies against the virus. Early HIV infection, including acute infection, is characterised by rapid viral replication, intense immune response and immune destruction, and viral diversification.¹ Phenotypic factors unique to the founder virus or viruses causing infection,² along with high viral loads,3, 4 result in greater transmission risk during early infection than during chronic stages of infection.5, 6, 7, 8

The population-level effect of transmission prevention efforts during early infection will vary across settings, dependent on the contribution of individuals with early infection to epidemic spread. Estimates of this contribution have varied widely,6, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 dependent on site-specific factors such as risk behaviour patterns and the local epidemic stage. In the past 2 years, a strategy to use mass antiretroviral treatment to stop the spread of HIV-1 has gained much attention.¹⁹ This test-and-treat strategy advocates regular, widespread HIV testing and immediate initiation of antiretroviral treatment for infected people and is based on the premise that reductions in viral load caused by antiretroviral treatment will decrease an individual's infectiousness. However, the population-level effectiveness of this approach will depend partly on the role of early infection in continuing virus transmission: when it has a major role, the effectiveness of test-and-treat strategies will probably be restricted, unless patients with early infection can be detected and included. The findings from a mathematical modelling study¹⁹ that have prompted much controversy20, 21, 22, 23, 24, 25, 26, 27, 28, 29 suggest that a yearly test-and-treat strategy could eliminate HIV, but concerns have been expressed that the importance of early infection was underestimated in this model.22, 24, 25

In this study, we estimated the contribution of early infection to HIV spread in Lilongwe, Malawi, where HIV-1 is hyperendemic and transmission is almost entirely through heterosexual contact. We also examined the population-level effect of prevention interventions affecting only early infection, only chronic infection, or both, with an emphasis on estimation of the effect of a yearly test-and-treat strategy.¹⁹ To address these aims, we used empirical data from our studies in Lilongwe3, 30 to develop a mathematical model describing heterosexual HIV transmission.