Controlling the HIV epidemic, without a vaccine!
DeGruttola, Victor; Little, Susan; Schooley, Robert
Harvard School of Public Health, Boston, Massachusetts, USA.
Received 29 July, 2008
Revised 11 September, 2008
Accepted 12 September, 2008
Correspondence to Professor Victor DeGruttola, DSc, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Tel: +1 617 432 2820; fax: +1 617 432 2832; e-mail: firstname.lastname@example.org
Despite recent failures of vaccines and microbicides , other developments in HIV prevention research give reason for optimism that the HIV epidemic may be controllable – made unsustainable – in some populations. To make full use of new knowledge and technology, efforts at HIV prevention must become more coordinated and focused on clearly defined goals, such as epidemic control, even in the absence of a vaccine.
The increased worldwide availability of HAART provides opportunities to decrease HIV transmission through several mechanisms. Reducing HIV RNA levels in plasma and genital secretions may diminish infectivity, as demonstrated in maternofetal transmission studies and a small, heterosexual transmission study . Studies of nosocomial transmission provide indirect evidence of the efficacy of postexposure prophylaxis (PEP); use of antiretroviral therapy (ART) to reduce risk of heterosexual transmission of HIV is under study. Several modeling studies strongly suggest that lowering the viral load reduces risk of HIV transmission , although current treatment guidelines limit access to therapy for this purpose. Current guidelines do, however, encourage testing for HIV infection, thereby providing opportunities for interventions to reduce transmission. Abstinence promotion, herpes simplex virus 2 suppressive treatment, protective immunization, and topical microbicides (studies of ART as microbicide are underway) have not shown much promise in randomized trials, but male circumcision and treatment of concurrent sexually transmitted diseases  have shown more promise, as have studies of behavioral interventions such as promoting condom use [5,6]. More broadly, measures such as identification and treatment of people during periods of high infectiousness, education regarding transmission, vigorous contact tracing, and population screening have had major impact on many diseases for which no vaccine is available, including syphilis and tuberculosis .
The efficacy of rollout of HAART (and high observed levels of compliance), in developing countries, demonstrates what is achievable through coordinated efforts of governments and nongovernmental organizations (NGOs), aided by lower cost and more widely available laboratory monitoring techniques. Although most research on HIV transmission has focused on chronically infected patients, the importance of the acutely infected is being increasingly recognized [8–10]. Furthermore, the feasibility of identifying individuals with acute or very early infection has been much increased by the success of methods for pooling the required tests, even in relatively low prevalence areas [11–16]. The increased cost of earlier initiation of HAART, though considerable, might, over time, be far outweighed by benefits of reduced transmission. Because HAART therapy extends life and treatment duration – perhaps by decades  – preventing new cases is imperative for cost containment. Consider the simple example of a population with an HIV prevalence of 1000 and an effective HIV reproductive rate above one, that is, 1000 infected people are expected to give rise to at least as many new infections. Suppose patients were to initiate treatment an average of 5 years earlier, adding 5000 person-years of treatment for the original prevalent cohort. Compensating for this additional treatment requires reducing the number of new infections by N = 5000/Y, in which Y is the average duration of treatment. For example, for Y = 25, P = 200, corresponding to no more than a 20% reduction in the number of new cases arising from the original 1000 patients, and preventing each new infection may in turn prevent chains of transmission. The need for lifelong treatment imposes a considerable burden; however, as with gonorrhea and syphilis, focus on acute or very early HIV infection or on those known to have transmitted virus or both, may be the most cost-effective way to target therapy. Given the higher risk of transmission during primary infection that could lead to higher effective reproductive rates , cost effectiveness might be enhanced by interrupting treatment of the acutely infected after 1 year and resuming when guidelines are met. Similarly, even if early treatment causes some resistance, this practice might still lead to reduced prevalence of resistant infections if it sufficiently reduces HIV incidence. Appropriate studies are needed to assess costs and benefits of treatment policies in different settings.
Epidemic modeling should also be used to explore synergies and tailor interventions for local conditions. For example, in settings where wives, but not husbands, tend to be monogamous, it may be most cost effective to concentrate efforts on commercial sex workers. Modeling surveillance data makes it possible to monitor whether or not populations are on track to achieve control – information that might be fed back to communities to encourage participation in prevention efforts. Implementation of even only modestly effective, but synergistic, interventions, might make controlling the HIV epidemic a realistic goal.
Achieving the desired level of coordination will not be easy. But it will be necessary for epidemic models to be useful in investigating the impact of interventions and proposing new ones, suggesting research studies or surveillance methods to improve model inputs, and identifying the most cost-effective deployment of resources. Modelers must coordinate their efforts with those needed to mount studies, launch interventions, and evaluate cost effectiveness. Although a safe and effective vaccine must remain a major goal of AIDS research, it is unwise to plan epidemic control efforts on the premise that this goal is reachable, given the daunting challenges to be overcome. While vaccine research proceeds, we must exploit scientific advances already achieved; the means to control the HIV epidemic may already be within our grasp.
All authors contributed opinions and ideas to this paper.
1. Lagakos S, Gable A. Challenges to HIV prevention-seeking effective measures in the absence of a vaccine. N Engl J Med 2008; 358:1543–1545.
2. Castilla J, Del Romero J, Hernando V, Marincovich B, Garcia S, Rodriguez C. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr 2005; 40:96–101.
3. Phillips AN, Sabin C, Pillay D, Lundgren JD. HIV in the UK 1980-2006: reconstruction using a model of HIV infection and the effect of antiretroviral therapy. HIV Med 2007; 8:536–546.
4. Grosskurth H, Mosha F, Todd J, Mwijarubi E, Klokke A, Senkoro K, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995; 346:530–536.
5. Pinkerton SD, Abramson PR. Effectiveness of condoms in preventing HIV transmission. Soc Sci Med 1997; 44:1303–1312.
6. Davis KR, Weller SC. The effectiveness of condoms in reducing heterosexual transmission of HIV. Fam Plann Perspect 1999; 31:272–279.
7. Hogben M, McNally T, McPeeters, Hutchinson AB. The effectiveness of HIV partner counseling and referral services in increasing identification of HIV-positive individuals a systematic review. Am J Prev Med 2007; 33 (2 Suppl):S89–S100.
8. Wawer M, Serwadda D, Quinn T, et al. Reply to Gisselquist and Potterat. J Infect Dis 2005; 192:1499–1500.
9. Brenner BG, Roger M, Routy JP, Moisi D, Ntemgwa M, Matte C, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 2007; 195:951–959.
10. Lewis F, Hughes GJ, Rambaut A, Pozniak A, Leigh Brown AJ. Episodic sexual transmission of HIV revealed by molecular phylodynamics. PLoS Med 2008; 5:e50.
11. Pilcher C, Fiscus SA, Nguyen TQ, Foust E, Wolf L, Williams D, et al. Detection of acute infections during HIV testing in North Carolina. N Engl J Med 2005; 352:1873–1883.
12. Stekler J, Collier AC, Holmes KK, Golden M. Primary HIV infection education: knowledge and attitudes of HIV-negative men who have sex with men attending a public health sexually transmitted disease clinic. J Acquir Immune Defic Syndr 2006; 42:123–126.
13. Klausner JD, Grant RM, Kent CK. Detection of acute HIV infections. N Engl J Med 2005; 353:631–633.
14. Patel P, Klausner JD, Bacon O, Liska S, Taylor M, Gonzalez A, et al. Detection of acute HIV infections in high-risk patients in California. J Acquir Immune Defic Syndr 2006; 42:75–79.
15. Priddy F, Pilcher C, Moore R, Tambe P, Park MN, Fiscus SA, et al. Detection of acute HIV infections in an urban HIV counseling and testing population in the United States. J Acquir Immune Defic Syndr 2007; 44:196–202.
16. Truong H-HM, Grant RM, McFarland W, Kellogg T, Kent C, Louie B, et al. Routine surveillance for the detection of acute and recent HIV infections and transmission of antiretroviral resistance. AIDS 2006; 20:2193–2197.
17. Schackman BR, Gebo KA, Walensky RP, Losina E, Muccio T, Sax PE, et al. The lifetime cost of current human immunodeficiency virus care in the United States. Med Care 2006; 44:990–997.
18. Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission by stage of infection. J Infect Dis 2008; 198:687–693.
© 2008 Lippincott Williams & Wilkins, Inc.