HIV

Acquired Immunodeficiency Syndrome (AIDS) is the most severe outcome of an untreated HIV infection. AIDS presents with severe opportunistic infections, malignancies, neurological complications or other HIV-induced disease conditions (Del Rio & Curran, 2005). After infection with HIV, individuals may remain asymptomatic or develop Acute Retroviral Syndrome (ARS) (Del Rio & Curran, 2005). ARS occurs in 50–66% of all recently infected cases (Sterling & Chaisson, 2005). Due to mild and non-specific flu-like symptoms many people do not seek medical advice, and thus are not diagnosed and treated and proceed to a latent stage where they may remain asymptomatic for years before subsequently developing AIDS.

Within the EU, it is estimated that around 8–45% of all HIV infections are undiagnosed and therefore not reported to the health authorities (ECDC, 2014). The overall duration is difficult to estimate because since introduction of Anti-Retroviral Therapy (ART) HIV is increasingly observed as being a chronic disease and individuals receiving treatment have a similar life expectancy to the rest of the population in Europe (Bhaskaran, 2008). Persistent asymptomatic HIV infection is estimated to be on average 17.2 years for long-term non-progressors (Herida, 2006).

Health outcomes/states associated with HIV-infection

HIV is associated with a heterogeneous set of health outcomes/states. In most cases, certain health outcomes/states are caused by subsequent infections with a secondary or tertiary pathogen. HIV compromises the immune status of an individual and thus increases the risk of further additional pathogens causing severe sequelae.

For our study, we considered that in Europe development of AIDS is significantly limited through ART.

HIV/AIDS is a complicated, multi-faceted and systemic disease and for reasons of feasibility, we developed a simplified model which does not differentiate between the CD4 count stages of the disease at the point of diagnosis, even though this is known to affect mortality (Aghaizu, 2013). Moreover, the current model does not take into account transmitted drug resistance, or the issue of co-morbidity (HIV–HCV or HIV–TB) and the consequent need for a specific therapeutic pathway. We assumed that all diagnosed cases are offered treatment and we applied a certain burden to the disease (e.g. side effects).

HIV infection-related deaths are associated with the development of an acquired immunodeficiency syndrome (AIDS) which, after a prolonged latent period, eventually enables opportunistic infections to develop which are generally the cause of death. Therefore, the nature of AIDS itself consists of comorbidities introducing the issue of attributable cause of death. However, we assumed that the severity of the co-infection and the precipitation to death would not have occurred without the primary HIV infection and deaths were therefore attributed entirely to the initial HIV infection. We also did not include the burden associated with HIV-related malignancies or complications linked to long-term antiretroviral therapy (e.g. cardiovascular disease).

Outcome-tree parameters

The main input is ‘persistent HIV infection’ and this is subdivided according to the speed of progression (Qu, 2008). In general, 5–15% of all patients are rapid progressors (RP) and are at risk of developing AIDS within 2–5 years (Qu, 2008). Another 5–15% are long-term non-progressors (LNP) with, on average 17.2 years duration of development (Qu, 2008; Sterling & Chaisson, 2005). The remainder (70–90%) are typical progressors (TP) with an average duration of 8–10 years (Qu, 2008).

The risk of developing early symptomatic AIDS is set at between 4.5% and 7% (Grinsztejn, 2014: 40 observed cases out of 886 in the group with early ART initiation versus 61 out of 877 in the delayed group).

Terminal AIDS has a duration of one month (Kwong, 2010) and the risk of developing terminal AIDS from early symptomatic AIDS is set at 32.09% as this was the case fatality proportion estimated for AIDS in a recent study (Serraino, 2010).

Model input summary

Table 1. Transition probabilities and distributions used in the outcome tree

 Health outcome
 (Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Persistent HIV infection

(Rapid progressors)
(Typical progressors)
(Long-term non-progressors)

 

5–15%
70–90%
5–15%

 

No cure available

Qu, 2008
Qu, 2008
Qu, 2008; Herida, 2006

AIDS early symptomatic

 

4.5–7%

Grinsztejn, 2014

AIDS terminal phase

 

32.09%

Serraino, 2010

CFR from AIDS

 

100%

 

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source

Persistent HIV infection

(Rapid progressors)
(Typical progressors)
(Long-term non-progressors)

0.108
(0.089-0.132)

HIV/AIDS cases, receiving ARV treatment

 


2-5
8-10
17.2

 


Qu, 2008
Qu, 2008
Qu, 2008; Herida, 2006

Permanent ARV treatment

0.108
(0.089-0.132)

HIV/AIDS cases, receiving ARV treatment

Remaining life expectancy

Assuming ARV treatment has optimal effectiveness and good compliance

AIDS early symptomatic

0.351
(0.299–0.394)

HIV cases, symptomatic, pre-AIDS

5.36

Herida, 2006

AIDS terminal phase

0.574
(0.518–0.635)

AIDS cases, not receiving ARV treatment

0.08

Kwong, 2010

References

Aghaizu A, Brown AE, Nardone A, Gill ON, Delpech VC & contributors. HIV in the United Kingdom 2013 - Report: data to end 2012. November 2013. Public Health England, London. Available at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/326601/HIV_annual_report_2013.pdf

Barre-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983, 220:868-871.

Bhaskaran K, Hamouda O, Sannes M, Boufassa F, Johnson AM, Lambert PC, et al. for the CASCADE Collaboration. Changes in the Risk of Death After HIV Seroconversion Compared With Mortality in the General Population. JAMA. 2008;300(1):51-59. doi:10.1001/jama.300.1.51.

Cameron DW, Simonsen JN, D'Costa LJ, Ronald AR, Maitha GM, Gakinya MN, et al. Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men. Lancet 1989, 2:403-407.

Cleghorn FR, Reits Jr. MS, Popovic M, Gallo RC. Human Immunodeficiency Viruses. In Principles and Practice of Infectious Diseases. Volume 2. Edited by Mandell GL, Bennet JE, Dolin R. Pennsylvania: Elsevier Inc.; 2005: 2119-2132

HIV/AIDS. Available at: http://www.who.int/topics/hiv_aids/en/

Del Rio C, Curran JW. Epidemiology and Prevention of Acquired Immunodeficiency Virus Infection. In Principles and Practice of Infectious Diseases. Volume 1. Edited by Mandell GL, Bennet JE, Dolin R. Pennsylvania: Elsevier Inc.; 2005: 1477-1506

European Centre for Disease Prevention and Control. Monitoring implementation of the Dublin Declaration on Partnership to Fight HIV/AIDS in Europe and Central Asia: 2014 progress report, in press.

Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M, Richardson E, Kalyanaraman VS, et al. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 1983, 220:865-867.

Grinsztejn B, Hosseinipour M, Ribaudo H, Havlir D, Cohen M, et al. (2014). Effects of Early versus Delayed Initiation of Antiretroviral Therapy on HIV Clinical Outcomes: Results from the HPTN 052. The Lancet Infectious Diseases, Volume 14, Issue 4, April 2014, Pages 281-290

Haagsma JA, Maertens de Noordhout C, Polinder S, Vos T, Havelaar AH, Cassini A, Devleesschauwer B, Kretzschmar ME, Speybroeck N, Salomon JA. Assessing disability weights based on the responses of 30,660 people from four European countries. Population Health Metrics 2015; 13: 10

Herida M, Larsen C, Lot F, Laporte A, Desenclos JC, Hamers FF. Cost-effectiveness of HIV post-exposure prophylaxis in France. AIDS 2006, 20:1753-1761.

Kwong JC, Crowcroft NS, Campitelli MA, Ratanasingham S, Daneman N, Deeks SL, et al. Ontario Burden of Infectious Disease Study. In: Ontario Burden of Infectious Disease Study (ed.), Vol. OAHPP/ECES Report. City: Ontario Agency for Health Protection and Promotion and the Institute for Clinical Evaluative Sciences; 2010.

Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N,et al. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 1993, 7:95-102.

Merson MH, Piot P. Global Perspectives on Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome. In Principles and Practice of Infectious Diseases. Volume 1. Edited by Mandell GL, Bennet JE, Dolin R. Pennsylvania: Elsevier Inc.; 2005: 1456-1506

Qu W, Robinson M, Zhang FJ. Factors influencing the natural history of HIV-1 infection. Chin Med J (Engl) 2008, 121:2613-2621.

Serraino D, Bruzzone S, Zucchetta A, Suligoi B, De Paoli A, Pennazza S, et al. Elevated risks of death for diabetes mellitus and cardiovascular diseases in Italian AIDS cases. AIDS Research and Therapy 2010, 7(11)

Sterling TR, Chaisson RE: General Clinical Manifestations of Human Immunodeficiency Virus Infection (Including the Acute Retroviral Syndrome and Oral, Cutaneous, Renal, Ocular and Cardia Diseases). In Principles and Practice of Infectious Diseases. Volume 1. Edited by Mandell GL, Bennet JE, Dolin R. Pennsylvania: Elsevier Inc.; 2005: 1547-1574