To the Editors:
The prevalence of undiagnosed HIV infections and the characteristics of the undiagnosed infected individuals constitute useful data for adapting public health policy. In the United States, and in the United Kingdom, respectively, 21% and 24% of people living with HIV were unaware of their infection.1,2 In France, the only figure put forward is around 30% (representing 50,000 people).3 However this estimate includes both undiagnosed individuals and those aware of their infection but not followed up.
Various methods have been described to estimate the number of people with undiagnosed HIV infection, based either on prevalence surveys or on HIV/AIDS case reporting.4 Unlinked anonymous surveys can be of use in estimating the prevalence of HIV in both diagnosed and undiagnosed individuals.5
An anonymous survey among beneficiaries of the major National health insurance scheme (NHIS) was conducted in France in 2004 to estimate the prevalence of hepatitis B and C virus infections.6,7 The serum samples collected during this survey has been used retrospectively to estimate the prevalence of undiagnosed HIV infection by sex, age, sexual orientation, birthplace, and region of residence.
Each beneficiary of the French major NHIS is affiliated to a primary health insurance unit and can benefit from a free medical checkup in a social security medical centre (SSMC) further to a mail invitation. During this checkup, various clinical and biological tests are proposed. The study population for the hepatitis prevalence study was based on a random sample of beneficiaries aged 18–80 years in 2004, set up according to a 2-stage sampling design as follows:
- At the first stage, primary health insurance units and SSMC were stratified according to 5 regions and selected by unequal random sampling according to the size of SSMC activity.
- At the second stage, individuals affiliated to the selected primary health insurance units were selected using simple random sampling in 4 strata (<65 years, ≥65 years, whether or not they benefited from medical welfare for socially deprived persons). Selected subjects received an invitation by mail for a free medical checkup to be held in a SSMC, although explicitly mentioned the possibility to get an HIV test on demand during the checkup.
More than 14,000 subjects finally participated in the study. An anonymous questionnaire was completed which included sociodemographic data (sex, age, place of birth), information about social health coverage, hepatitis risk factors, and sexual orientation. An informed consent was requested for all participants.
Thirty months after the hepatitis study ended, the sera were sent to the HIV National Reference Centre. An HIV antigen–antibody screening test (fourth-generation enzyme-linked immunosorbent assay, Genscreen Plus Ag-Ab, Biorad, Marnes-la-coquette, France) was carried out for all sera, and any positive result was confirmed by Western Blot (HIV blot 2.2, MP Biomedicals, Singapore).
Data relating to HIV infection were analyzed taking into account the sampling design. Prevalence estimates were adjusted on age categories, sex, region, and medical welfare for socially deprived persons, using the 1999 French census data. Prevalence was estimated for heterosexuals, male homosexuals, and people born in France and in sub-Saharan Africa. The size of male homo/bisexuals and heterosexuals populations was estimated by combining French census data and the proportion of male homo/bisexuals and heterosexuals obtained from a national random survey of sexual behaviours.8
Of 14,416 participants in the hepatitis survey, 11,890 sera had been stored and were available for the HIV study (82% of all sera).
Of the 11,890 sera tested, 18 were identified as positive for HIV antibody (all anti-HIV-1 positive). The estimated HIV seroprevalence was 0.065% (Table 1), representing 29,008 persons aged 18–80 years in mainland France (95% confidence interval: 11,603 to 70,958).
Of the 18 HIV-infected individuals, 10 were born in sub-Saharan Africa and 4 were homo/bisexual men. Two heterosexual French men were found to be HIV positive. One man born in France (unknown sexual orientation) and 1 heterosexual woman born in Southern Europe were also found to be HIV positive. None of the 18 persons reported a previous history of injecting drug use.
Prevalence was estimated to be 0.041% in women and 0.09% in men. It was significantly higher in male homo/bisexuals compared with heterosexuals (1.7% vs. 0.05%) and significantly higher in persons born in sub-Saharan Africa compared with persons born in France (1.1% vs. 0.03%). Prevalence in the Paris region was 0.16% (13,000 persons) compared with 0.04% (16,000 persons) in the rest of mainland France.
The prevalence results issued from this study should be interpreted with caution as the methodology was initially designed to estimate the seroprevalence of hepatitis B and C. We cannot exclude selection biases if beneficiaries of the major NHIS differ from beneficiaries of other health insurance schemes (as self-employed people). However, these biases should be limited as on the one hand, this major scheme involves more than 80% of the population and on the other hand, estimates were adjusted on age, sex, and medical welfare, to represent the French metropolitan population. Participation biases could occur if participants in the study differ from nonparticipants. The note sent out with the invitation explicitly mentioned that an HIV test would be proposed, which has probably resulted in a participation bias.
The population of HIV-infected individuals can be divided into 3 categories: (1) individuals aware of their HIV infection and followed up regularly, (2) individuals aware of their HIV infection but not followed up, and (3) individuals unaware of their HIV infection.
We make the assumption that individuals followed up for their HIV infection, would not come for an additional free checkup because they already benefit from regular checkups.
We can also assume that individuals aware of their HIV infection but who are not in care (either not linked to care or lost to follow-up), may be less inclined to come for a medical checkup. Failure of linkage to care after diagnosis has been estimated around 25%9 and loss to follow-up has been estimated around 5% among patients attending HIV services one given year.10,11 The barriers of linkage to care and the reasons of loss to follow-up are multiple and probably include denial of HIV infection and distrust toward the care system.
Finally we assume that individuals who are not aware of their HIV infection would come to a free medical checkup with the same probability as the general population.
Under these hypotheses, the prevalence in this study is an estimation of the prevalence of undiagnosed HIV infection in France in 2004. This means that 29,000 persons (11,603–70,958) were unaware of their HIV-positive status. The estimate in the Paris region (0.16%) is consistent with a recent estimation of undiagnosed HIV prevalence in emergency departments (0.14%).12
Our hypotheses are reasonable but cannot be verified. If diagnosed but not followed up HIV-positive individuals have participated in the study, this would conduct to an overestimation of the undiagnosed HIV prevalence.
Our analysis has also made it possible to describe the individuals unaware of their HIV infection. Most of them (14/18) belonged to populations that are particularly exposed to HIV (persons born in sub-Saharan Africa, male homo/bisexuals) but not all (4 individuals not identified as belonging to high-risk group). None of the 18 HIV-positive individuals has reported history of injecting drug use. This finding is consistent with the fact that injecting drug users (IDUs) in France are mostly aware of their HIV status (the self-reported and biologically documented prevalence rates of HIV infection were identical in a National cross-sectional study among IDUs) and with the low number of new HIV diagnosis among IDUs (<100 cases every year).13,14
The estimated prevalence of undiagnosed HIV infections in France was 0.065% in 2004, corresponding to 29,000 persons (near half were living in the Paris region) and representing 19% of the estimated 150,000 people living with HIV in France,3 close to the estimation in United States and United Kingdom.1,2 It is consistent with the previous estimate in France (50,000 persons),3 which included both undiagnosed and diagnosed but not followed up people.
Given that the number of new HIV infections and those of new HIV diagnoses between 2004 and 2010 are similar (6000 to 7000 by year), the number of persons unaware of their HIV infection in 2010 is probably close to those estimated in 2004.14,15 Our study provides new results to estimate and characterize people undiagnosed for HIV and such results are key figures to improve screening strategies to allow earlier diagnosis and treatment of people who are unaware of their HIV status.
The authors thank M. J. Letort (Institut de veille sanitaire) and L. Yzon (HIV National Reference Centre, Tours).
1. Campsmith ML, Rhodes PH, Hall HI, et al.. Undiagnosed HIV prevalence among adults and adolescents in the United States at the end of 2006. J Acquir Immune Defic Syndr. 2010;53:619–624.
2. Health Protection Agency. Number of people living with HIV. In: Health Protection Agency, ed. HIV in the United Kingdom: 2011 Report. London, United Kingdom: Health Protection Services; 2011:5.
3. Costagliola D. Epidémiologie de l'infection à VIH. In: Yeni P, ed. Prise en charge médicale des personnes infectées par le VIH. Recommandations du Groupe d'Experts. Paris, France: La documentation française; 2010:24–33.
4. Working Group on Estimation of HIV Prevalence in Europe. HIV in hiding: methods and data requirements for the estimation of the number of people living with undiagnosed HIV. AIDS. 2011;25:1017–1023.
5. Nicoll A, Gill ON, Peckham C, et al.. The Public health application of unlinked anonymous seroprevalence monitoring for HIV in the United Kingdom. Int J Epidemiol. 2000;29:1–10.
7. Meffre C, Le Strat Y, Delarocque-Astagneau E, et al.. Prevalence of hepatitis B and hepatitis C virus infections in France in 2004: social factors are important predictors after adjusting for known risk factors. J Med Virol. 2010;82:546–555.
8. Bajos N, Bozon M, eds. Enquête sur la sexualité en France: pratiques, genre et santé. Paris, France: Editions La Découverte; 2008.
9. Centers for Disease Control and Prevention (CDC). Vital signs: HIV prevention through care and treatment—United States. MMWR Morb Mortal Wkly Rep. 2011;60:1618–1623.
10. Rice BD, Delpech VC, Chadborn TR, et al.. Loss to follow-up among adults attending human immunodeficiency virus services in England, Wales, and Northern Ireland. Sex Transm Dis. 2011;38:685–690.
11. Lanoy E, Lewden C, Lièvre L, et al.. How does loss to follow-up influence cohort findings on HIV infection? A joint analysis of the French hospital database on HIV, Mortalité 2000 survey and death certificates. HIV Med. 2009;10:236–245.
12. d'Almeida KW, Kierzek G, de Truchis P, et al.. Modest public health impact of nontargeted immunodeficiency virus screening in 29 emergency departments. Arch Intern Med. 2011;172:12–20.
13. Jauffret-Roustide M, Emmanuelli J, Quaglia M, et al.. Impact of a harm-reduction policy on HIV and hepatitis C virus transmission among drug users: recent French data—the ANRS-Coquelicot Study. Subst Use Misuse. 2006;41:1603–1621.
14. Cazein F, Le Strat Y, Pillonel J, et al.. Dépistage du VIH et découvertes de séropositivité, France, 2003–2010. Bull Epidémiol Hebd. 2011;43-44:446–454.
15. Le Vu S, Le Strat Y, Barin F, et al.. Population-based HIV-1 incidence in France, 2003-08: a modelling analysis. Lancet Infect Dis. 2010;10:682–687.