Two randomized trials recently documented important clinical benefits of very early antiretroviral therapy (ART) [1,2]. These results complemented previous evidence of the preventive effect of early ART [3], so that treatment and prevention can now be seen as converging goals. Beyond preventive and clinical effects of early ART initiation, its possible consequences on social dimensions of patients’ lives remain to be documented.
Pathways linking ART initiation to repercussion on various social dimensions are complex and partially understood. ART initiation is associated with HIV status disclosure to relatives [4–6], which in turn not only lead to increased social support, but also to rejection [7,8]. Similarly, the impact of ART on stigma and discrimination seems ambiguous [9–11]. Positive impact on professional activity has been more consistently documented [12,13]. However, these associations have been observed among people initiating ART at low CD4+ cell count or with HIV-related symptoms. Negative events associated with ART may be more likely among people with high CD4+ cell count, among whom treatment initiation may reveal a hitherto unapparent HIV infection.
With new international guidelines recommending ART for every HIV-infected person, trends should progressively move toward earlier treatment initiation [14]. The social repercussions of ART initiation among people perceiving themselves, or being perceived by their relatives, as healthy have not been documented yet, although they may have a substantial impact on acceptation and adherence, and ultimately on the public health impact of this strategy.
Relying on social data collected within the TEMPRANO-ANRS12136 randomized controlled trial, we aimed to assess the impact of early ART on various dimensions reflecting social inclusion and the experience of discrimination.
The present socio-behavioral study was nested in the TEMPRANO-ANRS12136 trial, a randomized trial of early ART that was conducted in Abidjan (Côte d’Ivoire) [1,15]. At inclusion, ART-naïve participants presenting no criteria for starting ART were randomized to initiate ART immediately (‘early ART’) or to defer ART until ongoing WHO criteria for treatment initiation were met (‘deferred ART’) [16,17]. Standardized socio-behavioral questionnaires were completed during face-to-face interviews conducted at inclusion and then during clinical visits occurring around 12 and 24 months after inclusion.
Questionnaires included items related to household composition, couple status, HIV status disclosure inside and outside the household, professional activity and experience of discriminations. From these items, we constructed the following indicators: living alone (yes/no), being in union (yes/no), having disclosed HIV status inside (yes/no) or outside (yes/no) the household, having had a regular professional activity in the last 6 months (yes/no) and having experienced HIV-related discriminations in the last 12 months (yes/no).
All trial participants having completed a questionnaire at one or more of the following timings were included in the analysis: M0 (inclusion visit), M12 (12 ± 3 months after inclusion) and M24 (24 ± 6 months after inclusion). For each indicator, levels and time trends from M0 to M24 were assessed and compared between deferred and early ART groups. Generalized estimating equations with a logit link were used to account for multiple observations. Models included ART group and time period (coded as a three-level factor: M0/M12/M24) as covariates. Interaction terms between ART group and time period were added in order to test differential time trends between ART groups.
A total of 2061 participants (deferred ART: 1028 and early ART: 1033) completed at least one socio-behavioral questionnaire (Table S1, https://links.lww.com/QAD/A910). Median baseline CD4+ cell count was 469 cells/μl (IQR 379–577), 91% were WHO stage 1 or 2. After randomization, participants’ socio-demographic and clinical characteristics distributions were balanced between both groups (Table S2, https://links.lww.com/QAD/A910).
Levels and time trends in social indicators according to ART strategy are presented in Fig. 1. Twenty-four months after inclusion, we did not observe any significant differences in the level reported by participants between the early and deferred ART group for any of the indicators (Table S3, https://links.lww.com/QAD/A910). The interaction term between randomization group and time was not significant for any of the indicators (each P more than 0.25), suggesting that the observed time trends between M0 and M24 were not significantly different between ART strategies (Table S4, https://links.lww.com/QAD/A910). Results were similar when stratifying the analysis by sex (Table S5).
;)
Fig. 1: Social indicators reported at inclusion (M0), 12-month (M12) and 24-month (M24) visits among participants on deferred versus early antiretroviral therapy (ART).Percentages and 95% confidence intervals are computed using generalized estimating equations.
Motivation to start and adhere to ART may be difficult for people at early stage of HIV infection [18,19]. By increasing the visibility of HIV infection among apparently healthy people, one could have feared that early ART would lead to HIV disclosure and potentially to discrimination, union breaking and loneliness. Moreover, adverse consequences on occupational activity could have been expected because of potential side effects of ART [20]. Documenting the absence of detectable associated negative social events is thus reassuring with regard to the social feasibility of very early ART and may help remove barriers to enter into treatment.
The study reports an absence of evidence supporting adverse social effect of early ART. Several elements suggest that, had substantial effects existed, this study would have successfully detected them. First, we relied on a large sample size that would have allowed detecting even small effect sizes. Second, information was collected face-to-face by trained interviewers using standardized questionnaires. Randomization ensured an equivalent distribution of confounders between the control and intervention groups. As follow-up was similar in both groups, differential report bias appears unlikely. However, the studied indicators did not cover key socio-behavioral issues such as intimate partner violence or mental health. Monitoring the implementation of the updated recommendations for ART initiation may help assess these issues.
To our knowledge, no previous study has addressed the issue of the repercussion of early ART on diverse social dimensions. These results have been obtained within a trial that documented strong clinical individual benefits of early ART alongside evidence for reduced sexual risk behaviors following early entry into care and decreased risk of transmission due to the effect of ART on viral load [1,15,21]. As a whole, these results show that early ART in a west African context appears to combine clinical and preventive benefits that are not impaired by potential adverse social effects. This reinforces the relevance of generalized recommendations of ART initiation as soon as possible for HIV-infected people in Africa.
Acknowledgements
We are indebted to all patients who participated in this trial.
A.D.L., F.L., R.D.S. and C.D. designed the research and obtained funds. R.M., G.M.K. and A.B. contributed to acquisition of data. C.D., R.M., S.E. and X.A. supervised the study. K.J., S.N., C.D., R.D.S., F.L. and A.D.L. contributed to study concept and design. S.N., K.J. and D.G. prepared and analysed the data. K.J., S.N. and A.D.L. performed the literature research and drafted the manuscript. C.D., R.M., R.D.S., S.E., F.L. and X.A. critically revised the manuscript for important intellectual content.
Source of support: This trial was supported by the French Agence Nationale de Recherches sur le SIDA et les hépatites virales (ANRS), Paris, France [ANRS 12136 and ANRS 12239]. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Conflicts of interest
There are no conflicts of interest.
References
1. Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, et al. TEMPRANO ANRS 12136 Study Group.
A trial of early antiretrovirals and isoniazid preventive therapy in Africa.
N Engl J Med 2015; 373:808–822.
2. Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, et al. INSIGHT START Study Group.
Initiation of antiretroviral therapy in early asymptomatic HIV infection.
N Engl J Med 2015; 373:795–807.
3. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al.
Prevention of HIV-1 infection with early antiretroviral therapy.
N Engl J Med 2011; 365:493–505.
4. Vu L, Andrinopoulos K, Mathews C, Chopra M, Kendall C, Eisele TP.
Disclosure of HIV status to sex partners among HIV-infected men and women in Cape Town, South Africa.
AIDS Behav 2012; 16:132–138.
5. Linda P.
To tell or not to tell: negotiating disclosure for people living with HIV on antiretroviral treatment in a South African setting.
SAHARA J 2013; 10 (suppl 1):S17–S27.J Soc Asp HIVAIDS Res Alliance SAHARA Hum Sci Res Counc.
6. Haberlen SA, Nakigozi G, Gray RH, Brahmbhatt H, Ssekasanvu J, Serwadda D, et al.
Antiretroviral therapy availability and HIV disclosure to spouse in Rakai, Uganda: a longitudinal population-based study.
JAIDS J Acquir Immune Defic Syndr 2015; 69:241–247.
7. Tijou Traoré A, Querre M, Brou H, Leroy V, Desclaux A, Desgrées-du-LoÛ A.
Couples, PMTCT programs and infant feeding decision-making in Ivory Coast.
Soc Sci Med 2009; 1982: 69:830–837.
8. Henry E, Bernier A, Lazar F, Matamba G, Loukid M, Bonifaz C, et al.
Was it a mistake to tell others that you are infected with HIV?: factors associated with regret following HIV disclosure among people living with HIV in five countries (Mali, Morocco, Democratic Republic of the Congo, Ecuador and Romania). Results from a community-based research.
AIDS Behav 2014; doi: 10.1007/s10461-014-0976-8; Published Online First.
9. Pearson CR, Micek MA, Pfeiffer J, Montoya P, Matediane E, Jonasse T, et al.
One year after ART initiation: psychosocial factors associated with stigma among HIV-positive mozambicans.
AIDS Behav 2009; 13:1189–1196.
10. Roura M, Urassa M, Busza J, Mbata D, Wringe A, Zaba B.
Scaling up stigma? The effects of antiretroviral roll-out on stigma and HIV testing. Early evidence from rural Tanzania.
Sex Transm Infect 2009; 85:308–312.
11. Tsai AC, Bangsberg DR, Bwana M, Haberer JE, Frongillo EA, Muzoora C, et al.
How does antiretroviral treatment attenuate the stigma of HIV? Evidence from a cohort study in rural Uganda.
AIDS Behav 2013; 17:2725–2731.
12. Rosen S, Larson B, Brennan A, Long L, Fox M, Mongwenyana C, et al.
Economic outcomes of patients receiving antiretroviral therapy for HIV/AIDS in South Africa are sustained through three years on treatment.
PLoS One 2010; 5: doi:10.1371/journal.pone.0012731.
13. Bor J, Tanser F, Newell M-L, Bärnighausen T.
In a study of a population cohort in South Africa, HIV patients on antiretrovirals had nearly full recovery of employment.
Health Aff (Millwood) 2012; 31:1459–1469.
14. WHO.
Guideline on when to start antiretroviral therapy and on preexposure prophylaxis for HIV. 2015; Geneva, Switzerland: WHO,
http://www.who.int/entity/hiv/pub/guidelines/earlyrelease-arv/en/http://www.who.int/entity/hiv/pub/guidelines/earlyrelease-arv/en/ (accessed 6 Oct2015).
15. Jean K, Gabillard D, Moh R, Danel C, Desgrées-du-LoÛ A, N’takpe J-B, et al.
Decrease in sexual risk behaviours after early initiation of antiretroviral therapy: a 24-month prospective study in Côte d’Ivoire.
J Int AIDS Soc 2014; 17:18977.
16. WHO.
Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach: 2006 revision. 2006; Geneva: World Health Organisation,
http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf
17. WHO.
Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach: 2010 revision. 2010; Geneva: World Health Organisation,
http://www.who.int/hiv/pub/arv/adult2010/en/index.htmlhttp://www.who.int/hiv/pub/arv/adult2010/en/index.html (accessed 6 Mar2013).
18. Katz IT, Essien T, Marinda ET, Gray GE, Bangsberg DR, Martinson NA, et al.
Antiretroviral therapy refusal among newly diagnosed HIV-infected adults.
AIDS Lond Engl 2011; 25:2177–2181.
19. Katz IT, Dietrich J, Tshabalala G, Essien T, Rough K, Wright AA, et al.
Understanding treatment refusal among adults presenting for HIV-testing in Soweto, South Africa: a qualitative study.
AIDS Behav 2014; doi:10.1007/s10461-014-0920-y; Published Online First.
20. Ouattara E, Danel C, Moh R, Gabillard D, Peytavin G, Konan R, et al.
Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in west African adults with high CD4 counts.
J Int AIDS Soc 2013; 16:18059.
21. Jean K, Gabillard D, Moh R, Danel C, Fassassi R, Desgrées-du-LoÛ A, et al.
Effect of early antiretroviral therapy on sexual behaviors and HIV-1 transmission risk among adults with diverse heterosexual partnership statuses in Côte d’Ivoire.
J Infect Dis 2014; 209:431–440.
