Joseph Larmarange

Décrire les épidémies, Comprendre les populations : une démographie du VIH en Afrique subsaharienne

Joseph LARMARANGE — 2022-10-14T06:38:12Z

Habilitation à Diriger des Recherches soutenue le 12 octobre 2012 par Joseph Larmarange à l'Université Paris Cité.
Décrire les épidémies, Comprendre les populations : une démographie du VIH en Afrique subsaharienne
Joseph Larmarange Démographie. Université Paris Cité, 2022 HDR tel-03814024

- Publications / Afrique subsaharienne, ATLAS, CAP-CoV-Soignants-BF, DOD-CI (ANRS 12287 / 12323), ELIHoS (ANRS 12139), PrEP CI (ANRS 12361), Prévalences du VIH (ANRS 12114), prevR, PRINCESSE, TasP (ANRS 12249), Afrique du Sud, Burkina Faso, Côte d'Ivoire, Mali, Sénégal, Accès aux soins, Analyse de séquences, Approches biographiques, Approches communautaires, Autotests VIH, Cartographie, Cascade des soins, Comparaison de cohortes, Comportements sexuels, Démographie, Dépistage, EDS (Enquêtes Démographiques et de Santé), Enquêtes par téléphone, Enseignement académique, Lien vers les soins, Épidémiologie, Essais cliniques, Estimateurs à noyau (kernel density estimation), Femmes enceintes, Financement des programmes, Hépatites virales, Homo / Bisexualités, Identités sexuelles, Incidence du VIH, Interpolation spatiale, IST (Infections Sexuellement Transmissibles), Itinéraires thérapeutiques, Masculinités, Ménages, Mesure d'impact, Mesure des indicateurs, Méthodologie, Migrations, Observatoire de population, Partenaires sexuel(le)s, PrEP, Prévalence du VIH, Prévention, Prise en charge, Recherche interventionnelle, Recherche participative/communautaire, Recrutement « boules de neige », Représentations / Perceptions, Représentativité et Biais, Santé publique, Santé sexuelle, Structure des populations, Structures de santé, Surveillance sentinelle, Téléphones mobiles, Temporalités, Traitement antirétroviral (ARV), Travail du sexe, Treatment as Prevention (TasP), Universal Test & Treat (UTT), Usageres de drogue, VIH / SIDA

A community-based healthcare package combining testing and prevention tools, including pre-exposure prophylaxis (PrEP), immediate HIV treatment, management of hepatitis B virus, and sexual and reproductive health (SRH), targeting female sex workers (FSWs) in Côte d'Ivoire: the ANRS 12381 PRINCESSE project

Joseph LARMARANGE — 2021-12-06T09:50:35Z

Protocol paper of the ANRS 12381 PRINCESSE project.

A community-based healthcare package combining testing and prevention tools, including pre-exposure prophylaxis (PrEP), immediate HIV treatment, management of hepatitis B virus, and sexual and reproductive health (SRH), targeting female sex workers (FSWs) in Côte d'Ivoire: the ANRS 12381 PRINCESSE project

Valentine Becquet , Marcellin Nouaman , Mélanie Plazy , Aline Agoua , Clémence Zébago , Hervé Dao , Alice Montoyo , Aude Jary , Patrick A. Coffie , Serge Eholié , Joseph Larmarange

BMC Public Health, 2021, 21 (1), pp.2214. ⟨10.1186/s12889-021-12235-0⟩

Article dans une revue

hal-03467822

Authors

Valentine Becquet, Marcellin Nouaman, Mélanie Plazy, Aline Agoua, Clémence Zébago, Hervé Dao, Alice Montoyo, Aude Jary, Patrick A. Coffie, Serge Eholié, Joseph Larmarange & and the ANRS 12381 PRINCESSE team

Abstract

Background

Pre-exposure prophylaxis (PrEP) is recommended by the WHO for HIV prevention among female sex workers (FSWs). A study conducted in 2016–2017 in Côte d'Ivoire showed that if PrEP is acceptable, FSWs also have many uncovered sexual health needs. Based on this evidence, the ANRS 12381 PRINCESSE project was developed in collaboration with a community-based organization. The main objective is to develop, document, and analyze a comprehensive sexual and reproductive healthcare package among FSWs in Côte d'Ivoire.

Methods

PRINCESSE is an open, single-arm interventional cohort of 500 FSWs in San Pedro (Côte d'Ivoire) and its surroundings. Recruitment started on November 26^th, 2019 and is ongoing; the cohort is planned to last at least 30 months. The healthcare package (including HIV, hepatitis B, and sexually transmitted infection management, pregnancy screening, and contraception) is available both at mobile clinics organized for a quarterly follow-up (10 intervention sites, each site being visited every two weeks) and at a fixed clinic.

Four waves of data collection were implemented: (i) clinical and safety data; (ii) socio-behavioral questionnaires; (iii) biological data; and (iv) in-depth interviews with female participants. Four additional waves of data collection are scheduled outside the cohort itself: (i) the medical and activity records of Aprosam for the PRINCESSE participants; (ii) the medical records of HIV+ FSW patients not participating in the PRINCESSE cohort, and routinely examined by Aprosam; (iii) in-depth interviews with key informants in the FSW community; and (iv) in-depth interviews with PRINCESSE follow-up actors.

Discussion

The PRINCESSE project is one of the first interventions offering HIV oral PrEP as part of a more global sexual healthcare package targeting both HIV- and HIV+ women. Second, STIs and viral hepatitis B care were offered to all participants, regardless of their willingness to use PrEP. Another innovation is the implementation of mobile clinics for chronic/quarterly care. In terms of research, PRINCESSE is a comprehensive, interdisciplinary project combining clinical, biological, epidemiological, and social specific objectives and outcomes to document the operational challenges of a multidisease program in real-life conditions.

Trial registration

The PRINCESSE project was registered on the Clinicaltrial.gov website (NCT03985085) on June 13, 2019.

Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial

Joseph LARMARANGE — 2018-03-19T17:08:52Z

Authors

Collins C Iwuji, Joanna Orne-Gliemann, Joseph Larmarange, Eric Balestre, Rodolphe Thiebaut, Frank Tanser, Nonhlanhla Okesola, Thembisa Makowa, Jaco Dreyer, Kobus Herbst, Nuala McGrath, Till Bärnighausen, Sylvie Boyer, Tulio De Oliveira, Claire Rekacewicz, Brigitte Bazin, Marie-Louise Newell, Deenan Pillay, François Dabis, for the ANRS 12249 TasP Study Group

Abstract

Background

Universal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa.

Methods

We did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and <500 cells per μL from January, 2015; control). Participants and investigators were not masked to treatment allocation. We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up. This study is registered with ClinicalTrials.gov, number NCT01509508, and the South African National Clinical Trials Register, number DOH-27-0512-3974.

Findings

Between March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84–2·39) in the intervention group and 2·27 per 100 person-years (2·00–2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87–1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83).

Interpretation

The absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence.

Funding

ANRS, GiZ, and 3ie.

Reference

Iwuji Collins C, Orne-Gliemann Joanna, Larmarange Joseph, Balestre Eric, Thiebaut Rodolphe, Tanser Frank, Okesola Nonhlanhla, Makowa Thembisa, Dreyer Jaco, Herbst Kobus, McGrath Nuala, Bärnighausen Till, Boyer Sylvie, De Oliveira Tulio, Rekacewicz Claire, Bazin Brigitte, Newell Marie-Louise, Pillay Deenan and Dabis François (2018) “Universal test and treat and the HIV epidemic in rural South Africa: a phase 4, open-label, community cluster randomised trial”, The Lancet HIV, 5 (3) (March 1), p. e116-e125. DOI : 10.1016/S2352-3018(17)30205-9. http://www.sciencedirect.com/science/article/pii/S2352301817302059.

Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

Joseph LARMARANGE — 2016-08-17T15:20:49Z

Authors

Collins C. Iwuji, Joanna Orne-Gliemann, Joseph Larmarange, Nonhlanhla Okesola, Frank Tanser, Rodolphe Thiebaut, Claire Rekacewicz, Marie-Louise Newell, Francois Dabis for the ANRS 12249 TasP trial group

Abstract

Background

The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.

Methods and Findings

Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded.

In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded.

Conclusions

Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

Trial registration

ClinicalTrials.gov NCT01509508

Reference

Iwuji Collins C., Orne-Gliemann Joanna, Larmarange Joseph, Okesola Nonhlanhla, Tanser Frank, Thiebaut Rodolphe, Rekacewicz Claire, Newell Marie-Louise, Dabis Francois and Group ANRS 12249 TasP trial (2016) “Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial”, PLOS Med, 13 (8) (August 9), p. e1002107. DOI : 10.1371/journal.pmed.1002107. http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002107.

The impact of universal test and treat on HIV incidence in a rural South African population: ANRS 12249 TasP trial, 2012-2016

Joseph LARMARANGE — 2016-08-17T14:54:58Z

The main results of the ANRS 12249 Treatment as Prevention trail were presented at the 21^st International AIDS Conference (AIDS 2016) in Durban in July 2016.

Authors

C. Iwuji, J. Orne-Gliemann, E. Balestre, J. Larmarange, R. Thiebaut, F. Tanser, N. Okesola, T. Makowa, J. Dreyer, K. Herbst, N. Mc Grath, T. Barnighausen, S. Boyer, T. De Oliveira, C. Rekacewicz, B. Bazin, M.-L. Newell, D. Pillay, F. Dabis, for the ANRS 12249 TasP Study Group

Abstract

Background: The population impact of universal test and treat (UTT) on HIV transmission has not yet been evaluated.

Methods: A cluster-randomized trial was implemented in 2x11 rural communities in KwaZulu-Natal, South Africa. All residents ≥16 years were offered rapid HIV testing and provided dried blood spots (DBS) during 6-monthly home-based survey rounds. HIV-positive participants were referred to cluster-based trial clinics to receive ART regardless of CD4 count (intervention arm) or according to national guidelines (control arm). Standard of care ART was also available in the Department of Health clinics. HIV incidence was estimated on repeat DBS using cluster-adjusted Poisson regression.

Results: Between 03/2012 and 04/2016, 13,239 and 14,916 individuals (63% women, median age 30 years) were registered in the intervention and control arms. Contact frequency per round among registered individuals ranged from 64% to 83%, HIV ascertainment from 74% to 85%. Baseline HIV prevalence was 29.4%(95%CI 28.8-30.0), with 7,578 individuals identified as HIV-positive. 1,513(36%) of 4,172 HIV-positive individuals not previously in care linked to trial clinics within 6 months of referral. ART initiation in trial clinics at 3 months was 90.9%(576/634) and 52.3%(332/635) in the intervention and control arms; viral suppression (< 400 copies/mL) 12 months after ART initiation was 94.9%(300/316) and 94.2%(194/206), respectively. Overall ART coverage at entry was 31% and 36% in the intervention and control arms, reaching 41% in both arms by closing date. Repeat DBS tests were available for 13,693 individuals HIV-negative at baseline, yielding 461 seroconversions in 20,833 person-years (PY). HIV incidence was 2.16 per 100 PY (1.88-2.45) in the intervention arm and 2.26 (1.98-2.54) in the control arm (adjusted relative risk: 0.95 [0.82-1.10]). Severe adverse events rates were 3.4%(45/1,323) and 3.5%(57/1,604) in the intervention and control arms. Follow-up will be completed by 06/2016.

Conclusions: Our trial shows high acceptance of home-based HIV testing and high levels of viral suppression among individuals on ART. However overall linkage to care remains poor. No reduction in HIV incidence was demonstrated. Several factors are being investigated, including determinants of poor linkage, change in national ART guidelines, migration and geography of sexual networks.

(Funded by ANRS, GiZ and 3ie; Clinical Trials registration NCT00332878)

Medias

Reference

Iwuji Collins, Orne-Gliemann Joanna, Balestre Eric, Larmarange Joseph, Thiébaut Rodolphe, Tanser Frank, Okesola Nonhlanhla, Makowa Thembisa, Dreyer Jaco, Herbst Kobus, McGrath Nuala, Bärnighausen Till, Boyer Sylvie, de Oliveira Tulio, Rekacewicz Claire, Bazin Brigitte, Newell Marie-Louise, Pillay Deenan, Dabis François and ANRS 12249 TasP Study Group (2016) “The impact of universal test and treat on HIV incidence in a rural South African population: ANRS 12249 TasP trial, 2012-2016” (communication orale n°FRAC0105LB), presented at the 21st International AIDS Conference (AIDS 2016), Durban. http://programme.aids2016.org/Abstract/Abstract/10537.

Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal

Joseph LARMARANGE — 2015-03-21T12:21:37Z

Authors

Joanna Orne-Gliemann†, Joseph Larmarange†, Sylvie Boyer, Collins Iwuji, Nuala McGrath, Till Bärnighausen, Thembelile Zuma, Rosemary Dray-Spira, Bruno Spire, Tamsen Rochat, France Lert, John Imrie and for the ANRS 12249 TasP Group

† Equal contributors

Abstract

Background

The Universal HIV Test and Treat (UTT) strategy represents a challenge for science, but is also a challenge for individuals and societies. Are repeated offers of provider-initiated HIV testing and immediate antiretroviral therapy (ART) socially-acceptable and can these become normalized over time? Can UTT be implemented without potentially adding to individual and community stigma, or threatening individual rights? What are the social, cultural and economic implications of UTT for households and communities? And can UTT be implemented within capacity constraints and other threats to the overall provision of HIV services? The answers to these research questions will be critical for routine implementation of UTT strategies.

Methods/design

A social science research programme is nested within the ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomised trial in rural South Africa. The programme aims to inform understanding of the (i) social, economic and environmental factors affecting uptake of services at each step of the continuum of HIV prevention, treatment and care and (ii) the causal impacts of the TasP intervention package on social and economic factors at the individual, household, community and health system level. We describe a multidisciplinary, multi-level, mixed-method research protocol that includes individual, household, community and clinic surveys, and combines quantitative and qualitative methods.

Discussion

The UTT strategy is changing the overall approach to HIV prevention, treatment and care, and substantial social consequences may be anticipated, such as changes in social representations of HIV transmission, prevention, HIV testing and ART use, as well as changes in individual perceptions and behaviours in terms of uptake and frequency of HIV testing and ART initiation at high CD4. Triangulation of social science studies within the ANRS 12249 TasP trial will provide comprehensive insights into the acceptability and feasibility of the TasP intervention package at individual, community, patient and health system level, to complement the trial's clinical and epidemiological outcomes. It will also increase understanding of the causal impacts of UTT on social and economic outcomes, which will be critical for the long-term sustainability and routine UTT implementation.

Trial registration

Clinicaltrials.gov: NCT01509508 webcite; South African Trial Register: DOH-27-0512-3974.

Keywords

HIV infections; HIV testing; Community; HIV care; Antiretroviral treatment; Social; Behaviour; Cost; South Africa

Reference

Orne-Gliemann Joanna, Larmarange Joseph, Boyer Sylvie, Iwuji Collins, McGrath Nuala, Bärnighausen Till, Zuma Thembelihle, Dray-Spira Rosemary, Spire Bruno, Rochat Tamsen, Lert France, Imrie John and ANRS 12249 TasP Study Group (2015) “Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal”, BMC Public Health, 15 (1) (March 1), p. 209. DOI : 10.1186/s12889-015-1344-y. http://www.biomedcentral.com/1471-2458/15/209/abstract.

Dépister & Traiter : entre bénéfice individuel et bénéfice collectif

Joseph LARMARANGE — 2014-09-06T12:08:37Z

Communication présentée le 8 septembre 2014 dans le cadre d'une journée d'étude Les essais cliniques, quelles preuves pour quels résultats ? organisée par Charlotte Brives, Frédéric Le Marcis et Nicolas Lechopier (S2HEP – ENS-Lyon-Ifé).

Résumé

Le traitement antirétroviral (ARV) comme moyen de prévention de la transmission du VIH constitue actuellement l'une des questions scientifiques majeures dans le domaine de la lutte contre le Sida. Plusieurs grands essais, dont TasP (ANRS 12249) et PopART, sont en cours pour tester l'efficacité d'une approche dite « dépister et traiter », dans des contextes hyper-endémiques. Il s'agit d'essais menés en population générale, randomisés en grappes. À la différence des essais cliniques « classiques », la sélection aléatoire n'est pas effectuée sur des individus mais sur des zones géographiques ou grappes, avec l'hypothèse que ces grappes permettent de capter des réseaux sexuels endogènes. Une autre particularité de ce type d'essai est de mettre en place une intervention auprès de certains individus (mise sous ARV immédiate, quelle que soit la situation clinique ou biologique, des personnes infectées par le VIH) pour en mesurer l'effet sur d'autres individus (les personnes non infectées au début de l'essai), sous l'hypothèse d'un bénéfice collectif du traitement (la baisse des nouvelles infections). Or, un tel bénéfice collectif ne peut se justifier à lui seul s'il n'y a pas également un bénéfice individuel, bénéfice non encore prouvé au-dessus de 500 CD4, les essais TEMPRANO et START n'ayant pas encore publié leurs résultats. De plus, ce bénéfice collectif est fortement dépendant du taux de participation dans l'étude. Par ailleurs, dû l'évolution rapide des recommandations internationales (l'OMS préconisant maintenant une mise sous ARV à 500 CD4), il y a un risque que ces essais ne puissent conclure du fait de la dilution de l'effet entre bras interventionnel et bras témoin. Quelles seraient alors les recommandations à tirer de ces essais ? Enfin, au-delà des essais eux-mêmes, les stratégies « dépister et traiter » posent plusieurs questions éthiques, notamment autour du « déplacement » de la responsabilité de la transmission vers la personne ne prenant pas son traitement ou encore de la fin de l'exceptionnalité du dépistage du VIH malgré le fait que cette pathologie reste fortement stigmatisante.

Référence

Larmarange Joseph (2014) “Dépister & Traiter : entre bénéfice inspaniduel et bénéfice collectif” (communication orale), presented at the Journée d'étude de l'ENS "Les essais cliniques, quelles preuves pour quels résultats ?", Lyon. http://triangle.ens-lyon.fr/spip.php?article4294.