Joseph Larmarange

Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa

Joseph LARMARANGE — 2023-07-20T11:00:49Z

Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa

Joseph Larmarange , Pamela Bachanas , Timothy Skalland , Laura Balzer , Collins Iwuji , Sian Floyd , Lisa Mills , Deenan Pillay , Diane Havlir , Moses Kamya , Helen Ayles , Kathleen Wirth , François Dabis , Richard Hayes , Maya Petersen

PLOS Global Public Health, 2023, 3 (7), pp.e0002157. ⟨10.1371/journal.pgph.0002157⟩

Article dans une revue

hal-04166971

Authors

Joseph Larmarange, Pamela Bachanas, Timothy Skalland, Laura B. Balzer, Collins Iwuji, Sian Floyd, Lisa A. Mills, Deenan Pillay, Diane Havlir, Moses R. Kamya, Helen Ayles, Kathleen Wirth, François Dabis, Richard Hayes, Maya Petersen, for the UT³C consortium

Abstract

Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV).

We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression–defined as plasma HIV RNA >500 or >400 copies/mL–among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation.

HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY.

Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression).

Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level.

Achieving the UNAIDS 90–90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa

Joseph LARMARANGE — 2022-12-18T12:26:51Z

Achieving the UNAIDS 90–90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa

K. Sabapathy , L. Balzer , Joseph Larmarange , L. Block , S. Floyd , C. Iwuji , K. Wirth , H. Ayles , S. Fidler , M. Kamya , M. Petersen , D. Havlir , F. Dabis , J. Moore , R. Hayes

BMC Public Health, 2022, 22 (1), pp.2333. ⟨10.1186/s12889-022-14713-5⟩

Article dans une revue

ird-03905396

Authors

K. Sabapathy, L. Balzer, J. Larmarange, L. Block, S. Floyd, C. Iwuji, K. Wirth, H. Ayles, S. Fidler, M. Kamya, M. Petersen, D. Havlir, F. Dabis, J. Moore & R. Hayes

Abstract

Background
Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012–2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90–90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90–90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90–90-90 targets.

Methods
Estimates were based predominantly on “process” data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field.

Results
The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin ( 3%) of the target.

Conclusions
All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings.

All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90–90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95–95-95 by 2030 and fast-track the end of the HIV epidemic.

Population-level Viremia Predicts HIV Incidence across the Universal Test and Treat Studies

Joseph LARMARANGE — 2020-03-19T11:06:07Z

Oral communication virtually presented at CROI 2020 the 9^th of March 2020

Authors

Maya Petersen, Joseph Larmarange, Kathleen Wirth, Timothy Skalland, Helen Ayles, Moses Kamya, Shahin Lockman, Collins Iwuji, François Dabis, Joseph Makhema, Diane Havlir, Sian Floyd, Richard Hayes for the UT3C Consortium

Abstract

Improved understanding of the extent to which increased population-level viral suppression will reduce HIV incidence is needed. Using data from four large Universal Test and Treat Trials, we evaluated the relationship between viremia and incidence and its consistency across epidemic contexts.

We analyzed data from 105 communities in the PopART (21 communities in South Africa and Zambia, 25,000 adults each), BCPP (30 communities in Botswana, 3,600 adults each), ANRS 12249 TasP (22 communities in South Africa, 1,300 adults each) and SEARCH (32 communities in Uganda and Kenya, 5,000 adults each) studies. Communities ranged from rural to urban and varied in the mobility of their populations and their sex ratio ( 30% to 50% male). HIV incidence was measured via repeat testing between 2012-2018. Population viremia – % of all adults (HIV+ or HIV-) with HIV viremia – was estimated at midpoint of follow-up based on HIV prevalence and non-suppression among HIV+, with adjustment for differences between the measurement cohort and underlying population. Community-level regression, adjusted for study, was used to quantify the association between HIV incidence and viremia and to evaluate cross-study heterogeneity.

HIV prevalence (measured in 257,929 total persons, PopART: 37,006; BCPP: 12,570; TasP: 20,978; SEARCH: 187,375), ranged from 2% to 40% by community. Non-suppression among HIV+ (measured in 39,928 persons, PopART: 6,233; BCPP: 2,318; TasP: 6,617; SEARCH: 16,209) ranged from 3% to 70%. HIV incidence (measured over 345,844 person-years, PopART: 39,702; BCPP: 8,551; TasP: 26,832; SEARCH: 270,759) ranged from 0.03 to 3.4 per 100PY. Population-level viremia was strongly associated with HIV incidence; pooling across studies, HIV incidence decreased by 0.07/100PY (95% CI: 0.05,0.10, p<0.001) for each 1% absolute decrease in viremia. Incidence was significantly associated with viremia in each study; however, both strength of the incidence-viremia relationship (slope) and projected incidence at 0% viremia (intercept) differed (Figure).

Lower population-level HIV viremia was associated with lower HIV incidence in all four Universal Test and Treat Studies, conducted in a wide range of epidemic contexts in sub-Saharan Africa. Differences in external infection rate (due to variation in community size, mobility, and sex ratio) may have contributed to heterogeneity between studies.

Reference

Petersen Maya, Larmarange Joseph, Wirth Kathleen E, Skalland Timothy, Ayles Helen, Kamya Moses, Lockman Shahin, Iwuji Collins, Dabis François, Makhema Joseph, Havlir Diane, Floyd Sian, Hayes Richard and UT3C Consortium (2020) “Population-level Viremia Predicts HIV Incidence across the Universal Test and Treat Studies” (communication orale), presented at the Conference on Retroviruses and Opportunitic Infections (CROI), Boston. http://www.croiconference.org/sessions/population-level-viremia-predicts-hiv-incidence-across-universal-test-treat-studies.

Impact des biais de trois Enquêtes Démographiques et de Santé africaines sur l'estimation de la prévalence nationale du VIH

Joseph LARMARANGE — 2008-10-14T17:00:00Z

Communication orale à la 15^e Conférence Internationale sur le Sida et les Infections sexuellement transmissibles en Afrique (CISMA - ICASA en anglais) du 3 au 7 décembre 2008 à Dakar.

Auteurs

J. Larmarange [1], R. Vallo [2], S. Yaro [3], P. Msellati [4], N. Méda [3], B. Ferry [1]

Abstract

Objectif

Depuis 2001, plusieurs enquêtes nationales en population générale avec dépistage du VIH, en particulier des Enquêtes Démographiques et de Santé (EDS), ont été menées en Afrique subsaharienne. Dans certains pays, leurs résultats étaient sensiblement différents de ceux de la surveillance sentinelle en cliniques prénatales. Les taux de non réponse (refus ou absence) des EDS ont souvent été cités pour expliquer ces différences. L'objectif de ce travail vise à estimer l'impact des différents biais de trois EDS (Burkina Faso 2003, Cameroun 2004 et Kenya 2003) sur la prévalence nationale du VIH mesurée.

Méthode

Nous avons eu recours à une modélisation mathématique pour estimer les individus infectés non observables du fait de la fenêtre sérologique des tests de dépistage. Des données de recensement et de l'UNHCR ont permis de prendre en compte les individus hors ménages ordinaires, dont les réfugiés en camps. L'ancienneté des bases de sondage utilisées a été compensée à partir de projections de population. Nous avons posé deux hypothèses simples concernant les ménages éligibles non enquêtés, considérant que leur prévalence était soit double soit moitié moindre. Enfin, la prévalence des individus éligibles mais non testés a pu être estimée à partir de modèles logistiques. Lorsque les données étaient faibles ou insuffisantes, nous avons maximisé l'amplitude des biais.

Résultats

Au Burkina Faso, la prévalence observée est de 1,77 % (IC 95 % : 1,49-2,11) tandis que la prévalence ajustée est de 1,86 % pour l'hypothèse haute et 1,82 % pour l'hypothèse basse. Elles sont respectivement de 5,44 % (5,00-5,91), 5,84 % et 5,43 % au Cameroun, 6,88 % (6,27-7,54), 7,16 % et 6,55 % au Kenya. Pour les trois EDS, la prévalence ajustée est située au sein de l'intervalle de confiance à 95 % de la prévalence observée, et même au sein de l'intervalle de confiance à 75 % (excepté l'hypothèse haute au Cameroun).

Conclusion

Les résultats des EDS constituent de bons indicateurs du niveau de la prévalence nationale du VIH parmi les adultes en population générale. L'impact des différentes sources de biais reste limité, inférieur aux erreurs d'échantillonnage. L'approche d'ONUSIDA consistant à estimer le niveau des épidémies à partir d'enquêtes en population générale s'avère pertinente.

[1] IRD – CEPED UMR 196 Paris Descartes INED IRD, Paris, France

[2] Université de Montpellier I – EA 4205, Montpellier, France

[3] Centre Muraz, Bobo-Dioulasso, Burkina Faso

[4] IRD – UMR 145, Marseille, France

Prévalences du VIH en Afrique : validité d'une mesure

Joseph LARMARANGE — 2007-10-01T13:37:36Z

Larmarange Joseph (2007). Prévalences du VIH en Afrique : validité d'une mesure, thèse pour l'obtention du grade de docteur en démographie, Université Paris Descartes (http://tel.archives-ouvertes.fr/tel-00320283/fr/), RIS, BibTeX.

Jury

– Benoît FERRY (IRD) - Directeur
– Yves CHARBIT (Université Paris Descartes) - Président
– Éva LELIÈVRE (INED) - Rapporteur
– Philippe MSELLATI (IRD) - Rapporteur
– Arnaud FONTANET (Institut Pasteur)
– Nicolas MÉDA (Centre Muraz - Burkina Faso)

Projet de recherche associé :

– Mesures et Ajustement des prévalences du VIH

Prévalences du VIH en Afrique : validité d'une mesure

Les prévalences nationales du VIH sont estimées, en Afrique subsaharienne, à partir de deux sources : la surveillance sentinelle des femmes enceintes et les enquêtes nationales en population générale (EDS). En plusieurs endroits, les résultats divergent, questionnant la validité de chaque approche. Quelles portée, limites et signification objective peuvent être accordées aux diverses observations, chacune appréhendant le réel sous un angle différent ?

Les EDS constituent un bon indicateur du niveau des épidémies à l'échelle national et régional, voir infrarégional grâce au recours à des techniques d'analyse spatiale en composantes d'échelles. Mais leur fréquence est inadaptée pour mesurer les évolutions à court terme. La surveillance sentinelle, estimateur local des ordres de grandeur, peut être un indicateur de tendances sous certaines conditions. Cependant, si la situation actuelle commence à être mieux connue, une mesure réelle des dynamiques est encore hors de notre portée.

Mots-Clés

VIH/SIDA, Afrique subsaharienne, prévalence, validité épistémologique, EDS (Enquêtes Démographiques et de Santé), surveillance sentinelle, interpolation spatiale, épidémiologie.

HIV prevalence in Africa : validity of a measurement

HIV national prevalence is estimated, in sub-Saharan Africa, from two main data sources : sentinel surveillance of pregnant women and national population-based surveys (DHS). In several countries, results differ, questioning each of those approaches' efficiency. What range, limitations and objective significance can be granted to the diverse observations, each apprehending the real from a different point of view ?

DHS constitute a good indicator of prevalence levels at a national or a regional scale. Intraregional variations can be reproduced by using spatial analysis techniques. But DHS frequencies are inaccurate to measure short-term evolution. Sentinel surveillance, local estimator of magnitude of epidemics, can be a tendency indicator under certain conditions. However, if the present situation is only just starting to be better-known, a real measurement of HIV dynamics is still out of our reach.

Key Words

HIV/AIDS, sub-Saharan Africa, prevalence, epistemological validity, DHS (Demographic and Health Surveys, sentinel surveillance, spatial interpolation, epidemiology.

Estimating effect of non response on HIV prevalence estimates with DHS data

Joseph LARMARANGE — 2007-05-03T09:28:22Z

8th AIDS Impact conference, Marseille, 1-4 juillet 2007

Authors

Joseph LARMARANGE, Roselyne VALLO, Seydou YARO, Philippe MSELLATI, Nicolas MÉDA, Benoît FERRY.

Abstract

Aim

In most countries in Sub-Saharan Africa, Demographic and Health Surveys (DHS) with HIV testing became the only measure of HIV prevalence in general population. Significant non response rate were often cited to explain differences between DHS results and estimations from sentinel surveillance in antenatal clinics. The objective of this presentation consists to predict with multivariate models the prevalence of non tested persons in order to estimate the effect of non response on national estimates.

Method / Issue

We used data from 9 DHS surveys (Burkina Faso 2003, Cameroon 2004, Ethiopia 2005, Ghana 2003, Kenya 2003, Lesotho 2004, Malawi 2004, Senegal 2005 and Tanzanie 2003) where HIV results could be linked with data from household and individual questionnaires. Logistic regression were calculated for each country, separately for men and women 15-49 years old, with common predictor variables : region, place of residence, age group, education, wealth index, marital status, work status, having radio or television, age at first sexual intercourse, recent sexual activities, using condom at last sexual intercourse, number of partners in last 12 months, smoking, STI in last 12 months, female and male circumcision and willing to care for relative with AIDS. For each group, adjusted prevalence was calculated by using observed prevalence for tested people and estimated prevalence for non tested people.

Results / Comments

The non response rates in these 9 studies vary from 7.9% to 34.2%. Estimated prevalence of non tested persons is usually higher than observed prevalence of tested persons : in 15 groups on 18, the ratio exceeds 1 (it vary from 0.820 to 2.424). Nevertheless, ratios of adjusted prevalence to observed prevalence remain relatively small (from 0.956 to 1.251). Except for men in Lesotho and women in Malawi, differences between adjusted and observed prevalence is less than 0.5 points. In both cases, number of tested persons was small (less than 3'000). No relation was found between non response rate and ratio of non tested to tested or ratio of adjusted prevalence to observed prevalence. Nevertheless, highest ratio of adjusted prevalence to observed prevalence were found for groups with smallest prevalence (<3%). But this effect is probably a consequence of a small statistical power.

Discussion

If differences between adjusted and observed prevalence are more important than in a precedent survey conducted by Mishra et al. in 2006 on 5 DHS, the overall effect of non response bias on national HIV estimates tend to be small. Adjustments need to be interpreted with caution due to the limited information available to predict the prevalence of non tested people, in particular for people who did not answer the individual questionnaire and for whom only household questionnaire data were used.