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The impact of population dynamics on the population HIV care cascade: results from the ANRS 12249 Treatment as Prevention trial in rural KwaZulu-Natal (South Africa).

ABSTRACT: INTRODUCTION:The universal test and treat strategy (UTT) was developed to maximize the proportion of all HIV-positive individuals on antiretroviral treatment (ART) and virally suppressed, assuming that it will lead to a reduction in HIV incidence at the population level. The evolution over time of the cross-sectional HIV care cascade is determined by individual longitudinal trajectories through the HIV care continuum and underlying population dynamics. The purpose of this paper is to quantify the contribution of each component of population change (in- and out-migration, HIV seroconversion, ageing into the cohort and definitive exit such as death) on the HIV care cascade in the context of the ANRS 12249 Treatment as Prevention (TasP) cluster-randomized trial, investigating UTT in rural KwaZulu-Natal, South Africa, between 2012 and 2016. METHODS:HIV test results and information on clinic visits, ART prescriptions, viral load and CD4 count, migration and deaths were used to calculate residency status, HIV status and HIV care status for each individual on a daily basis. Position within the HIV care continuum was considered as a score ranging from 0 (undiagnosed) to 4 (virally suppressed). We compared the cascade score of each individual joining or leaving the population of resident adults living with HIV with the average score of their cluster at the time of entry or exit. Then, we computed the contribution of each entry or exit on the average cascade score and their annualized total contribution, by component of change. RESULTS:While the average cascade score increased over time in all clusters, that increase was constrained by population dynamics. Permanent exits and ageing into the people living with HIV cohort had a marginal effect. Both in-migrants and out-migrants were less likely to be retained at each step of the HIV care continuum. However, their overall impact on the cross-sectional cascade was limited as the effect of in- and out-migration balanced each other. The contribution of HIV seroconversions was negative in all clusters. CONCLUSIONS:In a context of high HIV incidence, the continuous flow of newly infected individuals slows down the efforts to increase ART coverage and population viral suppression, ultimately attenuating any population-level impact on HIV incidence. CLINICAL TRIAL NUMBER:NCT01509508 (clinicalTrials.gov)/DOH-27-0512-3974 (South African National Clinical Trials Register).

SUBMITTER: Larmarange J

PROVIDER: S-EPMC6053480 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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The impact of population dynamics on the population HIV care cascade: results from the ANRS 12249 Treatment as Prevention trial in rural KwaZulu-Natal (South Africa).

Larmarange Joseph J Diallo Mamadou Hassimiou MH McGrath Nuala N Iwuji Collins C Plazy Mélanie M Thiébaut Rodolphe R Tanser Frank F Bärnighausen Till T Pillay Deenan D Dabis François F Orne-Gliemann Joanna J

Journal of the International AIDS Society 20180701

<h4>Introduction</h4>The universal test and treat strategy (UTT) was developed to maximize the proportion of all HIV-positive individuals on antiretroviral treatment (ART) and virally suppressed, assuming that it will lead to a reduction in HIV incidence at the population level. The evolution over time of the cross-sectional HIV care cascade is determined by individual longitudinal trajectories through the HIV care continuum and underlying population dynamics. The purpose of this paper is to qua ...[more]

PMID: 30027600

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Project description:BackgroundTreatment and control of hypertension are associated with a substantial reduction in adverse cardiovascular disease outcomes. Although South Africa aims to reduce the burden of cardiovascular diseases, there is limited evidence on the hypertension care cascade (HCC) performance in rural areas where stroke and hypertension are high. This study estimated HCC performance and identified predictors of hypertension screening among adults in the Ingwavuma community of KwaZulu-Natal, South Africa.MethodsThis was a cross-sectional study. Data were collected using the WHO STEPwise approach to surveillance (STEPS) questionnaire from 400 adult participants, excluding pregnant women and those with physical or cognitive impairments. Three hundred and ninety-three participants had complete data, and 131 had high blood pressure. We calculated progression rates for screening, diagnosis, treatment and control of hypertension from the sub-sample of participants with high blood pressure and assessed the bivariate association between HCC stages and participant characteristics and their effect sizes. We used binary and multivariable logistic regression to identify predictors of hypertension screening.ResultsEighty-eight per cent of participants reported prior screening for hypertension. However, only 53.5% of patients under pharmacological treatment for hypertension had controlled blood pressure. In bivariate regression, employed participants were 80.3% (COR = 0.197, 95% CI [0.042-0.921]) more likely to be screened. In multivariable regression, the likelihood of hypertension screening was 82.4% (AOR = 0.176, 95% CI [0.047-0.655]) lower among participants in a cohabiting union than single participants. Similarly, employed participants were 87.4% (AOR = 0.129, 95% CI [0.017-0.952]) less likely to be screened than their unemployed counterparts.ConclusionsThe considerable attrition from the HCC across socio-demographic categories indicates a need for community-wide interventions. Empowering health care workers for community-based health promotion and hypertension management through point-of-care diagnostic tools could improve HCC performance. Efforts to improve the HCC should also focus on social determinants of health, notably gender and formal educational attainment.

Project description:ObjectivesResearch on migration and HIV has largely focused on male migration, often failing to measure HIV risks associated with migration for women. We aimed to establish whether associations between migration and HIV infection differ for women and men, and identify possible mechanisms by which women's migration contributes to their high infection risk.DesignData on socio-demographic characteristics, patterns of migration, sexual behavior and HIV infection status were obtained for a population of 11,677 women aged 15-49 and men aged 15-54, resident members of households within a demographic surveillance area participating in HIV surveillance in 2003-04.MethodsLogistic regression was conducted to examine whether sex and migration were independently associated with HIV infection in three additive effects models, using measures of recent migration, household presence and migration frequency. Multiplicative effects models were fitted to explore whether the risk of HIV associated with migration differed for males and females. Further modeling and simulations explored whether composition or behavioral differences accounted for observed associations.ResultsRelative to non-migrant males, non-migrant females had higher odds of being HIV-positive (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [1.49-1.99]), but odds were higher for female migrants (aOR = 2.55 [2.07-3.13]). Female migrants also had higher odds of infection relative to female non-migrants (aOR = 1.48 [1.23-1.77]). The association between number of sexual partners over the lifetime and HIV infection was modified by both sex and migrant status: For male non-migrants, each additional partner was associated with 3% higher odds of HIV infection (aOR = 1.03 [1.02-1.05]); for male migrants the association between number of partners and HIV infection was non-significant. Each additional partner increased odds of HIV infection by 22% for female non-migrants (aOR = 1.22 [1.12-1.32]) and 46% for female migrants (aOR = 1.46 [1.25-1.69]).ConclusionsHigher risk sexual behavior in the context of migration increased women's likelihood of HIV infection.

Project description:INTRODUCTION:High levels of HIV seroconcordance at the population level reduce the potential for effective HIV transmission. However, the level of HIV seroconcordance is largely unknown among heterosexual couples in sub-Saharan Africa. We aimed to quantify the population level HIV seroconcordance in stable heterosexual couples in rural South Africa. METHODS:We followed adults (≥15 years old) using a population-based, longitudinal and open surveillance system in KwaZulu-Natal, South Africa, from 2003 to 2016. Sexual partnerships and HIV status were confirmed via household surveys and annual HIV surveillance. We calculated the proportions of HIV seroconcordance and serodiscordance in stable sexual partnerships and compared them to the expected proportions under the assumption of random mixing using individual-based microsimulation models. Among unpartnered individuals, we estimated the incidence rates and hazard of sexual partnership formation with HIV-positive or HIV-negative partners by participants' own time-varying HIV status. Competing risks survival regressions were fitted adjusting for sociodemographic and clinical factors. We also calculated Newman's assortativity coefficients. RESULTS:A total of 18,341 HIV-negative and 11,361 HIV-positive individuals contributed 154,469 person-years (PY) of follow-up. Overall, 28% of the participants were in stable sexual partnerships. Of the 677 newly formed stable sexual partnerships, 7.7% (95% CI: 5.8 to 10.0) were HIV-positive seroconcordant (i.e. both individuals in the partnership were HIV-positive), which was three times higher than the expected proportion (2.3%) in microsimulation models based on random mixing. The incidence rates of sexual partnership formation were 0.54/1000PY with HIV-positive, 1.12/1000PY with HIV-negative and 2.65/1000PY with unknown serostatus partners. HIV-positive individuals had 2.39 (95% CI: 1.43 to 3.99) times higher hazard of forming a sexual partnership with an HIV-positive partner than did HIV-negative individuals after adjusting for age, opposite-sex HIV prevalence (by 5-years age groups), HIV prevalence in the surrounding community, ART coverage and other sociodemographic factors. Similarly, forming a sexual partnership with an HIV-negative partner was 1.47 (95% CI: 1.01 to 2.14) times higher in HIV-negative individuals in the adjusted model. Newman's coefficient also showed that assortativity by participant and partner HIV status was moderate (r = 0.35). CONCLUSIONS:A high degree of population level HIV seroconcordance (both positive and negative) was observed at the time of forming new sexual partnerships. Understanding factors driving these patterns may help the development of strategies to bring the HIV epidemic under control.

Project description:BackgroundThe 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 findingsBetween 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.ConclusionsHome-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 registrationClinicalTrials.gov NCT01509508.

Project description:Men's poorer engagement with healthcare generally and HIV care specifically, compared to women, is well-described. Within the HIV public health domain, interest is growing in universal test and treat (UTT) strategies. UTT strategies refer to the expansion of antiretroviral therapy (ART) in order to reduce onward transmission and incidence of HIV in a population, through a "treatment as prevention" (TasP). This paper focuses on how masculinity influences engagement with HIV care in the context of an on-going TasP trial. Data were collected in January-November 2013 using 20 in-depth interviews, 10 of them repeated thrice, and 4 focus group discussions, each repeated four times. Analysis combined inductive and deductive approaches for coding and the review and consolidation of emerging themes. The accounts detailed men's unwillingness to engage with HIV testing and care, seemingly tied to their pursuit of valued masculinity constructs such as having strength and control, being sexually competent, and earning income. Articulated through fears regarding getting an HIV-positive diagnosis, observations that men preferred traditional medicine and that primary health centres were not welcoming to men, descriptions that men used lay measures to ascertain HIV status, and insinuations by men that they were removed from HIV risk, the indisposition to HIV care contrasted markedly with an apparent readiness to test among women. Gendered tensions thus emerged which were amplified in the context where valued masculinity representations were constantly threatened. Amid the tensions, men struggled with disclosing their HIV status, and used various strategies to avoid or postpone disclosing, or disclose indirectly, while women's ability to access care readily, use condoms, or communicate about HIV appeared similarly curtailed. UTT and TasP promotion should heed and incorporate into policy and health service delivery models the intrapersonal tensions, and the conflict, and poor and indirect communication at the micro-relational levels of couples and families.

Project description:BackgroundTimely linkage to care and ART initiation is critical to decrease the risks of HIV-related morbidity, mortality and HIV transmission, but is often challenging. We report on the implementation and effectiveness of a linkage-to-care intervention in rural KwaZulu-Natal, South Africa.MethodsIn the ANRS 12249 TasP trial on Universal Testing and Treatment (UTT) implemented between 2012-2016, resident individuals ≥16 years were offered home-based HIV testing every six months. Those ascertained to be HIV-positive were referred to trial clinics. Starting May 2013, a linkage-to-care intervention was implemented in both trial arms, consisting of tracking through phone calls and/or home visits to "re-refer" people who had not linked to care to trial clinics within three months of the first home-based referral. Fidelity in implementing the planned intervention was described using Kaplan-Meier estimation to compute conditional probabilities of being tracked and of being re-referred by the linkage-to-care team. Effect of the intervention on time to linkage-to-care was analysed using a Cox regression model censored for death, migration, and end of data follow-up.ResultsAmong the 2,837 individuals (73.7% female) included in the analysis, 904 (32%) were tracked at least once, and 573 of them (63.4%) were re-referred. Probabilities of being re-referred was 17% within six months of first referral and 31% within twelve months. Compared to individuals not re-referred by the intervention, linkage-to-care was significantly higher among those with at least one re-referral through phone call (adjusted hazard ratio [aHR] = 1.82; 95% confidence interval [95% CI] = 1.47-2.25), and among those with re-referral through both phone call and home visit (aHR = 3.94; 95% CI = 2.07-7.48).ConclusionsPhone calls and home visits following HIV testing were challenging to implement, but appeared effective in improving linkage-to-care amongst those receiving the intervention. Such patient-centred strategies should be part of UTT programs to achieve the UNAIDS 95-95-95 targets.

Project description:IntroductionThe universal test-and-treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa.MethodsThe TasP cluster-randomized trial (2012 to 2016) implemented six-monthly repeat home-based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 × 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level.Results8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited.ConclusionsPVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART-initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90-90-90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context-specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH-27-0512-3974 (South African National Clinical Trials Register).

Project description:BACKGROUND:Standard approaches to estimation of losses in the HIV cascade of care are typically cross-sectional and do not include the population stages before linkage to clinical care. We used indiviual-level longitudinal cascade data, transition by transition, including population stages, both to identify the health-system losses in the cascade and to show the differences in inference between standard methods and the longitudinal approach. METHODS:We used non-parametric survival analysis to estimate a longitudinal HIV care cascade for a large population of people with HIV residing in rural KwaZulu-Natal, South Africa. We linked data from a longitudinal population health surveillance (which is maintained by the Africa Health Research Institute) with patient records from the local public-sector HIV treatment programme (contained in an electronic clinical HIV treatment and care database, ARTemis). We followed up all people who had been newly detected as having HIV between Jan 1, 2006, and Dec 31, 2011, across six cascade stages: three population stages (first positive HIV test, HIV status knowledge, and linkage to care) and three clinical stages (eligibility for antiretroviral therapy [ART], initiation of ART, and therapeutic response). We compared our estimates to cross-sectional cascades in the same population. We estimated the cumulative incidence of reaching a particular cascade stage at a specific time with Kaplan-Meier survival analysis. FINDINGS:Our population consisted of 5205 individuals with HIV who were followed up for 24?031 person-years. We recorded 598 deaths. 4539 individuals gained knowledge of their positive HIV status, 2818 were linked to care, 2151 became eligible for ART, 1839 began ART, and 1456 had successful responses to therapy. We used Kaplan-Meier survival analysis to adjust for censorship due to the end of data collection, and found that 8 years after testing positive in the population health surveillance, 16% had died. Among living patients, 82% knew their HIV status, 45% were linked to care, 39% were eligible for ART, 35% initiated ART, and 33% had reached therapeutic response. Median times to transition for these cascade stages were 52 months, 52 months, 20 months, 3 months, and 9 months, respectively. Compared with the population stages in the cascade, the transitions across the clinical stages were fast. Over calendar time, rates of linkage to care have decreased and patients presenting for the first time for care were, on average, healthier. INTERPRETATION:HIV programmes should focus on linkage to care as the most important bottleneck in the cascade. Cascade estimation should be longitudinal rather than cross-sectional and start with the population stages preceding clinical care. FUNDING:Wellcome Trust, PEPFAR.

Dataset Information

The impact of population dynamics on the population HIV care cascade: results from the ANRS 12249 Treatment as Prevention trial in rural KwaZulu-Natal (South Africa).

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The impact of population dynamics on the population HIV care cascade: results from the ANRS 12249 Treatment as Prevention trial in rural KwaZulu-Natal (South Africa).

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