Impact of Early Antiretroviral Treatment Initiation on Performance of Cross-Sectional Incidence Assays.
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ABSTRACT:
SUBMITTER: Klock E
PROVIDER: S-EPMC7398433 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAntiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays.MethodsSamples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or <250 cells/mm or an AIDS-defining illness (delayed ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result).ResultsTen (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection.ConclusionsFalse-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.
| S-EPMC5499248 | biostudies-literature
Project description:BackgroundMulti-assay algorithms (MAAs) are used to estimate population-level HIV incidence and identify individuals with recent infection. Many MAAs use low viral load (VL) as a biomarker for long-term infection. This could impact incidence estimates in settings with high rates of early HIV treatment initiation. We evaluated the performance of two MAAs that do not include VL.MethodsSamples were collected from 219 seroconverters (infected < 1 year) and 4376 non-seroconverters (infected > 1 year) in the HPTN 071 (PopART) trial; 28.8% of seroconverter samples and 73.2% of non-seroconverter samples had VLs ≤ 400 copies/mL. Samples were tested with the Limiting Antigen Avidity assay (LAg) and JHU BioRad-Avidity assays. Antibody reactivity to two HIV peptides was measured using the MSD U-PLEX assay. Two MAAs were evaluated that do not include VL: a MAA that includes the LAg-Avidity assay and BioRad-Avidity assay (LAg + BR) and a MAA that includes the LAg-Avidity assay and two peptide biomarkers (LAg + PepPair). Performance of these MAAs was compared to a widely used MAA that includes LAg and VL (LAg + VL).ResultsThe incidence estimate for LAg + VL (1.29%, 95% CI: 0.97-1.62) was close to the observed longitudinal incidence (1.34% 95% CI: 1.17-1.53). The incidence estimates for the other two MAAs were higher (LAg + BR: 2.56%, 95% CI 2.01-3.11; LAg + PepPair: 2.84%, 95% CI: 1.36-4.32). LAg + BR and LAg + PepPair also misclassified more individuals infected > 2 years as recently infected than LAg + VL (1.2% [42/3483 and 1.5% [51/3483], respectively, vs. 0.2% [6/3483]). LAg + BR classified more seroconverters as recently infected than LAg + VL or LAg + PepPair (80 vs. 58 and 50, respectively) and identified ~ 25% of virally suppressed seroconverters as recently infected.ConclusionsThe LAg + VL MAA produced a cross-sectional incidence estimate that was closer to the longitudinal estimate than two MAAs that did not include VL. The LAg + BR MAA classified the greatest number of individual seroconverters as recently infected but had a higher false recent rate.
| S-EPMC9652879 | biostudies-literature
Project description:IntroductionRecent WHO guidance advocates for early antiretroviral therapy (ART) initiation at higher CD4 counts to improve survival and reduce HIV transmission. We sought to quantify how the cost-effectiveness and epidemiological impact of early ART strategies in India are affected by attrition throughout the HIV care continuum.MethodsWe constructed a dynamic compartmental model replicating HIV transmission, disease progression and health system engagement among Indian adults. Our model of the Indian HIV epidemic compared implementation of early ART initiation (i.e. initiation above CD4 ≥350 cells/mm(3)) with delayed initiation at CD4 ≤350 cells/mm(3); primary outcomes were incident cases, deaths, quality-adjusted-life-years (QALYs) and costs over 20 years. We assessed how costs and effects of early ART initiation were impacted by suboptimal engagement at each stage in the HIV care continuum.ResultsAssuming "idealistic" engagement in HIV care, early ART initiation is highly cost-effective ($442/QALY-gained) compared to delayed initiation at CD4 ≤350 cells/mm(3) and could reduce new HIV infections to <15,000 per year within 20 years. However, when accounting for realistic gaps in care, early ART initiation loses nearly half of potential epidemiological benefits and is less cost-effective ($530/QALY-gained). We project 1,285,000 new HIV infections and 973,000 AIDS-related deaths with deferred ART initiation with current levels of care-engagement in India. Early ART initiation in this continuum resulted in 1,050,000 new HIV infections and 883,000 AIDS-related deaths, or 18% and 9% reductions (respectively), compared to current guidelines. Strengthening HIV screening increases benefits of earlier treatment modestly (1,001,000 new infections; 22% reduction), while improving retention in care has a larger modulatory impact (676,000 new infections; 47% reduction).ConclusionsEarly ART initiation is highly cost-effective in India but only has modest epidemiological benefits at current levels of care-engagement. Improved retention in care is needed to realize the full potential of earlier treatment.
| S-EPMC4592848 | biostudies-literature
Project description:Germinal center resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV) replication. But the dynamics of germinal centers upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post-SIV infection are not fully understood.Sequential lymph node biopsies (n?=?10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART initiation. These tissues and cells were analyzed for frequencies of TFH cells and assignment of germinal center scores.Modest but significant increases in TFH cells and hyperplastic follicles with large germinal centers were noted during the acute phase of SIV infection (week 5/pre-ART). However, 6 weeks after ART initiation, substantial increases in germinal center TFH cells, germinal center B cells, hyperplastic follicles with large germinal centers, and abundant local IL-21 production were observed, whereas levels of SIV RNA and DNA of lymph nodes had decreased to barely detectable values along with barely detectable levels of SIV antibody-producing cells. An additional 6 weeks of ART did not appreciably decrease germinal center TFH or germinal center scores.Thus, although early ART rapidly controls SIV replication, it does not regulate early lymphoid activation, which may contribute to the seeding and magnitude of viral reservoirs.
| S-EPMC5557084 | biostudies-literature
Project description:IntroductionCross-sectional incidence testing is used to estimate population-level HIV incidence and measure the impact of prevention interventions. There are limited data evaluating the accuracy of estimates in settings where antiretroviral therapy coverage and levels of viral suppression are high. Understanding cross-sectional incidence estimates in these settings is important as viral suppression can lead to false recent test results. We compared the accuracy of multi-assay algorithms (MAA) for incidence estimation to that observed in the community-randomized HPTN 071 (PopART) trial, where the majority of participants with HIV infection were virally suppressed.MethodsHIV incidence was assessed during the second year of the study, and included only individuals who were tested for HIV at visits 1 and 2 years after the start of the study (2016-2017). Incidence estimates from three MAAs were compared to the observed incidence between years 1 and 2 (MAA-C: LAg-Avidity <2.8 ODn + BioRad Avidity Index <95% + VL >400 copies/ml; LAg+VL MAA: LAg-Avidity <1.5 ODn + VL >1000 copies/ml; Rapid+VL MAA: Asanté recent rapid result + VL >1000 copies/ml). The mean duration of recent infection (MDRI) used for the three MAAs was 248, 130 and 180 days, respectively.Results and discussionThe study consisted of: 15,845 HIV-negative individuals; 4406 HIV positive at both visits; and 221 who seroconverted between visits. Viral load (VL) data were available for all HIV-positive participants at the 2-year visit. Sixty four (29%) of the seroconverters and 3227 (72%) prevelant positive participants were virally supressed (<400 copies/ml). Observed HIV incidence was 1.34% (95% CI: 1.17-1.53). Estimates of incidence were similar to observed incidence for MAA-C, 1.26% (95% CI: 1.02-1.51) and the LAg+VL MAA, 1.29 (95% CI: 0.97-1.62). Incidence estimated by the Rapid+VL MAA was significantly lower than observed incidence (0.92%, 95% CI: 0.69-1.15, p<0.01).ConclusionsMAA-C and the LAg+VL MAA provided accurate point estimates of incidence in this cohort with high levels of viral suppression. The Rapid+VL significantly underestimated incidence, suggesting that the MDRI recommended by the manufacturer is too long or the assay is not accurately detecting enough recent infections.
| S-EPMC8666582 | biostudies-literature
Project description:BackgroundIncreased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell count 350/?l. We investigated what would be required to reduce HIV incidence in MSM to below 1 per 1000 person-years (i.e. <535 new infections per year) by 2030, and whether this is likely to be cost-effective.MethodsA dynamic, individual-based simulation model was calibrated to multiple data sources on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex.ResultsFor ART use to result in an incidence of close to 1/1000 person-years requires the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men with viral suppression to 80%, and it would be 90%, if ART is initiated at diagnosis. The scenarios required for such a policy to be cost-effective are presented.ConclusionThis analysis provides targets for the proportion of all HIV-positive MSM with viral suppression required to achieve substantial reductions in HIV incidence.
| S-EPMC5515630 | biostudies-literature
Project description:BackgroundHIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations.MethodsWe analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis.FindingsBetween Oct 1, 2012, and Dec 19, 2013, we recruited 26,503 participants, 12,022 men who have sex with men and 14,481 people who inject drugs. Median incidence of HIV was 0·87% (IQR 0·40-1·17) in men who have sex with men and 1·43% (0·60-4·00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0·81, 95% CI 0·62-0·91; p<0·0001) than all other measures, although correlation was significant with aware viral load (0·59, 0·27-0·79; p=0·001), population viral load (0·51, 0·16-0·74; p=0·007), and population ART coverage (-0·54, -0·76 to -0·20; p=0·004). In-care viral load was not correlated with HIV incidence (0·29, -0·10 to 0·60; p=0·14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4·34%, and ART use in HIV-positive individuals would need to increase by 19·5%.InterpretationPrevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme.FundingUS National Institutes of Health, Elton John AIDS Foundation.
| S-EPMC4863069 | biostudies-literature
Project description:BACKGROUND:Antiretroviral treatment (ART) reduces HIV infectiousness but the effect of early ART on sexual behaviour is unclear. METHODS:We assessed, within the START randomized trial that enrolled HIV-positive adults with CD4 cell count greater than 500?cells/?l, the effect of early (immediate) versus deferred ART on: condomless sex with HIV-serodifferent partners (CLS-D); all condomless sex (CLS); HIV transmission-risk sex (CLS-D-HIV risk, defined as CLS-D and: not on ART or started ART <6 months ago or viral load greater than 200 copies/ml or no viral load in past 6 months), during 2-year follow-up. Month-12 CLS-D (2010-2014) was the primary outcome. RESULTS:Among 2562 MSM, there was no difference between immediate and deferred arms in CLS-D at month 12 [12.6 versus 13.1%; difference (95% CI): -0.4% (-3.1 to 2.2%), P?=?0.75] or month 24, or in CLS. Among 2010 heterosexual men and women, CLS-D at month 12 tended to be higher in the immediate versus deferred arm [10.8 versus 8.3%; difference:2.5% (-0.1 to 5.2%), P?=?0.062]; the difference was greater at month 24 [9.3 versus 5.6%; difference: 3.7% (1.0 to 6.4%), P?=?0.007], at which time CLS was higher in the immediate arm (20.7 versus 15.7%, P?=?0.013). CLS-D-HIV risk at month 12 was substantially lower in the immediate versus deferred arm for MSM [0.2 versus 11%; difference: -10.7% (-12.5 to -8.9%), P?<?0.001] and heterosexuals [0.6% versus 7.7%; difference: -7.0% (-8.8 to -5.3%), P?<?0.001], because of viral suppression on ART. CONCLUSION:A strategy of early ART had no effect on condomless sex with HIV-serodifferent partners among MSM, but resulted in modestly higher prevalence among heterosexuals. However, among MSM and heterosexuals, early ART resulted in a substantial reduction in HIV-transmission-risk sex, to a very low absolute level.
| S-EPMC6882545 | biostudies-literature
Project description:It is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART.We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis.Among the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/?l; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/?l, P = 0.004).Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits.
| S-EPMC4827808 | biostudies-literature
Project description:IntroductionCommencing breastfeeding within one hour of birth is defined as early initiation of breastfeeding (EIBF). Both the mother and child benefit from EIBF. This study aims to identify the predictors of EIBF among Indonesian women.MethodsThis paper analyses data from a weighted sample of 6,616 women collected at the Indonesia Demographic and Health Survey (IDHS) 2017.The frequency of EIBF is measured by the proportion of children born in the two years preceding the survey who received breastmilk within one hour of birth. The analysis uses bivariate and multivariate logistic regression for complex sample designs, adjusted for confounders to examine the relationship of EIBF with women's individual, household and community level characteristics.ResultsOverall, 57% (95% CI: 54.9%-58.2%) of the children born in the two years preceding the survey had EIBF. Statistically significant (p<0.05) predictors of EIBF are women's non-working status, second or higher order of the birth of the most recent child, average or large size of the most recent child at birth, poor status of the household and non-agricultural work of the woman's husband; while statistically highly significant (p<0.01) predictors are skin-to-skin contact with the new-born (OR: 2.62; 95% CI: 2.28-3.00), Caesarean deliveries (OR: 0.47; 95% CI: 0.40-0.56), and skilled birth attendants (OR: 1.83; 95% CI: 1.65-2.08). Caesarean deliveries reduce the likelihood of EIBF by half compared to vaginal deliveries. Women's age, education or rural-urban residence display no statistically significant relationship with EIBF.ConclusionSkin-to-skin contact, mode of delivery and type of birth attendance exert the strongest influence on EIBF in Indonesia in 2017. EIBF should be continuously promoted and supported particularly among mothers who do not have early skin-to-skin contact with their new-born, who have Caesarean deliveries and who have no skilled birth attendant.
| S-EPMC7514028 | biostudies-literature