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      Estimating Incidence from Prevalence in Generalised HIV Epidemics: Methods and Validation

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          Abstract

          Background

          HIV surveillance of generalised epidemics in Africa primarily relies on prevalence at antenatal clinics, but estimates of incidence in the general population would be more useful. Repeated cross-sectional measures of HIV prevalence are now becoming available for general populations in many countries, and we aim to develop and validate methods that use these data to estimate HIV incidence.

          Methods and Findings

          Two methods were developed that decompose observed changes in prevalence between two serosurveys into the contributions of new infections and mortality. Method 1 uses cohort mortality rates, and method 2 uses information on survival after infection. The performance of these two methods was assessed using simulated data from a mathematical model and actual data from three community-based cohort studies in Africa. Comparison with simulated data indicated that these methods can accurately estimates incidence rates and changes in incidence in a variety of epidemic conditions. Method 1 is simple to implement but relies on locally appropriate mortality data, whilst method 2 can make use of the same survival distribution in a wide range of scenarios. The estimates from both methods are within the 95% confidence intervals of almost all actual measurements of HIV incidence in adults and young people, and the patterns of incidence over age are correctly captured.

          Conclusions

          It is possible to estimate incidence from cross-sectional prevalence data with sufficient accuracy to monitor the HIV epidemic. Although these methods will theoretically work in any context, we have able to test them only in southern and eastern Africa, where HIV epidemics are mature and generalised. The choice of method will depend on the local availability of HIV mortality data.

          Abstract

          Timothy Hallett and colleagues develop and test two user-friendly methods to estimate HIV incidence based on changes in cross-sectional prevalence, using either mortality rates or survival after infection.

          Editors' Summary

          Background.

          More than 25 million people have died from AIDS and about 33 million people are currently infected with human immunodeficiency virus (HIV, the virus that causes AIDS). Faced with this threat to human health, governments and international agencies are working together to halt the AIDS epidemic. An important part of this effort is HIV surveillance. The spread of HIV needs to be monitored to assess the impact of interventions (for example, the provision of antiretroviral drugs) and to plan for current and future health care needs. HIV surveillance in countries where the epidemic has spread beyond specific groups into the whole population (a generalized epidemic) has mainly relied on determining the prevalence of HIV infection (the fraction of the population that is infected) among women attending antenatal clinics. Recently, however, household health surveys (for example, the Demographic and Health Surveys) have begun to use blood testing for antibodies to the AIDS virus (serological testing) to provide more accurate estimates of HIV prevalence in the general adult population.

          Why Was This Study Done?

          Although prevalence estimates provide useful information about the HIV epidemic, another important indicator is incidence—the number of new infections occurring during a specific time period. Incidence measurements provide more information about temporal changes in the epidemic and transmission patterns and allow public-health experts to make better predictions of future health care needs. But, whereas prevalence can be measured with anonymized serological surveys, individuals would have to be identified and followed up in repeat serological surveys to provide a direct measurement of incidence. This is expensive and hard to achieve in many settings. In this study, therefore, the researchers develop and validate two mathematical methods to estimate HIV incidence in generalized HIV epidemics from prevalence data.

          What Did the Researchers Do and Find?

          Changes in the fraction of the population living with HIV (prevalence) can occur not only because of changes in the rate of new infections (incidence), but also because mortality rates are much higher for infected individuals than others. The researchers' methods disentangle the contributions to HIV prevalence (as measured in serological surveys) made by new infections from those due to deaths from AIDS and other causes. Their first method incorporates information on death rates collected in cohort studies of HIV infection (cohort studies investigate outcomes in groups of people); their second method uses information on survival after HIV infection, also collected in long-running cohort studies. The accuracy of both methods was assessed using computer-simulated data and actual data on HIV prevalence and incidence collected in three community-based cohort studies in Zimbabwe and Uganda (countries with generalized but declining HIV epidemics) and Tanzania (a country with a generalized, stable epidemic). Both methods provided accurate estimates of HIV incidence from the simulated data. Using the data collected in Africa, the mean difference between actual measurements of incidence and the estimate provided by method 1 was 19%; for method 2 it was 14%. In addition, the measured and estimated incidences were in good agreement for all age groups.

          What Do These Findings Mean?

          These findings suggest HIV incidence rates can be estimated from repeat surveys of prevalence with sufficient accuracy to monitor the HIV epidemic. The accuracy of the estimates across all age groups is particularly important because knowledge of the age-related risk pattern provides the information on transmission patterns that is needed to design effective intervention programs. Because these methods were tested using data only from southern and eastern Africa where the HIV epidemic is mature and generalized, they may not work as well in regions where the epidemic is restricted to subsets of the population. Other factors that might affect their accuracy include the amount of international migration and the uptake of antiretroviral therapies. Nevertheless, with the increased availability of serial measurements of serological prevalence, these new methods for estimating HIV incidence from HIV prevalence could prove extremely useful for monitoring the progress of national HIV epidemics and for guiding HIV control programs. The authors include spreadsheets that can be used to calculate incidence by either method from consecutive survey data.

          Additional Information.

          Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050080.

          Related collections

          Most cited references37

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          • Abstract: found
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          HIV decline associated with behavior change in eastern Zimbabwe.

          Few sub-Saharan African countries have witnessed declines in HIV prevalence, and only Uganda has compelling evidence for a decline founded on sexual behavior change. We report a decline in HIV prevalence in eastern Zimbabwe between 1998 and 2003 associated with sexual behavior change in four distinct socioeconomic strata. HIV prevalence fell most steeply at young ages-by 23 and 49%, respectively, among men aged 17 to 29 years and women aged 15 to 24 years-and in more educated groups. Sexually experienced men and women reported reductions in casual sex of 49 and 22%, respectively, whereas recent cohorts reported delayed sexual debut. Selective AIDS-induced mortality contributed to the decline in HIV prevalence.
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            Quantitative detection of increasing HIV type 1 antibodies after seroconversion: a simple assay for detecting recent HIV infection and estimating incidence.

            We have devised a simple enzyme immunoassay (EIA) that detects increasing levels of anti-HIV IgG after seroconversion and can be used for detecting recent HIV-1 infection. Use of a branched peptide that included gp41 immunodominant sequences from HIV-1 subtypes B, E, and D allowed similar detection of HIV-specific antibodies among various subtypes. Because of the competitive nature of the capture EIA, a gradual increase in the proportion of HIV-1-specific IgG in total IgG was observed for 2 years after seroconversion. This was in contrast to results obtained with the conventional EIA using the same antigen in solid phase, which plateaus soon after seroconversion. The assay was used to test 622 longitudinal specimens from 139 incident infections in the United States (subtype B) and in Thailand (subtypes B and E). The assay was also performed with an additional 8 M urea incubation step to assess the contribution of high-avidity antibodies. Normalized optical density (OD-n) was calculated (ODspecimen/ODcalibrator), using a calibrator specimen. An incremental analysis indicated that a cutoff of 1.0 OD-n and a seroconversion period of 160 days offered the best combination of sensitivity and specificity for classifying incident or long-term infections. The urea step increased the seroconversion period to 180 days with similar sensitivity and specificity. Separate analysis of B and E subtype specimens yielded the same optimal OD-n threshold and similar seroconversion periods. The assay was further validated in African specimens (subtypes A, C, and D) where the observed incidence was within 10% of the expected incidence. This assay should be useful for detecting recent HIV-1 infection and for estimating incidence among diverse HIV-1 subtypes worldwide.
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              Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy.

              To estimate survival patterns after HIV infection in adults in low and middle-income countries. An analysis of pooled data from eight different studies in six countries. HIV seroconverters were included from eight studies (three population-based, two occupational, and three clinic cohorts) if they were at least 15 years of age, and had no more than 4 years between the last HIV-negative and subsequent HIV-positive test. Four strata were defined: East African cohorts; South African miners cohort; Thai cohorts; Haitian clinic cohort. Kaplan-Meier functions were used to estimate survival patterns, and Weibull distributions were used to model and extend survival estimates. Analyses examined the effect of site, age, and sex on survival. From 3823 eligible seroconverters, 1079 deaths were observed in 19 671 person-years of follow-up. Survival times varied by age and by study site. Adjusting to age 25-29 years at seroconversion, the median survival was longer in South African miners: 11.6 years [95% confidence interval (CI) 9.8-13.7] and East African cohorts: 11.1 years (95% CI 8.7-14.2) than in Haiti: 8.3 years (95% CI 3.2-21.4) and Thailand: 7.5 years (95% CI 5.4-10.4). Survival was similar for men and women, after adjustment for age at seroconversion and site. Without antiretroviral therapy, overall survival after HIV infection in African cohorts was similar to survival in high-income countries, with a similar pattern of faster progression at older ages at seroconversion. Survival appears to be significantly worse in Thailand where other, unmeasured factors may affect progression.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                pmed
                plme
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                April 2008
                8 April 2008
                : 5
                : 4
                : e80
                Affiliations
                [1 ] Imperial College London, London, United Kingdom
                [2 ] London School of Hygiene and Tropical Medicine, London, United Kingdom
                [3 ] National Institute for Medical Research, Mwanza, Tanzania
                [4 ] Medical Research Council/Uganda Virus Research Institute, Uganda Research Unit on AIDS, Entebbe, Uganda
                [5 ] Biomedical Research and Training Institute, Harare, Zimbabwe
                [6 ] World Health Organization, Geneva, Switzerland
                Joint United Nations Programme on HIV/AIDS, Switzerland
                Author notes
                * To whom correspondence should be addressed. E-mail: timothy.hallett@ 123456imperial.ac.uk
                Article
                07-PLME-RA-0491R3 plme-05-04-07
                10.1371/journal.pmed.0050080
                2288620
                18590346
                b123f61e-e053-4cfb-ac3c-6908ffffda77
                Copyright: © 2008 Hallett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 21 May 2007
                : 15 February 2008
                Page count
                Pages: 12
                Categories
                Research Article
                Infectious Diseases
                Mathematics
                Public Health and Epidemiology
                Epidemiology
                HIV Infection/AIDS
                Public Health
                Statistics
                International Health
                Custom metadata
                Hallett TB, Zaba B, Todd J, Lopman B, Wambura M, et al. (2008) Estimating incidence from prevalence in generalised HIV epidemics: Methods and validation. PLoS Med 5(4): e80. doi: 10.1371/journal.pmed.0050080

                Medicine
                Medicine

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