Author s response to reviews Title: Is Zimbabwe ready to transition from anonymous unlinked sero-surveillance to using Prevention of Mother to Child Transmission of HIV (PMTCT) program data for HIV Surveillance?: Results of PMTCT Utility Study, 2012 Authors: Elizabeth Gonese (egonese@cdc.gov) Angela Mushavi (mushavia@yahoo.co.uk) More Mungati (mungatim@yahoo.com) Mutsa Mhangara (mutsa.mhangara@gmail.com) Janet Dzangare (janet.dzangare@gmail.com) Owen Mugurungi (atp.director@ymail.com) Jacob Dee (idi0@cdc.gov) Peter Kilmarx (peter.kilmarx@nih.gov) Gerald Shambira (gshambira@yahoo.com) Mufuta Tshimanga (mufutatshimanga@gmail.com) John Hargrove (jhargrove@sun.ac.za) Version: 1 Date: 07 Jan 2016 Author s response to reviews: Responses to Reviewers Reviewer 1 Takafira Mduluza
Reviewer #1: Unlinked and anonymous HIV testing (UAT) for surveillance among "pregnant women" who routinely attend ANC sentinel sites can provide valuable information about the burden of HIV and trends in HIV prevalence in a community and the strategy is not very expensive since the surveillance would be embedded in a routine exercise. Even though antenatal clinics can provide an accessible cross-section of healthy, sexually active women in the general population, the HIV data from ANC surveillance cannot generally represent the source community. Any community displays different dynamics from both females and males including the effects from the different age groups. Epidemiologic information provided by ANC somehow may mirror the community the argument still stands that there is another sector that has been considered in UAT unlike the only gender of the surveillance ANC as alluded to in this article. The argument is not compelling enough even though this has been talked about UAT for surveillance cannot be replaced by the ANC clinic. The information reported here is not well supported but even detailing the dynamics of the UZT population unlike the directional explanation showing contribution of the ANC data for community HIV trends. I would recommend that the authors give strata of the population when UAT is used as compared to ANC and even though in consideration by WHO to cut on costs instead of the general UAT surveillances, justification is required unless the reports would specifically be limited to trends for women population. Response: Thank you for thorough review of our manuscript. We would like to point out that we are talking about replacing UAT surveillance with PMCTC Program data. The relationship between HIV prevalence in pregnant women and that of women in the general population is a different matter which we are not attempting to address in this current paper. The basis of replacing UAT with PMTCT program data arises from the ethical issue that in this day and age when Antiretroviral therapy is widely available for the health of a pregnant woman, there is no reason why an HIV positive woman should not benefit from this treatment simply because we have chosen to conduct an anonymous and unlinked HIV test (UAT) for surveillance purposes. Furthermore, the acceptance rates for PMTCT testing and receipt of results are 95%, which would mean that repeating a test in UAT surveillance instead of using the PMTCT program data is an additional cost that does not seem justified. We have in this paper advocated for the continuation of analysis of PMTCT program data as an important source of HIV prevalence trends in this critical population that provides complimentary data to population based surveys.
We would like to refer you to an earlier publication, Gonese et al (2010) titled Comparison of HIV Prevalence Estimates for Zimbabwe from Antenatal Clinic Surveillance (2006) and the 2005 06 Zimbabwe Demographic and Health Survey. We concluded that although the prevalence in ANC surveillance was similar to estimates among men and women 15-49 years in the general population, there was need to validate these estimates using population surveys. Therefore we continue to advocate that we should collect HIV prevalence trend data in the populations of pregnant women. However, there is need to change the methods from UAT to use of PMCT program data, which is the focus of this current paper. Definition of abbreviations PPA and NPA should be given early in the use. On page 12 in the Methods under Data Analysis, Comparison of prevalence HIV estimates derived from program data and UAT surveillance, we have expanded the last sentence and it now reads; These data were cross-tabulated to calculate positive percent agreement (same calculation as sensitivity) and negative percent agreement (the same calculation as specificity) of PMTCT and UAT surveillance HIV testing. This gives a measure of the proportion of individual cases giving results in UAT and PMTCT as either both positive or negative results. Pg6 line 26: Incomplete sentence, requires qualification. We believe you are referring to the sentence below. Data from the three month pre-survey period were not included in this paper. In the main data collection, we reviewed data in PMTCT registers up to a period of 3 months prior to the concurrent conduct of UAT surveillance and PMTCT program data review. We wanted to assess the completeness of reporting for each site. Because this period did not have UAT data, we did not include any of the findings in this report. To avoid further confusion, we have deleted this sentence from the manuscript Pg 6 line 12 and line 40. Authors should refrain starting sentence with Because let alone starting a paragraph. Thank you, we have reworded and now read as;
PMTCT programs collect socio-demographic and HIV testing information similar to that collected by ANC HSS hence, many countries are considering the use of PMTCT program data to complement or replace UAT surveillance. To avoid repetition and starting a sentence with the word Because, we have deleted and rephrased sentence to read; As a result of this, Zimbabwe has considered transitioning to using PMTCT data to monitor trends in the HIV epidemic. Pg 7 line 36 repetition of the of the Thank you we have deleted. Pg 17 line 25-36 reorganize the presentation instead of such short paragraphs. We have re-organised the discussion in order to avoid repetition I don't understand where there is potential for false positives from using an EIA based algorithm. Considering that the EIA should be very sensitive if undertaken by well-trained experienced personnel. False positives relate to the specificity of an assay i.e If a person does not have the disease how often will the test be negative (true negative rate)?. Each assay has its specificity and it desirable to use assays that have a high specificity in order to reduce false positives. In this regard, the training of personnel is not the sole factor in ruling out false positives.
Reference section is not well written. Given list should avoid incomplete author names and titles of the articles should be given in full. Have rectified Reviewer #2: Review report Gonese and colleagues attempt to present an interesting article to evaluate the utility of PMTCT programme data to replace the unlinked anonymous testing for HIV surveillance in Zimbabwe. The aim of the article is clearly exposed and well defined and it is of great interest to consider the use of PMTCT program data to complement or replace the UAT for HIV surveillance in this population. However there are minor essential revisions that must be corrected and clarified before it being accepted for publication. In Methods 1. It may be worth to perform a diagram to show exactly the number of women included and excluded for the comparison of prevalence estimations from the UAT surveillance and PMTCT program Data. It will complement the presentation of the results. Given the length and number of tables in the manuscript, we had opted not to include this diagram. However, if this will add value to manuscript we have attached Figure 1 2. In Data collection tools and methods,( Page 7, Lines 40-44) say: The initial test for HIV detection was conducted using AniLabsytems.All non-reactive result were reported negative as final result... Question: Was there a low percentage of these negative samples re-analysed using other test, to discard false negative results? All samples that were positive on the first test AniLabsytems were confirmed using a second test Enzygnost. Of the 183 samples which were initially positive only 89 remained positive, meaning that 94 were discrepant and needed re-testing.
3. Results. Comparison of UAT and PMTCT Program Data. - There are some results described in the text (Page 15, Lines 8-20) that are different to those showed in Table 1 and Abstract. Some examples: The number of women sampled for the HIV prevalence analysis according the UAT surveillance testing and the PMTCT program data. The HIV prevalence according PMTCT data in Mutoko.. The number of sites in which the UAT surveillance result was slightly lower than the PMTCT program result. Please correct or clarify. - There are some results described in the text (Page 15, Lines 29-44) that are different to those showed in Table 2. Some examples: Number of women who were HIV positive according to PMTCT HIV results but ELISA negative (UAT), number of women who were HIV test negative according PMTCT but ELISA positive (UAT),number of sites that had a negative agreement below 98%. Please correct or clarify. - There are some results described in text (Page 16, Lines 10-23) that are different to those showed in Table 3. Some examples: Ranges of overall median HIV prevalence, Number of sites that reported bias of 0.0%. Please correct or clarify. Thank you very much for the thorough review of our results. We have made substantial changes firstly to the Methods Section under inclusion and exclusion criteria. We realized, that we had provided a lot of information on the data cleaning which we now feel is not necessary to this manuscript. To this end, we have re-organised the text and ensured concordance of the denominators used in each analysis and the associated results. Furthermore, we have provided Figure 1 to improve on clarity Discussion (Page 17-19) The discussion and conclusions are supported by the data presented and the discussion is based on relevant references. However could be important to include a small discussion of the results obtained after re testing of the samples that increased the positive and negative percent of agreement. Also could be
interesting to discuss more the higher % of HIV prevalence when analysing the PMTCT data and if this can be in part explained by the higher number of false positive results. Again following revisions in results, we have re-organised our discussion include possible explanations and hypothesis emanating from the evaluation References - Some references are not well written. Please correct them. Have corrected references Other General Comments. -There are some words and sentences repeated. Please review all the manuscript. Thank you for the thorough review. We have read through and re-organised sentences, deleted duplications and ensured smooth flow of manuscript -Some abbreviations are not defined. Please add them in the text and in the abbreviation section. We have added the missing abbreviations as suggested on page 21 of the Modified version Authors Contributions: Your 'Authors Contributions' section must detail the individual contribution for each individual author listed on your manuscript. We have detailed authors contributions on pg 20 of Clean document