HIV and Menopause: A Systematic Review of the Effects of HIV Infection on Age at Menopause and the Effects of Menopause on Response to Antiretroviral Therapy
Identifieur interne : 002804 ( Pmc/Corpus ); précédent : 002803; suivant : 002805HIV and Menopause: A Systematic Review of the Effects of HIV Infection on Age at Menopause and the Effects of Menopause on Response to Antiretroviral Therapy
Auteurs : Kentaro Imai ; Madeline Y. Sutton ; Rennatus Mdodo ; Carlos Del RioSource :
- Obstetrics and Gynecology International [ 1687-9589 ] ; 2013.
Abstract
More than half of persons living with HIV infection in the United States (U.S.) will be ≥50 years of age by 2020, including postmenopausal women. We conducted a systematic literature review about the effects of (1) HIV infection on age at menopause and (2) menopause on antiretroviral therapy (ART) response, in order to inform optimal treatment strategies for menopausal women living with HIV infection. We used the Ovid Medline database from 1980 to 2012. We included studies that focused on HIV-infected persons, included postmenopausal women, and reported outcome data for either age at menopause or response to ART across menopause. We identified six original research articles for age at menopause and five for response to ART across menopause. Our review revealed that current data were conflicting and inconclusive; more rigorous studies are needed. Disentangling the effects of menopause requires well-designed studies with adequate numbers of HIV-infected and HIV-uninfected women, especially disproportionately affected women of color. Future studies should follow women from premenopause through menopause, use both surveys and laboratory measurements for menopause diagnoses, and control for confounders related to normal aging processes, in order to inform optimal clinical management for menopausal women living with HIV.
Url:
DOI: 10.1155/2013/340309
PubMed: 24454386
PubMed Central: 3880754
Links to Exploration step
PMC:3880754Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">HIV and Menopause: A Systematic Review of the Effects of HIV Infection on Age at Menopause and the Effects of Menopause on Response to Antiretroviral Therapy</title><author><name sortKey="Imai, Kentaro" sort="Imai, Kentaro" uniqKey="Imai K" first="Kentaro" last="Imai">Kentaro Imai</name><affiliation><nlm:aff id="I1">Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA</nlm:aff></affiliation></author><author><name sortKey="Sutton, Madeline Y" sort="Sutton, Madeline Y" uniqKey="Sutton M" first="Madeline Y." last="Sutton">Madeline Y. Sutton</name><affiliation><nlm:aff id="I2">Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</nlm:aff></affiliation></author><author><name sortKey="Mdodo, Rennatus" sort="Mdodo, Rennatus" uniqKey="Mdodo R" first="Rennatus" last="Mdodo">Rennatus Mdodo</name><affiliation><nlm:aff id="I2">Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</nlm:aff></affiliation></author><author><name sortKey="Del Rio, Carlos" sort="Del Rio, Carlos" uniqKey="Del Rio C" first="Carlos" last="Del Rio">Carlos Del Rio</name><affiliation><nlm:aff id="I4">Hubert Department of Global Health, Emory University, Atlanta, GA 30333, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24454386</idno><idno type="pmc">3880754</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880754</idno><idno type="RBID">PMC:3880754</idno><idno type="doi">10.1155/2013/340309</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002804</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002804</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">HIV and Menopause: A Systematic Review of the Effects of HIV Infection on Age at Menopause and the Effects of Menopause on Response to Antiretroviral Therapy</title><author><name sortKey="Imai, Kentaro" sort="Imai, Kentaro" uniqKey="Imai K" first="Kentaro" last="Imai">Kentaro Imai</name><affiliation><nlm:aff id="I1">Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA</nlm:aff></affiliation></author><author><name sortKey="Sutton, Madeline Y" sort="Sutton, Madeline Y" uniqKey="Sutton M" first="Madeline Y." last="Sutton">Madeline Y. Sutton</name><affiliation><nlm:aff id="I2">Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</nlm:aff></affiliation></author><author><name sortKey="Mdodo, Rennatus" sort="Mdodo, Rennatus" uniqKey="Mdodo R" first="Rennatus" last="Mdodo">Rennatus Mdodo</name><affiliation><nlm:aff id="I2">Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</nlm:aff></affiliation><affiliation><nlm:aff id="I3">Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</nlm:aff></affiliation></author><author><name sortKey="Del Rio, Carlos" sort="Del Rio, Carlos" uniqKey="Del Rio C" first="Carlos" last="Del Rio">Carlos Del Rio</name><affiliation><nlm:aff id="I4">Hubert Department of Global Health, Emory University, Atlanta, GA 30333, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Obstetrics and Gynecology International</title><idno type="ISSN">1687-9589</idno><idno type="eISSN">1687-9597</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>More than half of persons living with HIV infection in the United States (U.S.) will be ≥50 years of age by 2020, including postmenopausal women. We conducted a systematic literature review about the effects of (1) HIV infection on age at menopause and (2) menopause on antiretroviral therapy (ART) response, in order to inform optimal treatment strategies for menopausal women living with HIV infection. We used the Ovid Medline database from 1980 to 2012. We included studies that focused on HIV-infected persons, included postmenopausal women, and reported outcome data for either age at menopause or response to ART across menopause. We identified six original research articles for age at menopause and five for response to ART across menopause. Our review revealed that current data were conflicting and inconclusive; more rigorous studies are needed. Disentangling the effects of menopause requires well-designed studies with adequate numbers of HIV-infected and HIV-uninfected women, especially disproportionately affected women of color. Future studies should follow women from premenopause through menopause, use both surveys and laboratory measurements for menopause diagnoses, and control for confounders related to normal aging processes, in order to inform optimal clinical management for menopausal women living with HIV.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Porter, K" uniqKey="Porter K">K Porter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hacker, Ma" uniqKey="Hacker M">MA Hacker</name></author><author><name sortKey="Petersen, Ml" uniqKey="Petersen M">ML Petersen</name></author><author><name sortKey="Enriquez, M" uniqKey="Enriquez M">M Enriquez</name></author><author><name sortKey="Bastos, Fi" uniqKey="Bastos F">FI Bastos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="High, Kp" uniqKey="High K">KP High</name></author><author><name sortKey="Brennan Ing, M" uniqKey="Brennan Ing 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Obstet Gynecol Int</journal-id><journal-id journal-id-type="iso-abbrev">Obstet Gynecol Int</journal-id><journal-id journal-id-type="publisher-id">OGI</journal-id><journal-title-group><journal-title>Obstetrics and Gynecology International</journal-title></journal-title-group><issn pub-type="ppub">1687-9589</issn><issn pub-type="epub">1687-9597</issn><publisher><publisher-name>Hindawi Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24454386</article-id><article-id pub-id-type="pmc">3880754</article-id><article-id pub-id-type="doi">10.1155/2013/340309</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title>HIV and Menopause: A Systematic Review of the Effects of HIV Infection on Age at Menopause and the Effects of Menopause on Response to Antiretroviral Therapy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Imai</surname><given-names>Kentaro</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sutton</surname><given-names>Madeline Y.</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Mdodo</surname><given-names>Rennatus</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref><xref ref-type="aff" rid="I3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>del Rio</surname><given-names>Carlos</given-names></name><xref ref-type="aff" rid="I4"><sup>4</sup></xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Rollins School of Public Health, Emory University, Atlanta, GA 30333, USA</aff><aff id="I2"><sup>2</sup>Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</aff><aff id="I3"><sup>3</sup>Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA</aff><aff id="I4"><sup>4</sup>Hubert Department of Global Health, Emory University, Atlanta, GA 30333, USA</aff><author-notes><corresp id="cor1">*Madeline Y. Sutton: <email>msutton@cdc.gov</email></corresp><fn fn-type="other"><p>Academic Editor: W. T. Creasman</p></fn></author-notes><pub-date pub-type="ppub"><year>2013</year></pub-date><pub-date pub-type="epub"><day>19</day><month>12</month><year>2013</year></pub-date><volume>2013</volume><elocation-id>340309</elocation-id><history><date date-type="received"><day>24</day><month>7</month><year>2013</year></date><date date-type="rev-recd"><day>8</day><month>10</month><year>2013</year></date><date date-type="accepted"><day>22</day><month>10</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Kentaro Imai et al.</copyright-statement><copyright-year>2013</copyright-year><license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>More than half of persons living with HIV infection in the United States (U.S.) will be ≥50 years of age by 2020, including postmenopausal women. We conducted a systematic literature review about the effects of (1) HIV infection on age at menopause and (2) menopause on antiretroviral therapy (ART) response, in order to inform optimal treatment strategies for menopausal women living with HIV infection. We used the Ovid Medline database from 1980 to 2012. We included studies that focused on HIV-infected persons, included postmenopausal women, and reported outcome data for either age at menopause or response to ART across menopause. We identified six original research articles for age at menopause and five for response to ART across menopause. Our review revealed that current data were conflicting and inconclusive; more rigorous studies are needed. Disentangling the effects of menopause requires well-designed studies with adequate numbers of HIV-infected and HIV-uninfected women, especially disproportionately affected women of color. Future studies should follow women from premenopause through menopause, use both surveys and laboratory measurements for menopause diagnoses, and control for confounders related to normal aging processes, in order to inform optimal clinical management for menopausal women living with HIV.</p></abstract></article-meta></front><body><sec id="sec1"><title>1. Introduction</title><p>Globally, persons with human immunodeficiency virus (HIV) are living longer, healthier lives, due largely to the widespread use of effective highly active antiretroviral therapy (HAART) [<xref rid="B1" ref-type="bibr">1</xref>, <xref rid="B2" ref-type="bibr">2</xref>]. It is projected that by 2015–2020, half of persons living with HIV infection in the United States will be 50 years of age or older [<xref rid="B3" ref-type="bibr">3</xref>, <xref rid="B4" ref-type="bibr">4</xref>] and likely living with and managing other comorbid, chronic medical conditions that often accompany the aging process. These conditions include hypertension, diabetes, and for women, who make up half of all persons living with HIV infection worldwide, menopause [<xref rid="B5" ref-type="bibr">5</xref>]. For HIV-infected women taking effective ART, this longer survival translates into many women likely living beyond menopause well into their postmenopausal years. Yet large gaps exist in our understanding of the effect of HIV on the aging process for HIV-infected women as they approach and live through menopause. Prioritizing efforts to learn more about the potential impact of HIV on the lives of menopausal women are warranted in an effort to optimize care and treatment for older HIV-infected women.</p><p>In 2011, an estimated 25% of U.S. adults and adolescents living with HIV infection were women; many were near or already into their menopausal years (<xref ref-type="fig" rid="fig1">Figure 1</xref>) [<xref rid="B6" ref-type="bibr">6</xref>]. Substantial racial/ethnic disparities have been noted among women living with HIV infection across all age groups; among women living with and newly diagnosed with HIV infection in 2011, black/African Americans and Hispanics/Latinas were disproportionately represented (<xref ref-type="fig" rid="fig2">Figure 2</xref>) [<xref rid="B6" ref-type="bibr">6</xref>–<xref rid="B9" ref-type="bibr">9</xref>]. Understanding the effects of HIV on women and menopause could contribute to efforts to understand and close HIV-related racial/ethnic disparities.</p><p>To date, there have been inconsistent reports regarding several areas related to HIV-infected women and menopause. HIV-infected women were reported to lose ovarian function earlier in life than HIV-uninfected women, leading to an earlier onset of menopause among HIV-infected women [<xref rid="B10" ref-type="bibr">10</xref>]. Over the short term, a menopausal transition is associated with an altered mood state and sexual dysfunction, both of which can affect quality of life for women [<xref rid="B11" ref-type="bibr">11</xref>, <xref rid="B12" ref-type="bibr">12</xref>]. Over the long term, menopause accelerates the onset and progression of chronic diseases of aging, including cardiovascular disease, hypertension, diabetes, and reduced bone mineral density [<xref rid="B13" ref-type="bibr">13</xref>, <xref rid="B14" ref-type="bibr">14</xref>]. All of these risks suggest a possible increased burden of disease for HIV-infected women if they enter menopause at an earlier age and are living longer lives on effective ART treatment [<xref rid="B15" ref-type="bibr">15</xref>]. Our objectives were to conduct a systematic review of the literature to summarize data regarding: (1) age of menopause among women living with HIV infection, and (2) immunological and virological response to ART in HIV-infected menopausal women. Our goal was to identify research gaps, including questions regarding racial/ethnic disparities, and inform future initiatives to ensure optimal medical management for older HIV-infected women.</p></sec><sec id="sec2"><title>2. Methods</title><p>We conducted a literature search using the Ovid Medline database from 1980 to August 2012 to identify relevant articles. The search was limited to articles published in English that described studies of menopausal transition among HIV-infected humans. We focused on two topics: (1) age at menopause and (2) immunological and virological response to ART across menopause. We felt that understanding the age at which HIV-infected women went through menopause would provide important, informative context about their responses to ART, especially related to possible menopause-related symptoms/side effects; this information may be helpful to clinical providers who care for HIV-infected, older women. Search strategies used the keywords “HIV” and “menopause.” Additional search terms—added to yield the highest number of possible articles—included (1) for age at menopause, “age,” “aging,” “age at menopause,” “age of menopause,” “early,” and “early menopause” and (2) for response to ART across menopause, “antiretroviral” (ARV), “HAART,” “ART,” “ARV,” “treatment,” “response,” “response to ART,” “CD4,” and “viral load.” Final original research articles included (1) original research articles that studied age at menopause in HIV-infected women, and (2) original research articles that examined the difference in response to ART across menopause in HIV-infected women.</p><p>We also reviewed research articles using the same search terms as above that compared ART responses among HIV-infected men and women aged ≤40 years with age ≥55 years to supplement our review of ART response across menopause among HIV-infected women. Some studies documented a wide median age range (39–53 years) for menopause among women living with HIV [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>]. Most women have either entered or completed their menopausal transition by the age of 50 and almost all by the age of 55 [<xref rid="B19" ref-type="bibr">19</xref>]. HIV-infected women aged ≤40 years or aged ≥55 years may be characterized as premenopausal or postmenopausal, respectively, but documentation of menopausal status may vary depending on available clinical laboratory details reported in studies. Also, some studies have shown that immunological and virological response to ART do not differ by gender after adjusting for other factors, including age, race/ethnicity, and ART regimen [<xref rid="B20" ref-type="bibr">20</xref>–<xref rid="B24" ref-type="bibr">24</xref>].</p></sec><sec id="sec3"><title>3. Results</title><sec id="sec3.1"><title>3.1. Final Articles Included in Review</title><p>The process for article selection and exclusion is summarized in <xref ref-type="fig" rid="fig1">Figure 1</xref>. For age at menopause, 63 articles were identified, of which four were original research articles [<xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>] and 11 were review articles [<xref rid="B10" ref-type="bibr">10</xref>, <xref rid="B15" ref-type="bibr">15</xref>, <xref rid="B17" ref-type="bibr">17</xref>, <xref rid="B27" ref-type="bibr">27</xref>–<xref rid="B34" ref-type="bibr">34</xref>]. Forty-eight of 63 were excluded, because age at menopause in HIV-infected women was not discussed. In the 11 review articles, two more original research articles [<xref rid="B17" ref-type="bibr">17</xref>, <xref rid="B35" ref-type="bibr">35</xref>] that did not duplicate the four original research articles [<xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>] were identified, for a total of six original research articles [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>, <xref rid="B35" ref-type="bibr">35</xref>] for the review of age at menopause in HIV-infected women (<xref ref-type="fig" rid="fig3">Figure 3</xref>).</p><p>For ART response among HIV-infected persons, 54 articles were identified. Of those, a single original research article [<xref rid="B36" ref-type="bibr">36</xref>] and five review articles [<xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B28" ref-type="bibr">28</xref>, <xref rid="B34" ref-type="bibr">34</xref>, <xref rid="B37" ref-type="bibr">37</xref>, <xref rid="B38" ref-type="bibr">38</xref>] that reported response to ART in HIV-infected women were identified; 48 of 54 were excluded, because immunological response to ART in HIV-infected patients was not discussed. In the five review articles, 16 original research articles regarding response to ART in HIV-infected patients [<xref rid="B24" ref-type="bibr">24</xref>, <xref rid="B39" ref-type="bibr">39</xref>–<xref rid="B53" ref-type="bibr">53</xref>] were also reviewed as possible supplementary articles. Of these, four original research articles [<xref rid="B39" ref-type="bibr">39</xref>–<xref rid="B42" ref-type="bibr">42</xref>] that contained useful information about the two age groups of HIV-infected men and women (ages ≤40 years and ≥55 years) were selected as supplementary articles for the final review. Overall, one article that enrolled HIV-infected women only and four supplementary original research articles (five total) [<xref rid="B36" ref-type="bibr">36</xref>, <xref rid="B39" ref-type="bibr">39</xref>–<xref rid="B42" ref-type="bibr">42</xref>] were selected for the final review of response to ART among HIV-infected persons across menopause (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p></sec><sec id="sec3.2"><title>3.2. Age at Menopause</title><p>Age at menopause of HIV-infected women was reported in six studies [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>, <xref rid="B35" ref-type="bibr">35</xref>] (<xref ref-type="table" rid="tab1">Table 1</xref>). Four studies were conducted in the United States with racially and ethnically diverse groups of participants (consistent with the United States' epidemiology of HIV among women) [<xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B17" ref-type="bibr">17</xref>, <xref rid="B26" ref-type="bibr">26</xref>, <xref rid="B35" ref-type="bibr">35</xref>], one in Brazil [<xref rid="B25" ref-type="bibr">25</xref>] and one in France [<xref rid="B18" ref-type="bibr">18</xref>]. In four of the six studies, the authors assessed median age at menopause in describing age at menopause [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>]; the remaining two studies assessed mean age at menopause [<xref rid="B26" ref-type="bibr">26</xref>, <xref rid="B35" ref-type="bibr">35</xref>]. All six studies [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>, <xref rid="B35" ref-type="bibr">35</xref>] defined menopause as amenorrhea for 12 consecutive months [<xref rid="B54" ref-type="bibr">54</xref>].</p><p>Three of the six studies found no difference in age at menopause among HIV-infected [<xref rid="B17" ref-type="bibr">17</xref>, <xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B35" ref-type="bibr">35</xref>] and HIV-uninfected women [<xref rid="B36" ref-type="bibr">36</xref>]. Cejtin et al. found no significant difference in the mean age at menopause between HIV-infected and HIV-uninfected women in the Women Interagency HIV Study (WIHS): 47.7 and 48.0 years, respectively [<xref rid="B35" ref-type="bibr">35</xref>]. The WIHS study participants were demographically similar to those in a study by Fantry et al. [<xref rid="B17" ref-type="bibr">17</xref>], in terms of race/ethnicity, level of education, socioeconomic status, and drug use, all of which have been reported to influence age at menopause [<xref rid="B55" ref-type="bibr">55</xref>]. The median age at menopause for HIV-infected women was 50 years (IQR: 49–53) in the Fantry et al. study [<xref rid="B17" ref-type="bibr">17</xref>] and 49 years (IQR: 40–50) in a study by de Pommerol et al. [<xref rid="B18" ref-type="bibr">18</xref>], similar to what has been reported with large multiethnic population-based samples of HIV-uninfected women (median age for menopause = 50–52 years) in the United States [<xref rid="B56" ref-type="bibr">56</xref>, <xref rid="B57" ref-type="bibr">57</xref>] and Europe [<xref rid="B58" ref-type="bibr">58</xref>, <xref rid="B59" ref-type="bibr">59</xref>].</p><p>In contrast, the other three studies [<xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>] reported that menopause started at a younger age in HIV-infected women (<xref ref-type="table" rid="tab1">Table 1</xref>). A single cohort study by Schoembaum et al. reported a significant lower median age at menopause in HIV-infected women (46.0 years, IQR: 39.0–49.0), compared with HIV-uninfected women (47.0 years, IQR: 44.5–48.0, <italic>P</italic> = 0.03) [<xref rid="B16" ref-type="bibr">16</xref>]. In an analysis using multivariate logistic regression with adjustment for age, these authors demonstrated that HIV-infected women were 73% more likely to experience premature menopause compared with HIV-uninfected women (OR: 1.73, 95% confidence interval [CI]: 1.08–2.80, <italic>P</italic> = 0.024) [<xref rid="B16" ref-type="bibr">16</xref>]. Two other studies from Ferreira et al. and Clark et al. that included only HIV-infected women reported median ages at menopause of 47.5 years (IQR not provided) [<xref rid="B25" ref-type="bibr">25</xref>] and 47 years (IQR: 32.0–57.0), respectively [<xref rid="B26" ref-type="bibr">26</xref>].</p><p>In one study included in this review, de Pommerol et al. examined premature menopause (onset before age 40 years) and reported that 12% of postmenopausal HIV-infected women sampled had experienced premature menopause [<xref rid="B18" ref-type="bibr">18</xref>]. This prevalence of premature menopause among HIV-infected women was higher than the reported prevalence of 1.1–6.3% among women in the general population of HIV-uninfected women enrolled in the American Study of Women's Health Across the Nation cohort, although the sampled populations were different demographically [<xref rid="B60" ref-type="bibr">60</xref>, <xref rid="B61" ref-type="bibr">61</xref>]. Other reports have noted comparable mean ages at menopause between HIV-infected and HIV-uninfected women but found a disproportionate number of HIV-infected women with a younger median age for menopause [<xref rid="B62" ref-type="bibr">62</xref>, <xref rid="B63" ref-type="bibr">63</xref>].</p><p>Three studies examined the association of CD4 cell count with age at menopause [<xref rid="B18" ref-type="bibr">18</xref>–<xref rid="B20" ref-type="bibr">20</xref>]. Schoembaum et al. reported that a CD4 cell counts of >500 cells/mm<sup>3</sup> (OR: 0.19, 95% CI: 0.08–0.48, <italic>P</italic> = 0.001) and 200–500 cells/mm<sup>3</sup> (OR: 0.35, 95% CI: 0.15–0.81, <italic>P</italic> = 0.015) was independently associated with a decreased risk of premature menopause compared with a CD4 cell count <200 cells/mm<sup>3</sup> [<xref rid="B16" ref-type="bibr">16</xref>]. The median age of menopause was 42.5 years in HIV-infected women with CD4 cell counts of <200 cells/mm<sup>3</sup>, while the median age of menopause was 46.0 years in those with CD4 cell counts of 200–500 cells/mm<sup>3</sup> and 46.5 years in those with CD4 cell counts of >500 cells/mm<sup>3</sup> (<italic>P</italic> = 0.009) [<xref rid="B16" ref-type="bibr">16</xref>]. de Pommerol et al. reported that a CD4 cell count of <200 cells/mm<sup>3</sup> at enrollment was also associated with an earlier onset of menopause, compared with a CD4 cell count of >350 cells/mm<sup>3</sup> (HR: 2.25, 95% CI: 0.94–5.39, <italic>P</italic> = 0.069) [<xref rid="B18" ref-type="bibr">18</xref>]. Fantry et al. also showed no significant association between lower CD4 cell count and onset of menopause [<xref rid="B17" ref-type="bibr">17</xref>].</p><p>Although the same definition was used for menopause for all six studies, each used different methods for documenting age at menopause, and all evaluated menopause at a single time point [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>, <xref rid="B35" ref-type="bibr">35</xref>]. Evaluating the presence of menopause at only one time point could have led to an overestimation of its prevalence. Only the Cejtin et al. study [<xref rid="B35" ref-type="bibr">35</xref>] measured menopause using laboratory biologic markers, including follicle stimulating hormone (for diagnosing menopause, in addition to self-reported menopausal status, multiple consistently elevated serum FSH levels are useful as a laboratory marker [<xref rid="B17" ref-type="bibr">17</xref>] and can help distinguish menopause from other causes of amenorrhea [<xref rid="B54" ref-type="bibr">54</xref>, <xref rid="B65" ref-type="bibr">64</xref>].) in addition to the women's self-report of amenorrhea (FSH). The other five studies [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>] used only self-reported questionnaire data to document age at menopause and did not confirm menopause biologically. Thus, age at menopause reported in the five studies [<xref rid="B16" ref-type="bibr">16</xref>–<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B25" ref-type="bibr">25</xref>, <xref rid="B26" ref-type="bibr">26</xref>] could be different from the age when the women actually experienced menopause, as no laboratory verifications were obtained and misdiagnoses of menopause in HIV-infected women were possible.</p></sec><sec id="sec3.3"><title>3.3. Immunological and Virological Response to ART across Menopause</title><p>To evaluate response to ART in HIV-infected women and men, we reviewed studies that examined changes in CD4 cell counts (immunological response) and plasma HIV RNA viral loads (virological response) after initiation of ART [<xref rid="B21" ref-type="bibr">21</xref>, <xref rid="B36" ref-type="bibr">36</xref>, <xref rid="B39" ref-type="bibr">39</xref>, <xref rid="B40" ref-type="bibr">40</xref>, <xref rid="B44" ref-type="bibr">44</xref>, <xref rid="B49" ref-type="bibr">49</xref>–<xref rid="B51" ref-type="bibr">51</xref>]. We identified only one study that examined response to ART in HIV-infected women with well-characterized menopause [<xref rid="B36" ref-type="bibr">36</xref>]. This study (<xref ref-type="table" rid="tab2">Table 2</xref>) included 267 HIV-infected racially and ethnically diverse women (220 premenopausal and 47 postmenopausal) and demonstrated that the median change in absolute CD4 cell counts and percentages did not differ between pre-menopausal and post-menopausal women after two years of ART (260 versus 273 cells/mm<sup>3</sup>, <italic>P</italic> = 0.51; 11.0% versus 12.0%, <italic>P</italic> = 0.79) [<xref rid="B36" ref-type="bibr">36</xref>]. There were also no differences between pre-menopausal and post-menopausal women in the proportions achieving plasma HIV RNA viral loads <50 copies/mL after two years of HAART (75% versus 77%, <italic>P</italic> > 0.99; OR: 0.82, 95% CI: 0.36–1.89) [<xref rid="B36" ref-type="bibr">36</xref>]. These data suggest that both pre- and post-menopausal HIV-infected women compared with uninfected women respond equally well to ART during at least the first two years after initiation.</p><p>We also identified four supplementary original research articles regarding ART response among both men and women living with HIV infection (<xref ref-type="table" rid="tab3">Table 3</xref>) [<xref rid="B39" ref-type="bibr">39</xref>–<xref rid="B42" ref-type="bibr">42</xref>]. Two studies [<xref rid="B41" ref-type="bibr">41</xref>, <xref rid="B42" ref-type="bibr">42</xref>] included only ART-naïve HIV-infected men and women in the pre-menopausal and post-menopausal age ranges, whereas the two other studies [<xref rid="B39" ref-type="bibr">39</xref>, <xref rid="B40" ref-type="bibr">40</xref>] included some ART-experienced patients. Three of the four supplementary articles analyzed data from European cohorts [<xref rid="B39" ref-type="bibr">39</xref>–<xref rid="B41" ref-type="bibr">41</xref>]. The fourth used data from the United States and Canada (North American AIDS Cohort Collaboration on Research and Design) and consisted of 83% male patients [<xref rid="B42" ref-type="bibr">42</xref>].</p><p>Regarding immunological response to ART, Manfredi and Chiodo found that both men and women aged ≥55 years who started ART had a significantly smaller increase in mean CD4 cell counts compared with persons aged ≤35 years (77 versus 114 cells/mm<sup>3</sup>, <italic>P</italic> = 0.0001) [<xref rid="B39" ref-type="bibr">39</xref>]. However, Knobel et al. and Althoff et al. concluded that there was no significant difference in immunological response between HIV-infected men or women comparing persons age ≤40 years with persons age ≥60 years [<xref rid="B40" ref-type="bibr">40</xref>, <xref rid="B42" ref-type="bibr">42</xref>]. Finally, the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) study showed that HIV-infected men and women combined aged 55–59 years had a similar immunological response to ART compared with persons aged 30–39 years (HR: 0.97, 95% CI: 0.92–1.03, <italic>P</italic> = 0.31) [<xref rid="B41" ref-type="bibr">41</xref>]. However, HIV-infected women aged ≥60 years in the COHERE study were 7% less likely to experience immunological response compared with women aged 30–39 years (HR: 0.93, 95% CI: 0.87–0.98, <italic>P</italic> < 0.001) [<xref rid="B41" ref-type="bibr">41</xref>].</p><p>Regarding virological response to ART, both the Manfredi et al. and Knobel et al. studies reported that HIV-infected men and women aged ≤35 years [<xref rid="B39" ref-type="bibr">39</xref>] or aged ≤40 years [<xref rid="B40" ref-type="bibr">40</xref>] had no significant difference in either the decrease in mean plasma HIV RNA viral load or the number of patients achieving <50 copies/mL, compared with those aged ≥55 or aged ≥60, respectively (<xref ref-type="table" rid="tab3">Table 3</xref>) [<xref rid="B39" ref-type="bibr">39</xref>, <xref rid="B40" ref-type="bibr">40</xref>]; these studies were limited by small sample sizes. However, the COHERE study (>49,900 participants) showed that the probability of virological response was 24% higher in patients aged 55–59 years than those aged 30–39 years (HR: 1.24, 95% CI: 1.17–1.32, <italic>P</italic> < 0.001) [<xref rid="B41" ref-type="bibr">41</xref>]. In contrast, Althoff (>12,000 participants) showed that the hazard of achieving <500 copies/mL of HIV viral loads within two years after ART initiation in HIV-infected patients aged ≥60 years was 26% less than that in patients aged 18–29 years [<xref rid="B42" ref-type="bibr">42</xref>].</p><p>Overall, the outcomes of the four supplemental studies [<xref rid="B39" ref-type="bibr">39</xref>–<xref rid="B42" ref-type="bibr">42</xref>] were conflicting. Possible reasons include having used different age categories for comparison, variation in study sample size, and lack of data for women only. Moreover, none of the four studies, which sampled both men and women with HIV infection, stratified data by sex, and menopause status to permit comparison with the Patterson et al. study [<xref rid="B36" ref-type="bibr">36</xref>], which consisted solely of women. The number of men was significantly greater than that of women for studies in <xref ref-type="table" rid="tab3">Table 3</xref> and could have affected study outcomes. Some studies, not included in our review because data on menopause were not reported, suggest that immunological and/or virological responses to ART differ by gender and among all age groups after adjusting for other factors [<xref rid="B22" ref-type="bibr">22</xref>, <xref rid="B66" ref-type="bibr">65</xref>, <xref rid="B67" ref-type="bibr">66</xref>].</p></sec></sec><sec id="sec4"><title>4. Discussion</title><p>Our review revealed that current data on age at menopause and the effect of menopause on the response to ART for HIV-infected women are conflicting. Part of the challenge is that existing studies have not adequately distinguished the unique contribution, if any, of HIV infection or its consequences such as lower CD4 cell count [<xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B18" ref-type="bibr">18</xref>], from the contribution of other risk factors for early menopause irregular menses [<xref rid="B15" ref-type="bibr">15</xref>], such as drug use [<xref rid="B18" ref-type="bibr">18</xref>], tobacco smoking [<xref rid="B68" ref-type="bibr">67</xref>], black/African American race [<xref rid="B18" ref-type="bibr">18</xref>], fewer years of education [<xref rid="B16" ref-type="bibr">16</xref>, <xref rid="B57" ref-type="bibr">57</xref>], and lower body mass index (BMI) [<xref rid="B54" ref-type="bibr">54</xref>, <xref rid="B59" ref-type="bibr">59</xref>], all of which are common among persons living with HIV infection. Many current reports have been limited to cohorts of HIV-infected persons only [<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B56" ref-type="bibr">56</xref>, <xref rid="B59" ref-type="bibr">59</xref>, <xref rid="B69" ref-type="bibr">68</xref>–<xref rid="B71" ref-type="bibr">70</xref>]. In addition, some conflicting data (in studies with small sample sizes) suggest that in contrast to women in the general population, age at menopause among HIV-infected women may not be associated with current smoking [<xref rid="B16" ref-type="bibr">16</xref>], ethnicity [<xref rid="B16" ref-type="bibr">16</xref>], or fewer years of education [<xref rid="B18" ref-type="bibr">18</xref>, <xref rid="B54" ref-type="bibr">54</xref>]. Additionally, although women with more advanced HIV infection and potentially lower BMI or wasting may be more likely to have amenorrhea, the association between BMI and the onset of menopause is inconsistent [<xref rid="B56" ref-type="bibr">56</xref>, <xref rid="B72" ref-type="bibr">71</xref>] or absent [<xref rid="B59" ref-type="bibr">59</xref>] in the limited number of studies of HIV-infected women that have examined this association.</p><p>Also, more consistency regarding the definition of menopause, including FSH biological measurements, is warranted for future studies, because not all amenorrhea is menopause. Menopause is usually defined as the cessation of menses (amenorrhea) in women for ≥12 consecutive months with symptoms suggestive of menopause and in which other causes of amenorrhea have been ruled out and/or the FSH level is elevated. Amenorrhea, which is defined as missing menstrual periods for at least three consecutive months [<xref rid="B63" ref-type="bibr">63</xref>], has been reported commonly among HIV-infected women and has been attributed to wasting [<xref rid="B73" ref-type="bibr">72</xref>] or anovulation [<xref rid="B74" ref-type="bibr">73</xref>]. Cejtin et al. reported that HIV infection was significantly associated with prolonged amenorrhea from causes other than menopause (OR: 3.16, 95% CI: 1.26–7.95, <italic>P</italic> = 0.02) when adjusted for age [<xref rid="B54" ref-type="bibr">54</xref>]. Cejtin et al. reported that only 74.6% of HIV-infected women who were age 45 years or older and had prolonged amenorrhea were truly menopausal [<xref rid="B54" ref-type="bibr">54</xref>], while nearly 90% of HIV-uninfected women agedd ≥45 years with prolonged amenorrhea were truly menopausal [<xref rid="B75" ref-type="bibr">74</xref>]. Presence of menses may also be affected by use of ART; ART was significantly associated with having higher serum FSH among HIV-infected women compared with uninfected women (<italic>P</italic> < 0.05) [<xref rid="B16" ref-type="bibr">16</xref>]. Use of ART (HR: 0.48, 95% CI: 0.32–0.71, <italic>P</italic> = 0.003) and higher CD4 cell counts (<italic>P</italic> = 0.007) have been linked to a lower incidence of amenorrhea [<xref rid="B76" ref-type="bibr">75</xref>]. HIV-infected women who have HIV-related hypothalamic amenorrhea, especially those taking ART, may experience a return of menses once CD4 cell counts increase [<xref rid="B76" ref-type="bibr">75</xref>].</p><p>Menopause results in decreased ovarian synthesis of estrogen; estrogen and progesterone can effect HIV replication in peripheral blood mononuclear cells [<xref rid="B77" ref-type="bibr">76</xref>]. In animals, estrogen deficiency reduces the percentage of T cells in bone marrow [<xref rid="B78" ref-type="bibr">77</xref>]. Among HIV-uninfected women, post-menopausal women have lower CD4 cell counts than pre-menopausal women [<xref rid="B79" ref-type="bibr">78</xref>]. Estrogen deficiency associated with menopause and normal reduction in thymic tissue that accompanies aging [<xref rid="B80" ref-type="bibr">79</xref>] could affect CD4 cell recovery and HIV replication. Thus, post-menopausal women may respond differently to ART compared with pre-menopausal women.</p><p>Regarding the effect of menopause on ART response, we were unable to compare the Patterson et al. study [<xref rid="B36" ref-type="bibr">36</xref>] to any other report, because no other studies were conducted with only HIV-infected women. Although it is difficult to disentangle the effect of aging on response to ART, we assessed data from the supplementary articles (both women and men) in order to compensate for the paucity of specific data (women only) of the effect of menopause on response to ART. Data from the supplementary articles were inconsistent. Some data suggest that younger persons experience better immunological and/or virological responses to ART [<xref rid="B44" ref-type="bibr">44</xref>, <xref rid="B50" ref-type="bibr">50</xref>, <xref rid="B52" ref-type="bibr">52</xref>]. The COHERE study showed that immunological response to ART was similar in the patients aged 55–59 years but poorer in those aged ≥60 years, compared with the patients who were younger than the average age at menopause [<xref rid="B41" ref-type="bibr">41</xref>]. This finding may imply that the effects of aging on CD4 cell count recovery are multifactorial, resulting from both normal age-related immunosenescence and by the negative effects of estrogen deficiency that occurs with menopause [<xref rid="B81" ref-type="bibr">80</xref>, <xref rid="B82" ref-type="bibr">81</xref>]. If a low CD4 cell count increases risk of early menopause, then the effects of HIV infection and menopause would be compounded; earlier diagnosis of HIV and initiating ART treatment before CD4 cells are <200 cells/mm<sup>3</sup> would be warranted for women approaching menopause.</p></sec><sec id="sec5"><title>5. Conclusion/Recommendations for Next Steps</title><p>Understanding the effects of HIV infection on age at menopause and on response to ART is important for ensuring the best possible care for the expanding cohort of women living with HIV who approach and live through menopause and are taking ART. This information may also help inform clinicians and researchers to assess whether ART for middle-aged women with HIV infection should be modified across menopause. Advanced HIV infection is a known independent risk factor for early mortality as well as both cardiovascular disease and decreased bone mineral density. Earlier onset of menopause is also associated with increased mortality [<xref rid="B83" ref-type="bibr">82</xref>, <xref rid="B84" ref-type="bibr">83</xref>] and both decreased bone mineral density [<xref rid="B85" ref-type="bibr">84</xref>] and cardiovascular disease [<xref rid="B86" ref-type="bibr">85</xref>].</p><p>Our review highlights research deficits in our understanding of the effects of HIV infection on age at menopause and opportunities for future work. Ideally, studies of menopause in HIV-infected women should include sufficient numbers of women, both HIV-infected and HIV-uninfected, who are representative of the racially and ethnically diverse women living with or at risk of HIV infection in the United States. Such studies should follow women across menopause and capture data on the growing number of factors recognized to be related to age of menopause, including race/ethnicity, tobacco smoking, drug use, level of education, BMI, use of ART, CD4 cell counts, and HIV viral loads. Furthermore, a combination of questionnaires and laboratory measurement of serum FSH levels will improve classification of menopause in women, especially HIV-infected women for whom amenorrhea is highly prevalent. Additional data may also be helpful for clinicians managing HIV-infected women with chronic medical conditions that also disproportionately affect older black/African American and Hispanic/Latina women of color, such as diabetes and hypertension [<xref rid="B87" ref-type="bibr">86</xref>, <xref rid="B88" ref-type="bibr">87</xref>].</p><p>Today, over 30 years since HIV was first identified, the number of women living with HIV infection, taking ART, and living longer and healthier lives is expanding. Epidemiological studies of older, menopausal women living with HIV infection are needed to address questions raised as this epidemiologic landscape changes. Such studies will provide important data that will help to optimize care for the growing numbers of post-menopausal women living with HIV infection.</p></sec></body><back><ack><title>Disclaimer</title><p>The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.</p></ack><ack><title>Conflict of Interests</title><p>The authors have no conflict of interests relevant to this paper.</p></ack><ref-list><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Porter</surname><given-names>K</given-names></name></person-group><article-title>Determinants of survival following HIV-1 seroconversion after the introduction of HAART</article-title><source><italic>The Lancet</italic></source><year>2003</year><volume>362</volume><issue>9392</issue><fpage>1267</fpage><lpage>1274</lpage><pub-id pub-id-type="other">2-s2.0-0142186280</pub-id></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hacker</surname><given-names>MA</given-names></name><name><surname>Petersen</surname><given-names>ML</given-names></name><name><surname>Enriquez</surname><given-names>M</given-names></name><name><surname>Bastos</surname><given-names>FI</given-names></name></person-group><article-title>Highly active antiretroviral therapy in Brazil: the challenge of universal access in a context of social inequality</article-title><source><italic>Revista Panamericana de Salud Publica/Pan American Journal of Public Health</italic></source><year>2004</year><volume>16</volume><issue>2</issue><fpage>78</fpage><lpage>83</lpage><pub-id pub-id-type="other">2-s2.0-4544381959</pub-id><pub-id pub-id-type="pmid">15357932</pub-id></element-citation></ref><ref id="B3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>High</surname><given-names>KP</given-names></name><name><surname>Brennan-Ing</surname><given-names>M</given-names></name><name><surname>Clifford</surname><given-names>DB</given-names></name><etal></etal></person-group><article-title>HIV and aging: state of knowledge and areas of critical need for research. 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Estimates were calculated based on data provided in [<xref rid="B6" ref-type="bibr">6</xref>].</p></caption><graphic xlink:href="OGI2013-340309.002"></graphic></fig><fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Flowchart of article selection and exclusion for the systematic review: HIV and menopause, 1980–2012.</p></caption><graphic xlink:href="OGI2013-340309.003"></graphic></fig><table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Studies available through 2012 evaluating age at menopause in HIV-infected women.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Authors<break></break>(year)</th><th align="center" rowspan="1" colspan="1">Country</th><th align="center" rowspan="1" colspan="1">Number of women for analysis</th><th align="center" rowspan="1" colspan="1">Percent of participants who were black/African American or Hispanic/Latina</th><th align="center" rowspan="1" colspan="1">HIV status</th><th align="center" rowspan="1" colspan="1"><italic>N</italic></th><th align="center" rowspan="1" colspan="1">Number of women with menopause</th><th align="center" rowspan="1" colspan="1">Age at onset of menopause (years)</th><th align="center" rowspan="1" colspan="1"><italic>P</italic> value</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Clark et al. (2000) [<xref rid="B26" ref-type="bibr">26</xref>]</td><td align="center" rowspan="1" colspan="1">United States</td><td align="center" rowspan="1" colspan="1">52</td><td align="center" rowspan="1" colspan="1">43% (black/AA)<break></break>15% (Hispanic)</td><td align="center" rowspan="1" colspan="1">Infected<break></break>Uninfected</td><td align="center" rowspan="1" colspan="1">52<break></break>0</td><td align="center" rowspan="1" colspan="1">26 (50.0%)<break></break>NA</td><td align="center" rowspan="1" colspan="1">47 (IQR 32–57) (mean)<break></break>NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="left" rowspan="1" colspan="1">Cejtin et al. (2004) [<xref rid="B35" ref-type="bibr">35</xref>]</td><td align="center" rowspan="1" colspan="1">United States</td><td align="center" rowspan="1" colspan="1">1335</td><td align="center" rowspan="1" colspan="1">NR</td><td align="center" rowspan="1" colspan="1">Infected<break></break>Uninfected</td><td align="center" rowspan="1" colspan="1">1063<break></break>272</td><td align="center" rowspan="1" colspan="1">NR<break></break>NR</td><td align="center" rowspan="1" colspan="1">47.7 (mean)<break></break>48.0</td><td align="center" rowspan="1" colspan="1">NS</td></tr><tr><td align="left" rowspan="1" colspan="1">Fantry et al. (2005) [<xref rid="B17" ref-type="bibr">17</xref>]</td><td align="center" rowspan="1" colspan="1">United States</td><td align="center" rowspan="1" colspan="1">120</td><td align="center" rowspan="1" colspan="1">95% (black/AA)</td><td align="center" rowspan="1" colspan="1">Infected<break></break>Uninfected</td><td align="center" rowspan="1" colspan="1">120<break></break>0</td><td align="center" rowspan="1" colspan="1">NR<break></break>NA</td><td align="center" rowspan="1" colspan="1">50.0 (IQR 49.3–53.0) (median)<break></break>NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr><tr><td align="left" rowspan="1" colspan="1">Schoenbaum et al. (2005) [<xref rid="B16" ref-type="bibr">16</xref>]</td><td align="center" rowspan="1" colspan="1">United States</td><td align="center" rowspan="1" colspan="1">571</td><td align="center" rowspan="1" colspan="1">49% (black/AA)<break></break>40% (Hispanic)</td><td align="center" rowspan="1" colspan="1">Infected<break></break>Uninfected</td><td align="center" rowspan="1" colspan="1">302<break></break>269</td><td align="center" rowspan="1" colspan="1">62 (20.5%)<break></break>40 (14.9%)</td><td align="center" rowspan="1" colspan="1">46.0 (IQR 39.0–49.0)<break></break>47.0 (IQR 44.5–48.0)</td><td align="center" rowspan="1" colspan="1">0.03</td></tr><tr><td align="left" rowspan="1" colspan="1">Ferreira et al. (2007) [<xref rid="B25" ref-type="bibr">25</xref>]</td><td align="center" rowspan="1" colspan="1">Brazil</td><td align="center" rowspan="1" colspan="1">251</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">Infected<break></break>Uninfected</td><td align="center" rowspan="1" colspan="1">96<break></break>155</td><td align="center" rowspan="1" colspan="1">NR<break></break>NR</td><td align="center" rowspan="1" colspan="1">47.5 (median)<break></break>NR</td><td align="center" rowspan="1" colspan="1">NR</td></tr><tr><td align="left" rowspan="1" colspan="1">de Pommerol et al. (2011) [<xref rid="B18" ref-type="bibr">18</xref>]</td><td align="center" rowspan="1" colspan="1">France</td><td align="center" rowspan="1" colspan="1">404</td><td align="center" rowspan="1" colspan="1">NA</td><td align="center" rowspan="1" colspan="1">Infected<break></break>Uninfected</td><td align="center" rowspan="1" colspan="1">404<break></break>0</td><td align="center" rowspan="1" colspan="1">69 (17.1%)<break></break>NA<break></break></td><td align="center" rowspan="1" colspan="1">49 (IQR 40–50) (median)<break></break>NA</td><td align="center" rowspan="1" colspan="1">NA</td></tr></tbody></table><table-wrap-foot><fn><p>AA: African American, IQR: interquartile range, NA: not applicable, NR: not reported, NS: not significant.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tab2" orientation="portrait" position="float"><label>Table 2</label><caption><p>Studies available through 2012 evaluating response to ART across menopause in HIV-infected women.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1">Authors <break></break>(year)</th><th align="center" rowspan="2" colspan="1">Study design<break></break>(followup)</th><th align="center" rowspan="2" colspan="1">Menopause status</th><th align="center" rowspan="2" colspan="1">Number of women (total sample; <italic>n</italic> = 267)</th><th align="center" rowspan="2" colspan="1">Percent of total participants who were black/African American or Hispanic/Latina</th><th align="center" colspan="3" rowspan="1">CD4 cell counts in women after ART</th><th align="center" colspan="3" rowspan="1">HIV viral loads in women after ART</th></tr><tr><th align="center" rowspan="1" colspan="1">Measure</th><th align="center" rowspan="1" colspan="1">Results</th><th align="center" rowspan="1" colspan="1"><italic>P</italic> value</th><th align="center" rowspan="1" colspan="1">Measure</th><th align="center" rowspan="1" colspan="1">Results</th><th align="center" rowspan="1" colspan="1"><italic>P</italic> value</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Patterson et al. (2009) [<xref rid="B36" ref-type="bibr">36</xref>]</td><td align="center" rowspan="1" colspan="1">Cohort<break></break>(2 years)</td><td align="center" rowspan="1" colspan="1">Pre<break></break>Post</td><td align="center" rowspan="1" colspan="1">220<break></break>47</td><td align="center" rowspan="1" colspan="1">61% (black/AA)<break></break>17% (Hispanic)</td><td align="center" rowspan="1" colspan="1">Increase in median CD4 from baseline</td><td align="center" rowspan="1" colspan="1">260 (11.0%)<break></break>273 (12.0%)</td><td align="center" rowspan="1" colspan="1">0.51</td><td align="center" rowspan="1" colspan="1">Women achieving <50 copies/mL </td><td align="center" rowspan="1" colspan="1">75%<break></break>77%</td><td align="center" rowspan="1" colspan="1">>0.99</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Odds ratio of achieving <50 copies/mL for premenopausal women</td><td align="center" rowspan="1" colspan="1">0.82<break></break>(0.36–1.89)</td><td align="center" rowspan="1" colspan="1">NS</td></tr></tbody></table><table-wrap-foot><fn><p>AA: African American, NS: not significant, Pre: premenopausal, Post: postmenopausal.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tab3" orientation="portrait" position="float"><label>Table 3</label><caption><p>Supplemental list of studies evaluating response to ART in HIV-infected persons (men and women), through 2012.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1">Authors <break></break>(year)</th><th align="center" rowspan="2" colspan="1">Study design<break></break> (followup)</th><th align="center" rowspan="2" colspan="1">Age groups<break></break> (years)</th><th align="center" rowspan="2" colspan="1">Number of patients</th><th align="center" rowspan="2" colspan="1">Number of <break></break>women</th><th align="center" colspan="3" rowspan="1">CD4 cell counts in persons after initiating ART</th><th align="center" colspan="3" rowspan="1">HIV viral loads in persons after ART</th></tr><tr><th align="center" rowspan="1" colspan="1">Measure</th><th align="center" rowspan="1" colspan="1">Results</th><th align="center" rowspan="1" colspan="1"><italic>P</italic> value</th><th align="center" rowspan="1" colspan="1">Measure</th><th align="center" rowspan="1" colspan="1">Results</th><th align="center" rowspan="1" colspan="1"><italic>P</italic> value</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Manfredi and Chiodo (2000) [<xref rid="B39" ref-type="bibr">39</xref>]</td><td align="center" rowspan="1" colspan="1">Case-control <break></break>(1 year)</td><td align="center" rowspan="1" colspan="1">≤35 <break></break>≥55 </td><td align="center" rowspan="1" colspan="1">84<break></break>21</td><td align="center" rowspan="1" colspan="1">29 (34.5%)<break></break>8 (38.1%)</td><td align="center" rowspan="1" colspan="1">Patients with CD4 increase ≤20 cells/mm<sup>3</sup> or ≤10% from baseline (12-month followup)</td><td align="center" rowspan="1" colspan="1">4 (4.8%)<break></break>5 (23.8%)</td><td align="center" rowspan="1" colspan="1">0.02</td><td align="center" rowspan="1" colspan="1">Decrease in mean viral load (copies/mL)</td><td align="center" rowspan="1" colspan="1">31,225 (98.7%) <break></break>49,325 (98.4%)</td><td align="center" rowspan="1" colspan="1">NS</td></tr><tr><td align="left" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1"> </td><td align="center" rowspan="1" colspan="1">Increase in mean CD4 from baseline (% of increase) (12-month followup) </td><td align="center" rowspan="1" colspan="1">114 (49.4%)<break></break>77 (36.3%)</td><td align="center" rowspan="1" colspan="1">0.0001</td><td align="center" rowspan="1" colspan="1">Patients achieving <50</td><td align="center" rowspan="1" colspan="1">62 (73.8%)<break></break>15 (71.4%)</td><td align="center" rowspan="1" colspan="1">NS</td></tr><tr><td align="left" rowspan="1" colspan="1">Knobel et al. (2001) [<xref rid="B40" ref-type="bibr">40</xref>]</td><td align="center" rowspan="1" colspan="1">Cohort<break></break>(2 years)</td><td align="center" rowspan="1" colspan="1">≤40 <break></break>≥60</td><td align="center" rowspan="1" colspan="1">671<break></break>28</td><td align="center" rowspan="1" colspan="1">219 (32.6%)<break></break>9 (32.1%)</td><td align="center" rowspan="1" colspan="1">Increase in mean CD4 from baseline (24-month followup) </td><td align="center" rowspan="1" colspan="1">196 (SD 100)<break></break>228 (SD 145)</td><td align="center" rowspan="1" colspan="1">NS</td><td align="center" rowspan="1" colspan="1">Patients achieving <50</td><td align="center" rowspan="1" colspan="1">342 (50.9%)<break></break>19 (66.7%)</td><td align="center" rowspan="1" colspan="1">NS</td></tr><tr><td align="left" rowspan="1" colspan="1">COHERE Study, Sabin (2008) [<xref rid="B41" ref-type="bibr">41</xref>]</td><td align="center" rowspan="1" colspan="1">Cohort <break></break>(5 years)</td><td align="center" rowspan="1" colspan="1">30–39 <break></break>55–59 <break></break>≥60 <break></break>All ages</td><td align="center" rowspan="1" colspan="1">22,410<break></break>1,656<break></break>1,613<break></break>49,921</td><td align="center" rowspan="1" colspan="1">6239 (27.8%)<break></break>303 (18.3%)<break></break>320 (19.8%)</td><td align="center" rowspan="1" colspan="1">HR of immunological response (defined as CD4 increase of >100 cells/<italic>μ</italic>L) </td><td align="center" rowspan="1" colspan="1">REF<break></break>0.97 (0.92–1.03)<break></break>0.93 (0.87–0.98)</td><td align="center" rowspan="1" colspan="1">0.31<break></break><0.001</td><td align="center" rowspan="1" colspan="1">HR of virological response (defined as HIV RNA <50 copies/mL)</td><td align="center" rowspan="1" colspan="1">REF<break></break>1.24 (1.17–1.32)<break></break>1.18 (1.12–1.26)</td><td align="center" rowspan="1" colspan="1"><0.001<break></break><0.001</td></tr><tr><td align="left" rowspan="1" colspan="1">Althoff et al. (2010) [<xref rid="B42" ref-type="bibr">42</xref>]</td><td align="center" rowspan="1" colspan="1">Cohort<break></break>(2 years)</td><td align="center" rowspan="1" colspan="1">18–29 <break></break>30–39 <break></break>≥60 <break></break>All ages</td><td align="center" rowspan="1" colspan="1">1,342<break></break>3,930<break></break>598<break></break>12,196</td><td align="center" rowspan="1" colspan="1">320 (24.8%)<break></break>767 (19.5%)<break></break>50 (8.4%)</td><td align="center" rowspan="1" colspan="1">HR of CD4 increase of at least 100 cells/mm<sup>3</sup> within 2 years of ART initiation</td><td align="center" rowspan="1" colspan="1">REF<break></break>0.71 (0.89–1.05)<break></break>1.05 (0.92–1.20)</td><td align="center" rowspan="1" colspan="1">NR</td><td align="center" rowspan="1" colspan="1">HR of achieving <500 copies/mL within 2 years of ART initiation</td><td align="center" rowspan="1" colspan="1">REF<break></break>0.92 (0.85–1.00)<break></break>0.74 (0.65–0.85)</td><td align="center" rowspan="1" colspan="1">NR</td></tr></tbody></table><table-wrap-foot><fn><p>ART: antiretroviral treatment, HR: hazard ratio, NR: not reported, NS: not significant, REF: referent, yrs: years.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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