PICO 4 Should antiretroviral therapy (ART) be offered to HIV-infected partners in serodiscordant...

download PICO 4 Should antiretroviral therapy (ART) be offered to HIV-infected partners in serodiscordant couples to reduce HIV transmission to uninfected partners?

of 28

  • date post

    04-Jan-2016
  • Category

    Documents

  • view

    214
  • download

    0

Embed Size (px)

Transcript of PICO 4 Should antiretroviral therapy (ART) be offered to HIV-infected partners in serodiscordant...

  • PICO 4 Should antiretroviral therapy (ART) be offered to HIV-infected partners in serodiscordant couples to reduce HIV transmission to uninfected partners?

    PICO 5Should ART be started earlier than clinically indicated for the HIV-infected individuals in serodiscordant partnerships to reduce HIV transmission to uninfected partners?

    George W. Rutherford, M.D.Cochrane HIV/AIDS Group, University of California, San Francisco, USA WHO consultant

  • SearchesPrincipal investigators of ongoing trials have been contactedDatabases (01 Jan 1987 01 Dec 2010) PubMed EMBASE Cochrane CENTRAL Web of Science LILACS Also searched grey literature

    (PICO 4 and PICO 5)

    Total of records1814Duplicates removed331Records screened1483Records excluded1458Full-text articles obtained25Studies included in review7

  • PICO 4 frameworkP opulation Serodiscordant couples (heterosexual)I ntervention ART for the HIV-infected partnerC omparison No ART for the HIV-infected partnerO utcomes

    Q4: Should ART be offered to HIV-infected partners in serodiscordant couples to reduce HIV transmission to uninfected partners?

    Incident HIV infection in the previously uninfected partnerAcquisition of primary drug-resistant HIV by previously HIV-uninfected partnerAdverse events and side effects of ARTHIV-related mortalityHIV-related morbidityQuality of life (both partners)

  • Outcomes: PICO 4

    OutcomesRelative importance( rank 19 most critical)CommentHIV incidence9CriticalHIV incidence (sensitivity)9CriticalAcquisition of primary drug-resistant HIV by previously HIV-negative partner 9CriticalAdverse events / side-effects of ART8CriticalHIV-related mortality8CriticalHIV-related morbidity7ImportantQuality of life7Important

  • Summary of studies

    Author, yearPopulationFindings Del Romero 2010Heterosexual couples attending a clinic in Madrid, Spain from 1989 to 2008 648 couples analyzed (ART) Incident HIV infection (overall) Rate ratio 0.21 (95% CI 0.01-3.75) Incident HIV infection (index partners CD4 < 200) Risk ratio 0.16 (95% CI 0.01-2.59) Incident HIV infection (index partners CD4 200-350) Risk ratio 0.10 (95% CI 0.01-1.26) Incident HIV infection (index partners CD4 350) Risk ratio 0.17 (95% CI 0.01-2.92)

    Donnell 2010Heterosexual African adults who were positive for both HIV and HSV in Botswana, Kenya, Rwanda, South Africa, Tanzania, Uganda, and Zambia 3,408 couples analyzed (ART) Incident HIV infection (overall) Rate ratio 0.08 (95% CI 0.01-0.57) Incident HIV infection (index partners CD4 < 200) Rate ratio 0.00 (95% CI 0.00-0.04) Incident HIV infection (index partners CD4 200-350) Rate ratio 0.65 (95% CI 0.10-4.35) Incident HIV infection (index partners CD4 350) Rate ratio 0.00 (95% CI 0.00-0.15)

  • Summary of studies (continued)

    Author, yearPopulationFindings Melo 2008Heterosexual discordant couples 93 couples studied (ART) Incident HIV infection (overall) Rate ratio 0.10 (95% CI 0.01-1.67) Incident HIV infection (index partners CD4 < 200) Risk ratio 0.30 (95% CI 0.01-6.28) Incident HIV infection (index partners CD4 200-350) Risk ratio 0.33 (95% CI 0.02-5.76)

    Musicco 1994A cohort of heterosexual couples in Italy in which men where infected and women were uninfected 436 monogamous couples recruited from 16 centers in Italy (AZT monotherapy) AZT main exposure Incident HIV infection (overall) Rate Ratio 0.88 (95% CI 0.36-2.16)

    Reynolds 2009An observational cohort of HIV discordant couples in Rakai, Uganda 193 couples analyzed (ART) Incident HIV infection (overall) Rate ratio 0.23 (95% CI 0.01-3.83)

  • Summary of studies (continued)

    Author, yearPopulationFindings Sullivan 2009Heterosexual discordant couples in Rwanda and Zambia followed from 2002-2008 2993 couples studied (ART)Incident HIV infection (overall) Rate ratio 0.21 (95% CI 0.08-0.56)

    Wang 2010A cohort of heterosexual couples testing and seeking treatment at county hospitals in China in 2006 to 20081927 heterosexual couples studied (ART)Incident HIV infection (overall) Risk ratio 1.44 (95% CI 0.88-2.44)

  • GRADE evidence profile

    Author(s): Anglemyer, Andrew; Kennedy, Gail, Rutherford, GeorgeDate: 2010-12-22Question: Should ART be offered to HIV-positive partners in serodiscordant couples to reduce HIV transmission to HIV-negative partners?Settings: Spain, Africa, Brazil, Italy, and China Bibliography: Del Romero 2010; Donnell 2010; Melo 2008; Reynolds 2009; Sullivan 2009; Wang 2010; Musicco 1994

    Quality assessment

    Summary of Findings

    No. of patients

    Effect

    No. of studies

    Design

    Limitations

    Inconsistency

    Indirectness

    Imprecision

    Other considerations

    Antiretroviral Therapy

    control

    Relative effect (95% CI)

    Absolute effect

    Quality

    Importance

    HIV Incidence

    7

    observational studies

    no serious limitations

    no serious inconsistency

    no serious indirectness

    no serious imprecision

    strong association1

    77/1869 (4.1%)2,3

    355/4809 (7.4%)2,3

    Rate Ratio 0.37 (0.14 to 0.97)

    47 fewer per 1000 (from 2 fewer to 63 fewer)

    MODERATE

    CRITICAL

    HIV Incidence (Sensitivity)

    5

    observational studies

    serious4

    no serious inconsistency

    no serious indirectness

    no serious imprecision

    very strong association5

    5/759 (0.7%)2,3

    316/1409 (22.4%)2,3

    Rate Ratio 0.17 (0.08 to 0.37)

    186 fewer per 1000 (from 141 fewer to 206 fewer)

    MODERATE

    CRITICAL

    1 Rate Ratio < 0.502 Less than 5% of sample was imputed due to missing information in the denominator.3 Numerators and Denominators taken from text where possible. Numbers were not used to calculate the relative effect estimates.4 Two studies were removed due to differences in intervention or incomplete data.5 RR < 0.20

  • GRADE evidence profile

    Author(s): Anglemyer, Andrew; Kennedy, Gail, Rutherford, GeorgeDate: 2010-12-22Question: Should ART be offered to HIV-positive partners in serodiscordant couples to reduce HIV transmission to HIV-negative partners?Settings: Spain, Africa, Brazil, Italy, and China Bibliography: N/A

    Quality assessment

    Summary of Findings

    No. of patients

    Effect

    No. of studies

    Design

    Limitations

    Inconsistency

    Indirectness

    Imprecision

    Other considerations

    Antiretroviral Therapy

    control

    Relative effect (95% CI)

    Absolute effect

    Quality

    Importance

    HIV-related mortality

    --

    Not measured

    CRITICAL

    Acquisition of primary drug-resistant HIV by previously HIV-negative partner

    --

    Not measured

    CRITICAL

    Adverse events and side-effects of ART

    --

    Not measured

    CRITICAL

    HIV-related morbidity

    --

    Not measured

    IMPORTANT

    Quality of life

    --

    Not measured

    IMPORTANT

  • Quality of evidence: PICO 4Moderate quality evidence: Estimate of effect is somewhat certain

    Rated down for study limitations and precision issues.Rated up for strong associations. No studies explored impact of ART on many critical or important outcomes

  • Risk assessment:PICO 4Del Romero 2010: Genitourinary infections occurred in 8 (5.6%) of 144 treated couples during follow up and in 62 (16.0%) of 388 untreated couples. Wang 2010: Of 1369 treated couples, 266 (19.4%) switched259 (97.4%) of these switched due to an adverse event3 other patients developed resistance

  • Risk-benefit table

    FactorExplanation / EvidenceJudgmentQuality of EvidenceStrong evidence from six of seven observational studies of a benefitThere is no definitive RCT completed; a large one (HPTN052) is in the field and will be until 2015.Moderate. An estimate of effect is somewhat certain.Balance of Benefits vs. Harms There is moderate quality evidence suggests that 2-63 fewer infections would occur per 1000 couples who received ART. If two outlier studies (Musicco and Wang) are excluded (sensitivity analysis) 141-206 fewer infections would occur per 1000 couples who received ART. No studies explored the impact of ART among serodiscordant couples on the following adverse outcomes: Acquisition of primary drug resistant HIV by uninfected partner Adverse events and side effects of ART HIV-related mortality HIV-related morbidity Quality of life.Benefits may outweigh harms, but rigorous RCTs and large observational studies of adverse events among serodiscordant couples are needed.

  • Risk-benefit table (continued)

    Values and preferencesThere is a feeling of optimism that new possibilities are emerging for HIV-positive people to live with less anxiety about infecting negative partners, and with more hope for healthy conception and childbirth options. Providers of HTC for couples must be well-informed about all of the options involving treatment for prevention so that couples can understand the implications and be free to make fully informed choices about these fundamental aspects of their lives. At the same time, care must be taken to ensure that no one is pressured to take an approach to HIV prevention that they are not comfortable with. These are personal and joint decisions. Supportive if choices are fully informedCost and feasibilityAppropriate in settings where ART is regularly provided

    Generally conforms to national and international guidelinesNot a major issue

  • Proposed recommendationStatement: Antiretroviral therapy should be offered to HIV-infected partners in serodiscordant couples to reduce HIV transmission to uninfected partners.

    Overall grade of recommendation: Direction: For / Against