What is the benefit of the biomedical and behavioral interventions in preventing HIV transmission?

Kuchenbecker, Ricardo

doi:10.1590/1809-4503201500050004

ABSTRACT

Introduction:

Scientific evidence supports the sinergy between biomedical and behavioral interventions aimed at preventing the transmission of HIV as a strategy to eradicate AIDS.

Objective:

To characterize comparatively the benefits from biomedical and behavioral interventions to prevent HIV transmission.

Methods:

Narrative review. We performed a comparative analysis of the benefits of studied interventions by means of estimating the number needed to treat (NNT). Evaluated interventions: counseling activities for behavior change to prevent exposure to HIV; antiretroviral pre-exposure prophylaxis (PrEP) and antiretroviral post-exposure prophylasis (PEP) for HIV and treatment of serodiscordant couples as a strategy for prevention of HIV transmission (TasP).

Results:

counseling interventions and TasP have smaller NNTs, equal to, respectively, 11 (95%CI 9 - 18) at 12 months and 34 (95%CI 23 - 54) in 42 months comparatively to PrEP interventions, that resulted in 41 (95%CI 28 - 67) individuals receiving antiretrovirals in order to prevent one case of HIV infection at 36 months for men and serodiscordant couples. PEP interventions are associated with protective effects estimated at 81%. Lack of trials evaluating PEP prevents estimate of NNT.

Conclusion:

The estimate of the NNT can be a helpful parameter in the comparison between the effectiveness of different behavioral and biomedical HIV prevention strategies. Studies evaluating the benefit and safety of combined behavioral and biomedical interventions are needed, especially considering the attributable fraction of each component. Integration of behavioral and biomedical interventions is required to achieve complete suppression of the virus, and thus reducing viral replication, infectivity and the number of cases.

Keywords:
Anti-retroviral agents; Acquired immunodeficiency syndrome; HIV; Sexually transmitted diseases; Pre-exposure prophylaxis; Post-exposure prophylaxis; Circumcision, male; Therapeutics; Behavior; Disease prevention

[1] Corresponding author: Ricardo Kuchenbecker. Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2.350, CEP: 90035-903, Porto Alegre, RS, Brasil. E-mail: rsk@hcpa.edu.br

Objective	Population studied	Intervention	Measure of association and impact RR, OR, ARR and NNT (95%CI)
U.S. Preventive Services Task Force. Behavioral counseling for sexual risk reduction aimed at preventing STD/HIV in primary care in 2014⁸.
To assess the benefits and risks of sexual counseling strategies in order to reduce risk for STIs/HIV infection	Systematic review of 31 RCTs (n = 70,324) comprising predominantly African-American female adolescents and adults, in primary care clinics and STD/HIV services	"Low intensity" interventions Up to 0.5 hour of duration "Moderate intensity" interventions Between 0.5 and 2 hours of duration "High intensity" interventions" Over 2 hours of duration	STD/HIV infections in adolescents in 12 months: "Low" and "medium intensity" interventions No difference between groups "High intensity" interventions OR = 0.38 (95%CI 0.24 - 0.60) NNT = 11 (95%CI 9 - 18) with cumulative incidence of 15% per year. STD/HIV infections in adults in 12 months: "Low intensity" interventions OR = 0.85 (95%CI 0.66 - 1.10) "Medium intensity" interventions OR = 0.88 (95%CI 0.66 - 1.04) "High intensity" interventions OR = 0.70 (95%CI 0.56 - 0.87) NNT = 25 (95%CI 17 59), with cumulative incidence of 15% per year.
Eaton L et al. Meta-analysis of behavioral interventions in single counseling sessions for STD/HIV prevention in 2012¹³.
To assess whether interventions for risk reduction of exposure to HIV and other STDs based on single educational sessions reduce the occurrence of STD/HIV	52,465 people in 20 RCTs and observational studies	Behavioral strategies to reduce incidence of STD/HIV from a single counseling session aimed at reducing behaviors related to HIV exposure. Did not included interventions involving counseling and HIV testing	STD/HIV occurrence OR = 0.65 (95%CI 0.55 - 0.77) Condom use OR = 0.22 (95%CI 0.06 - 0.37)
Objective	Population studied	Intervention	Measure of association and impact RR, OR, ARR and NNT (95%CI)
Fonner et al. Systematic review on voluntary counseling and testing for changing HIV-related risk in developing countries¹⁴.
Systematically review the literature examining the effectiveness of testing and voluntary counseling strategies in changing HIV-related behaviors in developing countries	40,309 individuals evaluated in one RCT and several observational studies	Systematic review and meta-analysis involving studies conducted in low and middle income countries: Sub-Saharan Africa, Zimbabwe, Uganda, Zambia, Mozambique and Kenya	Reduction in number of sexual partners OR = 0.69 (95%CI 0.53 - 0.90) Increased frequency of condom use OR = 1.39 (95%CI 0.97 - 1.99) Increased frequency of condom use among HIV-positive individuals OR = 3.24 (95%CI 2.29 - 4.58) There were no differences in the incidence of HIV and STD/HIV between participants who received voluntary counseling associated with HIV testing and those who did not receive such strategy
Study: effectiveness of counseling for risk reduction in transmission of HIV and STDs. RESPECT Study, 1998⁹.
To compare the effects of two interactive counseling interventions for STD/HIV prevention with educational messages	5,758 seronegative individuals	Group 1: Extended counseling + 4 interactive sessions at 3 - 4 week intervals (200 minutes total) Group 2: Brief counseling + 2 interactive sessions at 7 - 10 day intervals (40 minutes total) Group 3: Two educational messages given at 7 - 10 days Group 4: Two educational messages at 7 - 10 days without follow-up by the end of the study	STD/HIV infections in 6 months: Extended counseling (group 1) RR = 0.69 (95%CI 0.54 - 0.88) NNT = 32 (95%CI 19 - 91) Brief counseling (group 2) RR = 0.72 (95%CI 0.56 - 0.91) NNT = 35 (95%CI 20 - 116) STD/HIV infections in 12 months: Extended counseling (group 1) RR = 0.78 (95%CI 0.65 - 0.95) NNT = 32 (95%CI 18 - 146) Brief counseling (group 2) RR = 0.79 (95%CI 0.68 - 0.98) NNT = 38 (95%CI 19 - 527)
Objective	Population studied	Intervention	Measure of association and impact (RR, OR and NNT (95%CI))
Relative effectiveness of counseling for HIV prevention with rapid and conventional tests. Randomized clinical trial. RESPECT 2 Study, 2005¹⁰.			Measure of association and impact (RR, OR and NNT (95%CI))
To compare the effectiveness of counseling and testing using rapid HIV testing, in a single visit, with counseling and testing with standard test, conducted in two visits	3,281 seronegative individuals	Standard counseling: One 40-minute session + conventional HIV test (two visits) Brief counseling: One 30-minute session + rapid HIV test (one visit)	STD/HIV infections in 12 months: Brief counseling (group 2) RR = 1.1 (95%CI 0.96 - 1.29) STD/HIV infections in 12 months among men who have sex with men: Brief counseling (group 2) RR = 1.86 (95%CI 0.92 - 3.76) STD/HIV infections in individuals without STD/HIV history: Brief counseling RR = 1.21 (95%CI 0.99 - 1.48)
Effect of counseling with rapid testing in reducing the risk of STD/HIV infection. AWARE Study, 2013¹¹.
To evaluate the effect of brief counseling strategies centered on the patient at the moment of rapid HIV testing on the risk of subsequent STD/HIV infection	5,012 patients from nine American DST clinics	Counseling group: Risk reduction strategies based on the patient, recommendations used in the RESPECT 2 Study, followed by rapid testing Control group: Rapid test accompanied by verbal information corresponding to the test procedure itself, its interpretation and information about the test's "window" period	STD/HIV infections in 6 months: ARR = 1.12 (95%CI 0.94 - 1.33) STD/HIV infections in six months among MSM: ARR = 1.41 (95%CI 1.05 - 1.90) STD/HIV infections in six months among women: ARR = 1.07 (95%CI 0.79 - 1.43) STD/HIV infections in six months among MSW: ARR = 0.81 (95%CI 0.50 - 1.31)

Objective	Population studied	Intervention	Relative reduction of incidence (95%CI)	Blood detection of prophylaxis among seroconverted patients	Protective factor (%) and safety	NNT (95%CI)
Sexual post-exposure prophylaxis (PEP).
Cardo D et al. Case and control studies on seroconversion among healthcare workers after percutaneous exposure, 1997¹⁷.
To identify risk factors for HIV transmission in health care workers after percutaneous exposure to blood infected with the virus	Health professionals: 33 cases and 665 controls	-	OR = 0.19 (95%CI 0.06 - 0.52)	-	81%	-
Irvine C et al. Systematic review on the effectiveness of PEP in studies with animal models (primates)¹⁵.
To evaluate the efficacy of PEP in animal models (primates)	Primates (n = 28 studies, 408 primates)	Different PEP strategies involving multiple ARVs&	OR = 0.11 (95%CI 0.05 - 0.23)	-	89%	-
Sexual pre-exposure prophylaxis (PrEP).
Partners PrEP Study, 2012²⁹.
To evaluate the efficacy and safety of TDF or TDF/FTC versus placebo as a strategy for prevention of HIV-1 infection among HIV-1 serodiscordant men and women couples	4,747 heterosexual men and women with known seropositive partner (serodiscordant couples)	Daily oral intake of TDF versus daily oral intake of TDF/FTC versus placebo	TDF: 67% (95%CI 44 - 81) TDF/FTC: 75% (95%CI 55 - 87)	81%	86% (TDF), 90% (TDF/FTC) in patients with detectable TDF No major EAD differences	Daily TDF: NNT = 46 (95%CI 30 - 83) TDF/FTC: NNT = 41 (95%CI 28 - 67) in 36 months
TDF2 Study, 2012³³.
To evaluate the efficacy and safety of TDF/FTC versus placebo in preventing HIV infection among sexually active heterosexual adults	1,219 heterosexual men and women	Daily oral intake of TDF/FTC versus placebo	TDF/FTC: 63% (95%CI 22 - 83)	79%	78% TDF/FTC higher frequency of nausea, vomiting and dizziness	NNT = 41 (95%CI 22 - 154) in 1.1 years
iPrEX Study, 2010³¹.
To evaluate the efficacy and safety of the daily oral intake of TDF/FTC compared to placebo in preventing HIV infection among men and transgender women who have sex with men	2,499 MSM and transvestites	Daily oral intake of TDF/FTC versus placebo	TDF/FTC: 44% (95%CI 15 - 63)	51%	92% in participants with detectable TDF or FTC; 99% with TDF concentrations with daily use	NNT 45 (95%CI 26 - 140) in 1.8 years
FEM-PrEP Study, 2012³⁴.
To evaluate the efficacy and safety of the daily oral intake of TDF/FTC compared to placebo in preventing HIV infection among women	2,120 women	Daily oral intake of TDF/FTC versus placebo	TDF/FTC 6% (95%CI 52 - 41). No statistically significant reduction in HIV incidence	35 to 38% in a single visit	Very low frequency in PrEP use. TDF/FTC group reported nausea and vomiting rates and higher liver transaminases than the control group	Study interrupted
Bangkok TDF Study, 2013³⁵.
To evaluate the efficacy and safety of the daily oral intake of TDF versus placebo in preventing HIV infection among injectable drug users	2,413 IDU	TDF versus placebo	TDF 48.9% (95%CI 9.6 - 72.2)	NA	Nausea and vomiting more frequent in the TDF Group. Similar frequency of severe EAD in both groups
Antiretroviral treatment of HIV infection as prevention (TasP).
Study on the prevention of infection by HIV-1 with early antiretroviral therapy. HPTN052, 2011⁴⁰.
To compare early-start with late-start antiretroviral therapy in HIV-infected patients in stable sexual relationships with seronegative partners	1,763 heterosexual and homosexual serodiscordant couples	Early-start versus late-start antiretroviral therapy	HIV incidence: 0.1% per 100 persons-year versus 1.7% per 100 persons-year.	-	96% (95%CI 73 - 99)	NNT 34 (95%CI 23 - 54) in 42 months

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