Title: When to start ART: >350 cells/mm

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Title: When to start ART: >350 cells/mm³ - community with HIV

Contents

1. PICO question ... 1

2. Search strategy ... 1

3. Flow diagram of screening process ... 2

4. Study descriptions ... 2

5. Bibliography of included studies ... 4

6. Excluded studies with reasons ... 5

1. PICO question

When to start ART: treatment as prevention, >350 cells/mm³, community with HIV P 1) Adults and adolescents with HIV, 2) female sex workers with HIV, 3) men who have sex

with men with HIV, 4) people who inject drugs with HIV

I ART initiation at CD4 >350 cells/mm³ or irrespective of CD4 cell count

C Defer ART initiation until CD4 cell count ≤350 cells/mm³ or symptomatic HIV disease (WHO stages 3 and 4)

O Community-level incidence and prevalence, morbidity and mortality, non-HIV morbidity, non- HIV mortality, adherence, retention, HIV drug resistant, severe adverse events, TB incidence 2. Search strategy

01 Jan 1996 – 24 Aug 2012 Search Query

#5 Search (((#1) AND #2) AND #3) AND #4

#4 Search (start*[tiab] OR initia*[tiab] OR begin*[tiab] OR timing[tiab] OR early[tiab] OR earli*[tiab] OR (CD4[tiab] AND (irrespective[tiab] OR “above 350”[tiab] OR ≥350[tiab]

OR >350[tiab]))

#3 Search HAART[tiab] OR ART[tiab] OR antiretroviral[tiab] OR anti-retroviral[tiab] OR

"Antiretroviral Therapy, Highly Active"[Mesh] OR "Anti-Retroviral Agents"[Mesh]

#2 Search randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [MeSH] OR random allocation [MeSH] OR double-blind method [MeSH]

OR single-blind method [MeSH] OR clinical trial [pt] OR clinical trials [MeSH] OR ("clinical trial" [tiab]) OR ((singl* [tiab] OR doubl* [tiab] OR trebl* [tiab] OR tripl* [tiab]) AND (mask* [tiab] OR blind* [tiab])) OR (placebos [MeSH] OR placebo* [tiab] OR random*

[tiab] OR research design [mh:noexp] OR follow-up studies [MeSH] OR prospective studies [MeSH] OR control*[tiab] OR prospectiv* [tiab]) OR non-randomi*[tiab] OR before after study[tiab] OR time series[tiab] OR case control[tiab] OR prospective cohort[tiab] OR cohort*[tiab] OR cross-section*[tiab] OR prospective[tiab] OR retrospective[tiab] OR research design[mh:noexp] OR follow-up studies[MeSH] OR prospective studies[MeSH] OR control*[tiab] OR prospectiv*[tiab]) NOT (animals [MeSH] NOT human [MeSH])

#1 Search "HIV Infections"[MeSH] OR HIV[MeSH] OR HIV[tiab] OR hiv-1*[tiab] OR hiv- 2*[tiab] OR hiv1[tiab] OR hiv2[tiab] OR HIV infect*[tiab] OR human immunodeficiency

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Search Query

virus[tiab] OR human immunedeficiency virus[tiab] OR human immuno-deficiency

virus[tiab] OR human immune-deficiency virus[tiab] OR ((human immun*) AND (deficiency virus[tiab])) OR acquired immunodeficiency syndrome[tiab] OR acquired immunedeficiency syndrome[tiab] OR acquired immuno-deficiency syndrome[tiab] OR acquired immunedeficiency syndrome[tiab] OR ((acquired immun*) AND (deficiency syndrome[tiab]))

3. Flow diagram of screening process

(individual-level outcomes and community-level outcomes)

4. Study descriptions

When to start ART: treatment as prevention, >350 cells/mm³, community with HIV

Estimating the impact of ART initiation at CD4 >350 cells/mm³ compared to deferring initiation on the community level requires comparing communities. In one community, the patients would be treated at CD4 >350 cells/mm³ and, in another, the patients are treated at ≤350 cells/mm³. Alternatively, we could look at only one community as a pre versus post design if a study had data on treatment initiation at ≤350 cells/mm³ in previous years (pre) and, in latter years, treatment initiation at >350 cells/mm³ (post). This type of study, if it were done deliberately as an intervention, would provide direct evidence. However, when practice changes gradually and is not the result of a particular intervention, studies reporting these results could suffer from ecological fallacy.

1055 records identified through database searching

854 records screened

58 full-text articles assessed for eligibility

Studies included in review Individual: 24 Community: 14

201 duplicates removed

816 total records excluded

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Castel 2012: There are no data on treatment. The study reports changes in mean viral load over time.

Cowan 2012: This is an ecological study that examined the proportion of all men who have sex with men with viral loads >500 copies/ml. They present data from the pre-highly active antirerotiviral therapy (HAART) era and from the post-HAART era. They present community-level viral load and treatment coverage data but not CD4 data.

Das 2010: This is also an ecological study that presents trends in community viral load in San Francisco, USA, over time. There are no data presented on treatment, so examining the effect of early treatment versus deferred treatment is not possible.

Fang 2004: This is a modelling study based on data from an ecological study. It provides data on the incidence of HIV over time in the pre-HAART and post-HAART eras. This analysis, unfortunately, does not address the PICO question.

Hogg 2012: This is an ecological study that presents trends in HIV diagnoses (not incidence) over time in various regions in Canada. The authors showed that, for every 1% increase in ART use in a province, the odds ratio for reducing the new HIV diagnoses was 1.08. No data are presented on CD4 count or viral load.

Kamwi 2012: This is a modelling paper describing the potential effects of diagnosing and treatment strategies in Namibia. Currently, the country guidelines dictate treatment initiation when CD4 falls below 350 cells/mm³. If these guidelines were changed to initiate ART when CD4 falls below 500 cells/mm³ (coverage of at least 95%), the investigators calculate that there would be 4890 deaths averted, 14 000 infections averted and 25 000 life-years gained by 2025. If the treatment guidelines were to change from

<350 to <500 cells/mm³ (coverage of at least 95%) and coverage of 50% of those with CD4 >500

cells/mm³, 6820 deaths would be averted, 27 000 infections would be averted and 37 000 life-years would be gained by 2025.

Katz 2002: This is an ecological study performed in San Francisco, USA, exploring the trends in high- risk sexual behaviour, HIV incidence and ART uptake among men who have sex with men. The use of HAART increased among men who have sex with men with AIDS, as did also the proportion of men who have sex with men reporting unsafe sexual practices. In addition, the annual HIV incidence rate increased, suggesting that any benefit from HAART in risk per sexual contact was offset by general increases in sexual risk. There was no report on immune status among treated men who have sex with men.

Law 2011: The authors assess the calendar trends in detectable viral load in among people with HIV receiving ART in Australia. The observed detectable viral load among people receiving ART decreased to 5.3% by 2009. The authors also predicted viral load based on multivariate models and found that they declined over time. This study did not consider immune status at treatment initiation.

Manavi 2012: This is an ecological study in the United Kingdom showing trends in viral load over time.

The authors do not report any data on treatment.

Montaner 2010: This is an ecological study that shows trends in baseline CD4 count before ART initiation over time. The authors show that the number of individuals using ART increased while the number of newly reported HIV infections fell over time. For every 100 additional individuals receiving

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ART, the number of new HIV cases decreased by a factor of 0.97 (not considering immune status). And for every 1 log10 decrease in viral load, the number of new HIV cases decreased by a factor of 0.86. ART initiation at specific immune status levels was assessed through the median CD4 cell count at baseline for the entire population. The median CD4 cell count pre-ART initiation ranged from a high of 310 cells/mm³ in 1997 to a low of 150 cells/mm³ in 2003.

Montaner 2012: This is an update of Montaner 2010 that adds 2010 and 2011 data. The median CD4 cell count pre-HAART was the highest in 2011 at 360 cells/mm³, which means that 50% of the patients in 2011 had pre-ART CD4 below this. We could potentially compare 2011 community viral load data to other years, but this would assume that the pre-HAART CD4 count of all people with HIV was over 350 cells/mm³ (and we know that only approximately 50% have pre-ART CD4 counts >350 cells/mm³) and similarly that the CD4 cell counts of all people with HIV before 2011 were <350 cells/mm³ (and we know that at least some of them had CD4 counts ≥350 cells/mm³). These assumptions would likely be

misleading.

Porco 2004: This is a probabilistic risk model of HIV seroincidence and high-risk sexual behaviour over time based on 534 men who have sex with men. Assuming a constant prevalence of HIV infection, HIV infectivity decreased from 0.120 before widespread use of ART to 0.048 after widespread ART use. Their modelling and results do not consider the immune status of the population.

Wood 2009: This is a prospective cohort design of people who inject drugs in Vancouver, Canada. The authors estimated community plasma viral load in the six months before negative tests and future incidence. There were 622 people who inject drugs with HIV and 1429 people who inject drugs without HIV evaluated. Among HIV-uninfected people who inject drugs, Cox models adjusting for high-risk sexual activities suggested that community viral load was independently related to the time to HIV seroconversion (hazard ratio=3.32 per log10 increase). Essentially, this study suggests that, as community viral load increases, so does the risk that people who inject drugs will acquire HIV infection. There is no discussion about immune status at treatment initiation.

5. Bibliography of included studies

1. Castel AD, Befus M, Willis S, Griffin A, West T, Hader S, Greenberg AE. Use of the community viral load as a population-based biomarker of HIV burden. AIDS 2012; 26: 345–353.

2. Cowan SA, Gerstoft J, Haff J, Christiansen AH, Nielsen J, Obel N. Stable incidence of HIV diagnoses among Danish men who have sex with men despite increased engagement in unsafe sex. J Acquir Immune Defic Syndr. 2012 Sep 1;61(1):106-11.

3. Das M, Chu PL, Santos G-M, Scheer S, Vittinghoff E, McFarland W, Colfax GN. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco.

PLoS ONE 2010; 5(6): e11068.

4. Fang C-T, Hsu H-M, Twu S-J, Chen M-Y, Chang Y-Y, Hwang J-S, Wang J-D, Chuang C-Y, Division of AIDS and STD, Center for Disease Control, Department of Health, Executive Yuan.

Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. J Infect Dis 2004; 190: 879-85.

5. Hogg RS, Lima VD, Wood E, Kerr T, Harrigan R, Shannon K, Montaner JSG. HAART-related decrease in the rate of new HIV diagnoses – a unique trend. British Columbia, Canada [Abstract 1115]. 19th Annual Conference on Retroviruses and Opportunistic Infections. Seattle,

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Washington, March 5-8, 2012.

6. Kamwi R, Hamunime N, Odiit M, Gweshe J, Muadinohamba A, Shihepo E, Van Renterghem H, Jonas A, De Klerk M, Mahy M, Forster N, Kahuure K. Treatment as prevention in a country with high ART coverage: the Namibia example [Abstract MOPDC01-4]. XIX International AIDS Conference, Washington, DC, July 23, 2012.

7. Katz MH, Schwarcz SK, Kellogg TA, Klausner JD, Dilley JW, et al. Impact of highly active antiretroviral treatment on HIV seroincidence among men who have sex with men: San Francisco.

Am J Public Health 2002; 92: 388–394.

8. Law MG, Woolley I, Templeton DJ, Roth N, Chuah J, et al. Trends in detectable viral load by calendar year in the Australian HIV observational database. J Int AIDS Soc 2011; 14: 10.

9. ManaviK, MartinK, SmitE, Hawker J.Community viral load counts and new HIV-positive patients in Birmingham, United Kingdom, between 2006 and 2011 [Abstract TUPE213]. XIX International AIDS Conference, Washington, DC, July 24, 2012.

10. Montaner JS, Lima VD, Barrios R, Yip B, Wood E, Kerr T, Shannon K, Harrigan PR, Hogg RS, Daly P, Kendall P. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study.

Lancet 2010; 376:532-39.

11. Montaner J, Lima VD, Yip B, Day I, Gustafson R, Barrios R, Kerr T, Wood E, Harrigan R, Brunham R, Krajden M, Gilbert M, Ogilvie G, Hogg R, Nakagawa B, Daly P, Kendall P.

Expanded HAART coverage is associated with decreased HIV/AIDS morbidity and new HIV diagnoses: an update on the “treatment as prevention” experience in British Columbia, Canada [Abstract THPE103]. XIX International AIDS Conference, Washington, DC, July 26, 2012.

12. Porco TC, Martin JN, Page-Shafer KA, Cheng A, Charlebois E, Grant RM, Osmond DH. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS 2004;

18: 81–88.

13. Tanser F, Bärnighausen T, Grapsa E, Newell M-L. Effect of ART coverage on rate of new HIV infections in a hyper-endemic, rural population: South Africa. 19th Conference andRetroviruses and Opportunistic Infections (CROI), Paper #136LB. March 5-8, 2012; Seattle, Washington, USA.

14. Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, Harrigan R, Montaner JSG. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. Br Med J 2009; 338:b1649.

6. Excluded studies with reasons

Reason for exclusion from GRADE analyses: commentary or not an acceptable study design 1 Castel AD, Befus M, Willis S, Griffin A,

West T, Hader S, Greenberg AE. Use of the community viral load as a population- based biomarker of HIV burden. AIDS.

2012;26(3):345-53.

Study design: Ecological analyses using surveillance data

Population and setting: 15 467 HIV cases alive from 2004 to 2008 in Washington, DC, USA.

Intervention: No intervention (ecological study).

Comparator: No comparator (ecological study).

Results: Community viral load (CVL) significantly decreased over time (P < 0.0001) with a mean CVL 33 847 copies/ml in 2008. The proportion with

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Reason for exclusion from GRADE analyses: commentary or not an acceptable study design

undetectable viral load increased from 15.4% to 57.4%

of cases. The highest mean and total viral load and lowest proportions of undetectable viral loads were found among black men and women. The highest mean and total CVLs, and the worst socioeconomic indicators, were clustered around predominantly African-American, impoverished neighbourhoods, which also have some of the highest HIV prevalence rates in the city.

Conclusions: Mean and total CVL are important indicators for understanding characteristics of a population’s viral burden and HIV epidemic and for assessing changes and trends over time.

2 Cowan SA, Gerstoft J, Haff J, Christiansen AH, Nielsen J, Obel N. Stable incidence of HIV diagnoses among Danish men who have sex with men despite increased engagement in unsafe sex. J Acquir Immune Defic Syndr. 2012;61(1):106-11.

Study design: Ecological analysis using registry data.

Population and setting: 1035 (1995) to 1813 (2010) HIV-positive men who have sex with men in Denmark from 1995 to 2010.

Results: Number with detectable viral lead (VL) (defined as >400 copies/ml) decreased 75% from 1035 to 262, and the cohort community reproductive rate decreased from 0.099 to 0.071.

Conclusions: Despite reported unsafe sex increasing among men who have sex with men in this population, HIV incidence has remained stable for almost a decade with detectable VL decreasing and the cohort

community reproductive rate decreasing.

3 Das M, Chu PL, Santos GM, Scheer S, Vittinghoff E, McFarland W, Colfax GN.

Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PLoS One.

2010;5(6):e11068.

Study design: Ecological analysis using surveillance data.

Population and setting: 12 512 HIV-positive people from San Francisco, CA, USA with at least one VL measurement during the study period of 2004 to 2008.

Intervention: No intervention (ecological study)

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Reason for exclusion from GRADE analyses: commentary or not an acceptable study design Comparator: No comparator (ecological study) Results: New HIV diagnoses creased from 798 in 2004 to 434 in 2008. The overall mean CVL for the study period was 23 348 copies/ml, but the mean CVL significantly decreased over time (P = 0.003), as did the total CVL (P = 0.002).

Conclusions: Decreases in CVL were associated with new HIV diagnoses, and CVL could be used as important outcome to track the epidemic, allocate resources and evaluate the effectiveness of HIV prevention and treatment efforts.

4 Fang CT, Hsu HM, Twu SJ, Chen MY, Chang YY, Hwang JS, Wang JD, Chuang CY; Division of AIDS and STD, Center for Disease Control, Department of Health, Executive Yuan. Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. J Infect Dis

2004;190(5):879-85.

Study design: Ecological analysis using surveillance data

Population and setting: HIV-positive cases from 1984 to 2002 in Taiwan (n=4390 HIV-positive cases in 2002).

Intervention: No intervention (ecological study) Comparator: No comparator (ecological study) Results: Comparing the pre-ART and post-ART eras, after implementing free ART the rate of HIV

transmission decreased by 53% from 0.391 to 0.184 new cases/prevalence case-years from 1984 to 2002.

Conclusions: Access to free ART significantly decreased the number of new HIV infections and directly contributed to the control of the epidemic in Taiwan.

5 Hogg RS, Lima VD, Wood E, Kerr T, Harigan R, Shannon K, Montaner JSG.

HAART-related decrease in the rate of new HIV diagnoses – a unique trend: British Columbia, Canada. Abstract presentation at CROI 2012.

Study design: Ecological study using surveillance data.

Population and setting: New HIV diagnoses in Canada from 1995 to 2009.

Results: A total of 36 977 people were newly infected with HIV during the study period, and it was estimated

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Reason for exclusion from GRADE analyses: commentary or not an acceptable study design that for every 1% increase in ART use in a province the odds ratio for reducing new HIV diagnoses was 1.08.

Conclusions: The province with the highest ART coverage showed a steady decline in the rate of new HIV infections and provides evidence of the need to expand ART coverage in Canada.

6 R. Kamwi, N. Hamunime, M. Odiit, J.

Gweshe, A. Muadinohamba, E. Shihepo, H. Van Renterghem, A. Jonas, M. De Klerk, M. Mahy, N. Forster, K. Kahuure.

Treatment as prevention in a country with high ART coverage: the Namibia example.

Abstract presentation at AIDS 2012.

Population and setting: New HIV infections and current HIV-positive people in Namibia using data from 2000 to 2011.

Results: New HIV infections decreased from 23 000 in 2000/2001 to 9000 in 2010/2011, a decrease of 61%. The number of people receiving ART as of March 2012 was 107 000, representing 88% of the eligible people according to current WHO treatment guidelines (<350 cells/mm³); if this threshold was increased to >500 cells/mm³, the number of people eligible would increase by an estimated 20%. If the guidelines were changed to initiate ART when the CD4 count falls below 500 cells/mm³ (coverage of at least 95%), the investigators calculate that there would be 4890 deaths averted, 14 000 infections averted and 25 000 life-years gained by 2025. If the treatment guidelines were to change from <350 cells/mm³ to

<500 cells/mm³ (coverage of at least 95%) and coverage of 50% of those with CD4 count >500 cells/mm³, 6820 deaths would be averted, 27 000 infections would be averted and 37 000 life-years would be gained by 2025.

Conclusions: Namibia should further expand ART not only to reduce morbidity and mortality and to realize the target of a 50% reduction in sexual transmission by 2015 but also substantially reduce the number of people newly infected requiring ART in the long term.

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Reason for exclusion from GRADE analyses: commentary or not an acceptable study design 7 Katz MH, Schwarcz SK, Kellogg TA,

Klausner JD, Dilley JW, Gibson S, McFarland W. Impact of highly active antiretroviral treatment on HIV

seroincidence among men who have sex with men: San Francisco. Am J Public Health 2002;92(3):388-94.

Population and setting: men who have sex with men living with HIV in San Francisco analysed from 1995 to 1999.

Results: The use of HAART among men who have sex with men living with HIV increased from 4% in 1995 to 54% in 1999, and the annual HIV incidence increased from 2.1% in 1994 to 4.2% in 1999.

Conclusions: The use of HAART increased among men who have sex with men with AIDS, as did also the proportion of men who have sex with men reported unsafe sexual practices. Additionally, the annual HIV incidence rate increased, suggesting that any benefit from HAART on risk per sexual contact was offset by general sexual risk increases.

8 Law MG, Woolley I, Templeton DJ, Roth N, Chuah J, Mulhall B, Canavan P, McManus H, Cooper DA, Petoumenos K;

Australian HIV Observational Database (AHOD). Trends in detectable viral load by calendar year in the Australian HIV

observational database. J Int AIDS Soc 2011;14:10.

Study design: Observational study database.

Population and setting: 2439 HIV-positive people in Australia from 1997 to 2009.

Intervention: No intervention (observational study).

Comparator: No comparator (observational study).

Results: Observed detectable viral load in patients receiving ART declined to 5.3% in the first half of 2009, while predicted detectable viral load based on multivariate models, allowing for patient loss to follow up, also declined over time, but at higher levels, to 13.8% in 2009.

Conclusions: Predicted detectable viral load in Australian HIV Observational Database patients receiving ART declined over calendar time, albeit at higher levels than observed.

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Reason for exclusion from GRADE analyses: commentary or not an acceptable study design 9 K. Manavi, K. Martin, E. Smit, J. Hawker.

Community viral load counts and new HIV infected patients in Birmingham, UK between 2006 and 2011. Abstract presentation at AIDS 2012.

Population and setting: HIV-positive people in Burmingham, UK from 2006 to 2010.

Results: New HIV infections increased slightly from 149 in 2006 to 153 in 2010. Among those with HIV, the mean CVL decreased from 17,000 copies/ml in 2006 to 9905 copies/ml in 2010, and the proportion with VL <50 copies/ml increased from 58% in 2006 to 72% in 2010.

Conclusions: Reduction in CVL in Birmingham between 2006 and 2011 was not associated with reduced number of people newly infected with HIV.

This may be a sign of the city’s inadequate HIV testing efforts.

10 Montaner JS, Lima VD, Barrios R, Yip B, Wood E, Kerr T, Shannon K, Harrigan PR, Hogg RS, Daly P, Kendall P. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet 2010;376(9740):532-9.

Study design: Ecological analysis using registries data.

Population and setting: Data from HIV-positive individuals living in British Colombia, Canada collected between 1996 and 2009.

Results: For every 100 additional individuals receiving ART, the number of new HIV cases

decreased by a factor of 0.97 (not considering immune status) and, for every 1 log10 decrease in viral load, the number of new HIV cases decreased by a factor of 0.86. ART initiation at specific immune status levels was assessed through the median CD4 cell count at baseline for the entire population. The median CD4 cell count pre-ART initiation ranged from a high of 310 cells/mm³ in 1997 to a low of 150 cells/mm³ in 2003.

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Reason for exclusion from GRADE analyses: commentary or not an acceptable study design Conclusions: The authors concluded that their results support the proposed secondary benefit of HAART used within existing medical guidelines to reduce HIV transmission.

11 Montaner J et al. Expanded HAART coverage is associated with decreased HIV/AIDS morbidity and HIV new diagnoses: an update on the “treatment as prevention” experience in British

Columbia, Canada. Abstract presentation at AIDS 2012.

Population and setting: Update of Montaner 2012 using data from individuals with HIV living in British Columbia, Canada collected between 1996 and 2011.

Results: The number of individuals on HAART has increased significantly over the study period, while median baseline CD4 cell count has increased

significantly and plasma VL has steadily decreased in recent years (6% of people had VL <50 copies/ml in 1996 compared to 56% in 2011). The all-cause death rate among people with HIV in British Columbia declined over the study period (P = 0.19). Finally, the number of people newly diagnosed with HIV has continued to decrease significantly (P = 0.0005) to its current nadir of 301 cases in 2010.

Conclusions: The authors concluded that, in this programme, ART expansion has been strongly and significantly associated with decreases in HIV new diagnoses, as well as AIDS diagnoses and death reports.

12 Porco TC, Martin JN, Page-Shafer KA, Cheng A, Charlebois E, Grant RM, Osmond DH. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS

2004;18(1):81-8.

Study design: Observational study database.

Population and setting: 534 men who have sex with men in San Francisco followed from 1994 to 1999.

Intervention: No intervention (observational study).

Comparator: No comparator (observational study).

Results: Using mathematical modelling, the authors found that conservatively assuming a constant prevalence of HIV infection between 1994 and 1999, HIV infectivity decreased from 0.120 prior to widespread use of HAART to 0.048 after the

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Reason for exclusion from GRADE analyses: commentary or not an acceptable study design widespread use of HAART – a decline of 60%

(P = 0.03).

Conclusions: The authors conclude that the use of HAART by people with HIV in a community appears to reduce their infectiousness and therefore may provide an important HIV prevention tool.

13 Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, Harrigan PR, Montaner JS. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ 2009;338:b1649.

Study design: Prospective cohort study

Population and setting: 622 HIV-positive and 1429 HIV-negative people who inject drugs from

Vancouver, Canada followed from 1996 to 2007.

Intervention: No intervention (cohort study).

Comparator: No comparator (cohort study).

Results: Among 1429 people who inject drugs without HIV, there were 155 HIV seroconversions, resulting in an incidence density of 2.49 (95%

confidence interval 2.09 to 2.88) per 100 person-years.

Among HIV-uninfected people who inject drugs, Cox models adjusting for high-risk sexual activities suggested that community viral load was independently related to the time to HIV

seroconversion (hazard ratio=3.32 per log10 increase).

Conclusions: As community viral load increases, so does the risk for new HIV infection among people who inject drugs.