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Risk of HIV-1 transmission for parenteral exposure and blood transfusion: a systematic review and meta-analysis

Baggaley, Rebecca Fa; Boily, Marie-Claudea,b; White, Richard Gb; Alary, Michelc,d

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doi: 10.1097/01.aids.0000218543.46963.6d
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There has been considerable debate concerning the relative contribution of different modes of transmission to the HIV-1 epidemic in Africa [1–6]. The main mode of transmission, especially in resource-poor settings, is considered to be unprotected heterosexual sex. However, one group of researchers believe that the role of iatrogenic transmission, particularly unsafe medical injections, has been vastly underestimated [1,7]. Accurate estimates of transmission probabilities for contaminated injections are currently lacking, but are needed to assess the risk of infection through this route, and its contribution to the HIV/AIDS pandemic, within resource-poor settings in particular [8,9]. More data are available for single, accidental percutaneous injuries with needles or other sharp objects contaminated with infectious material from HIV patients, usually among health care workers and laboratory workers. This information can help in estimating the risk per contaminated medical injection. A limited number of studies have estimated the risk of HIV transmission per injection drug user (IDU) injection; this information can also help estimate the risk from medical injections, as well as the risk from IDU. The other main iatrogenic risk is unsafe blood transfusions. Therefore in this paper we present the results of a systematic review and meta-analysis on HIV-1 infectivity per single exposure for parenteral modes of transmission (per contaminated medical injection, IDU injection and accidental percutaneous exposure) and blood product transfusion. The results can be used to assess the relative contributions of these modes of transmission.


The systematic review was undertaken according to the QUORUM checklist [10], revised for review of non-randomized control trial studies.


For parenteral modes of transmission, a search was performed using the criteria for publication titles to contain: HIV AND (infectivity OR infectiousness OR transmission OR probability) AND (parenteral OR occupational OR percutaneous OR needle OR drug use OR intravenous OR health care). Databases used were PubMed MEDLINE at PubMed (National Library of Medicine (NLM), EMBASE ( and Science Direct Parenteral exposure is defined as subcutaneous, intramuscular or intravenous contact with blood or other body fluid of an HIV-1 infected individual, but not mucocutaneous contact. Percutaneous injuries involving splashes of infected fluid onto open wounds were excluded. For blood transmission, the parenterally-related terms were exchanged for: iatrogenic OR blood OR transfusion OR haemophilia OR hemophilia.

Titles (and abstracts, where available) were scanned for relevance, identifying papers requiring further consideration. Bibliographies of all relevant articles were checked for additional relevant publications. There was no restriction by study design or language of publication.


Exclusion criteria were all abstracts-only pre-1995 and infectivity estimates based on sample sizes of less than 10. Where the most recent report of a prospective study was an abstract, further study information was also taken from the most recent preceding publication, with both abstract and publication cited in the tables. A report by the Public Health Laboratory Service [11,12] was useful to decipher truly independent results and to obtain details on studies for which primary sources were unavailable.

Quantitative data synthesis

To improve comparability of studies, all confidence intervals were recalculated using the Wilson ‘score’ method without continuity correction [13] as recommended by Newcombe [14], (except for Hudgens et al. [15,16]). Forest plots were constructed using MS Excel (Microsoft Corp., Redmond, Washington, US).


For accidental percutaneous and blood product exposures, summary estimates and associated 95% confidence intervals (95% CI; based on a fixed effects model) are presented on the forest plots. Two different weighting schemes [sample size (sz) or precision (p)] were used for comparison. Summary estimates used sample sizes for weights (referred to as pooled estimates, psz) or used the inverse variance method [17] with the precision, defined by the wider bound of the asymmetric Wilson ‘score’ confidence interval [upper bound for needlestick (SiUB) and lower bound for blood (SiLB) exposure], divided by z, used for weights rather than the standard error. This is because needlestick transmission risk is small and blood transmission risk is large, so many studies with 0% (100%) seroconversion for needlestick (blood transfusion) exposure give a standard error of zero and infinite weights.

for needlestick transmission, and

for blood transmission; where ni is the sample size for study, and z = 1.96 denotes the standard normal deviate associated with a two-tailed probability α = 5%.

We tested heterogeneity between studies using the heterogeneity statistic [17].


Summary of the search

Sixty estimates for parenteral (medical, IDU and accidental injections) and 14 for blood product exposure were found. After evaluation, 30 articles were included for parenteral exposure [15,16,18–45], providing 26 estimates, and 10 articles were included for blood product exposure [46–55], providing 11 estimates. The 30 included studies providing estimates of parenteral transmission consisted of three papers describing IDU risk [15,16,18], 26 papers providing 21 estimates for accidental percutaneous injury [20–45] (where five publications were accompanied by a more recent abstract from which the estimate was taken [27,28,34,35,37–41,56]), and one reporting both percutaneous injury and contaminated injection risks [19]. The 11 estimates for blood product exposure included two from Ward et al. [49], but only the estimate in which blood products were proved to be contaminated was included in summary estimates. Forest plots of infectivity estimates are presented in Figs 1 and 2. Summaries of the characteristics of included and excluded studies are available on request.

Fig. 1
Fig. 1:
Summary of studies estimating transmission probability for parenteral exposure to HIV. Bars represent 95% confidence intervals (CI) except for Gisselquist [19], which is a range. psz: estimate weighted by sample size; pp: estimate weighted by precision (adapted inverse variance method) – see details in method. *For needlestick and other accidental sharp injury only, without excluded studies and Gisselquist 2002 estimate [19] (no sample size available). **All excluded studies except for superseded publications and those without sample sizes.
Fig. 2
Fig. 2:
Summary of studies estimating transmission probability per contaminated blood product transfusion. Bars represent 95% confidence intervals (CI). psz: estimate weighted by sample size; pp: estimate weighted by precision (adapted inverse variance method) – see details in method. *All excluded studies except for superseded publications and those without sufficient data.

Parenteral exposure

Nineteen of the 25 estimates were derived from prospective studies (one for IDU and 18 for needlestick injury), in which study participants were typically followed up for about 9 to 12 months following one contact/exposure for needlestick or many injection events for IDUs. Studies tended to be prospective in that health care workers or laboratory workers were encouraged to report exposures, after which they were followed up, rather than enrolment in a study before exposure. Two studies of needlestick transmission were retrospective with health care workers sometimes reporting more than one contact/exposure [20,21]. One was of unspecified design [44], while Gisselquist [19] used data from a case–control study [57] to derive an estimate. The remaining two estimates, one for IDU [18] and one for contaminated injections [19], were also indirectly derived from mathematical models (one for each type of exposure).

Injection drug users

Infectivity estimates for IDU ranged from 0.63% [16] to 2.4% [18] (median = 0.8%) [15,16,18] (Fig. 1). Kaplan and Heimer favoured their lower estimate of 0.67% per exposure [18], and Hudgens et al. [15] concluded that their 0.84% estimate was consistent with this. Given the heterogeneity of estimates between studies and subtypes, it was inappropriate to combine results.

Contaminated injections

The only study available evaluated the estimated infectivity per contaminated injection as 1.9–6.9%, a very wide range, based on data of limited quality from nosocomial outbreaks in Russia, Romania and Libya [19] and on a large number of assumptions.

Accidental percutaneous injury

Infectivity estimates for accidental percutaneous injury are more reliable than those for IDU and contaminated injections, primarily because the number of exposures is usually one per person, and the infection status of the index case can be determined relatively easily. In the few instances where an individual experienced more than one exposure, these were counted as separate events in our analysis. All studies calculated transmission probabilities as the proportion of exposure events resulting in transmission, except for Gisselquist [19], who calculated the HIV transmission probability for deep injuries only, to be used as an approximation for contaminated medical injections. The author makes a large number of assumptions, and deep injuries may involve transfer of more infective fluid than contaminated injections. As no confidence intervals were provided or could be derived, this estimate was excluded from summary estimates.

Infectivity estimates for needlestick exposure from all 22 studies ranged from 0.00% [21–30,32–35,42] to 2.38% [20] (pp = 0.23%; 95% CI = 0.00–0.46%; psz = 0.24%; 95% CI = 0.14–0.40%, n = 21). Transmission of HIV via this route is uncommon and therefore the majority of studies produced estimates of 0.00% ([21–30,32–35,42], n = 13); the average sample size for these studies was 67 injuries, compared with 644 injuries for studies providing non-zero estimates. When including only studies reporting at least one transmission event and excluding Gisselquist [19], estimates ranged from 0.18% [36,37] to 2.38% [20] (pp = 0.25%; 95% CI = 0.01–0.49%). Estimates of included studies with pp and psz gave similar results, but we prefer to report pp which produced wider confidence intervals (Table 1). There was no evidence of heterogeneity between studies (df = 20; P = 1).

Table 1
Table 1:
Summary transmission probabilities for contaminated accidental needlestick or sharp injuries and blood product transfusion, under various inclusion criteria and for pooled data and weighted average methods.

Analysis of subsets of studies is shown in Table 1. The estimate based on studies with no other reported risk factors for HIV transmission (pp = 0.13%; 95% CI = 0.00–0.54%) was not significantly different from the overall estimate (pp = 0.23%). The infectivity of symptomatic patients (AIDS or AIDS plus AIDS-related complex patients) approximately doubles (psz) or triples (pp) the risk. However, results should be interpreted with caution because of the small sample sizes.

Blood product transfusion

Infectivity estimates for transmission per transfusion with infected blood products are presented in Fig. 2. Eight of the 10 estimates are based on retrospective and two on longitudinal studies following transfusion with infected blood products [52,55]. Infectivity estimates ranged from 27.0 to 100.0%, with summary estimates of pp = 82.2% (95% CI = 79.0–85.4%) and psz = 80.2% (95% CI = 76.7–83.3%). However, the 10 studies displayed considerable heterogeneity (Q = 198.36; χ92: P < 0.0001). The six studies which could confirm that donations were contaminated [49,50,52–55] were more homogeneous (Q = 5.99; χ62: P = 0.42431) and produced higher infectivity estimates (range, 88.3–100.0%; pp = 92.5%; 95% CI = 89.0–96.1%).


Transmission probabilities are difficult to measure for most modes of transmission, partly because of difficulty in confirming the infected source, and also because they depend on other risk factors, such as HIV viral load [58] and exposure to antiretroviral therapy [59]. The lack of data for both IDU and contaminated medical injection exposure means that transmission probabilities can only be indirectly derived from studies on HIV transmission per accidental percutaneous injury. The risk of infection from percutaneous accidents depends on factors that influence exposure to a greater volume of blood (e.g. visible blood on the device, procedures involving needle placement directly into a vein or artery, etc), viral load (e.g. clinical status of the source patient, post-exposure prophylaxis), which affect the ‘effective’ viral dose received [57,60]. The type of injection equipment affects infectivity because syringes with detachable needles retain – and probably transfer – substantially more blood than integral cannula syringes with a permanently attached needle [61–63]. Laboratory studies have suggested that a greater volume of blood is transferred by deeper injuries and by hollow-bore needles (especially those with larger gauges) [64].

The reliability of data from studies estimating infectivity per single contaminated medical injection or IDU injection is affected by more factors than studies on accidental percutaneous exposure. The estimates produced by Kaplan and Heimer [18] and Hudgens et al. [15,16] are compatible with each other and are based on good quality data, considering the difficulty in obtaining information in this area, with thorough analyses. Since HIV-1 CREØ1AE (formerly subtype E) is predominantly contained in South-east Asia and is potentially more infectious than other types, the adjusted estimate for subtype B, 0.63% (95% CI, 0.41–0.92%) is used as the average risk per IDU injection, which is in close accord with Kaplan and Heimer's estimate of 0.67%. Gisselquist's estimate of transmission risk per contaminated injection [19] is not compatible with these estimates and the methodology has been criticized [65]. The risk from contaminated injections is likely to be less than for IDU because IDU injections are intravenous, whereas medical injections in sub-Saharan Africa are usually intramuscular, blood contamination of needles after use for intramuscular injection is infrequent [65], and washing of needles substantially reduces risk [66].

While deliberate injections may involve more transfer of fluid from the device than for accidental punctures, the fluid may contain less infectious material because health care workers will often have cleaned needles between patients. The combined result of these competing effects is unknown and subjective. The true infectivity of contaminated injections is unlikely to be less risky than accidental injuries or to be more risky than for IDU injections. To reflect this uncertainty we propose a transmission probability estimate for contaminated injections ranging between our estimates for these modes: 0.24–0.65%, with a point estimate being the midpoint of 0.45% risk per exposure. Unlike sexual transmission probabilities, these estimates are unlikely to vary substantially by geographical location. Recent estimates of per contact HIV infectivity for sexual transmission in Africa are comparable to this [67,68]. The frequency of sexual exposure is far higher than the frequency of unsafe injections, and so heterosexual sex is the main mode of transmission, with unsafe injections playing a minor role.

Infectivity estimates for infected blood transfusions are much higher than for other modes of HIV-1 transmission due to the far larger viral dose per exposure than for other routes. Relatively few studies aiming to quantify the infectivity of HIV-1 via blood transfusion were found, perhaps because it was clear from the start that this risk was likely to be extremely high, and because this source of infection was identified and eliminated fairly early in the epidemic, at least in industrialised countries. However, the frequency of unsafe blood transfusions compared to sexual contacts is extremely small.


Infectivity estimates per IDU injection range from 0.63% [16] to 2.4% [18], median = 0.8%. The only estimate for medical injections was 1.9–6.9% [19]. The estimate per accidental percutaneous injury is pp = 0.23% (95% CI = 0.00–0.46%). We propose a transmission probability estimate per contaminated injection of 0.45% (range, 0.24–0.65%). The transmission probability per contaminated blood product exposure is pp = 92.5% (95% CI 89.0–96.1%). In view of this and the frequency of unsafe injections and blood transfusion compared to unprotected sexual contacts, the role of iatrogenic transmission in resource-poor settings has not been underestimated.

It is important to provide reliable estimates of transmission probabilities for iatrogenic modes of transmission, in order to predict their relative impact on the HIV/AIDS pandemic. Our estimates are based on the most comprehensive review of the literature and best studies, and will be critical when assessing the contribution of these routes of infection to HIV incidence and designing appropriate prevention strategies.


Sponsorship: R.F.B. is grateful to GlaxoSmithKline for financial support. M.A. is a National Researcher of the Fonds de la recherche en santé du Québec (grant no. 8722).

Potential conflict of interest: R.F.B. was supported by an unrestricted educational grant from GlaxoSmithKline.


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                                transmission probability; infectivity; infectiousness; injections; intravenous; needlestick; blood transfusion

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