Only one of three cohort studies fully reported on the proportion of participants with detectable HIV in both the STD group (pre- and posttreatment) and the non-STD group (providing two measures a similar time apart). Similarly, only one study reported fully on HIV load in both groups. Ghys et al14 showed a modest reduction in the proportion of women with detectable HIV after successful STD treatment (39% to 29%; P = 0.05), whereas levels remained stable over time in the non-STD group (Table 3). The proportion with detectable HIV post-STD treatment (29%) remained higher than the proportion in the non-STD group (15-17%). Cohen et al11 reported a substantial reduction in HIV load following successful STD treatment in men, from 12.4 to 4.12 × 104 copies/ml at 2 weeks (P = 0.0001), whereas HIV load remained relatively stable in those without an STD (1.51−2.5 × 104 copies/ml; P = 0.42). Posttreatment viralload levels did not reach levels of the non-STD group.
This systematic review and data synthesis of observational studies reporting on the association between coinfection with a STD and HIV shedding in genital-tract secretions, and on the effect of STD treatment, failed to find many studies of high quality. This reflects the difficulty conducting this type of research.
Our pooled data suggest a modest association between HIV shedding and STD. The association is stronger for infection with N gonorrhoeae than for infection with C trachomatis. We note that the proportion of patients with detectable HIV is increased only modestly (from 32% to 41%) by coinfection with N gonorrhoeae. Similarly, data were only available from one study of appropriate design11 to suggest that HIV load is substantially increased in the genital secretions of men with urethritis. This study11 also suggests that viral load is higher among men with N gonorrhoeae infection (who have greater urethral inflammation11) than among those with C trachomatis infection. These observations are important because the infectivity of HIV through sexual transmission is directly related to HIV viral load in genital secretions, which is similar to that in parenteral and mother-to-child transmission.55
Furthermore, we found only limited data from studies of appropriate design to suggest that the proportion of patients with detectable genital HIV shedding falls after successful STD treatment.14 Despite a large sample size, the modest reduction from 39% to 29% was of borderline statistical significance. Also, the proportion of persons with detectable HIV after treatment (29%) remained almost double that of persons without an STD with detectable HIV (Table 3).
The evidence that HIV load in genital secretions is substantially reduced after successful STD treatment is stronger; however, only one study of adequate design reported on this.11 It should be noted that even 2 weeks posttreatment, viral load remained higher in the STD group than in the control group (Table 3). The few studies of appropriate design that we identified limit the confidence of these conclusions. It is worth noting that all studies are from Africa, and most are from Kenya. As such, there may be some concern about the generalizability of the results; further studies in different settings are warranted. We pooled data from men and women because we aimed to increase the power of our analysis and because we observed little heterogeneity in the data (Figures 1 and 2). As more data becomes available, metaanalyses of male and female data separately would be valuable.
The value of systematic review and metaanalysis of randomized controlled trials is now well recognized.56 The application of systematic review to observational studies is also recognized as valid; however, metaanalysis has a less prominent role because there is a real danger of producing precise, but spurious, results.58 We conducted a rigorous search for relevant studies, critically appraised study quality against predefined criteria,56 and only pooled data from studies that demonstrated little heterogeneity and that reported data consistently (e.g., by organism). As new data becomes available, this review can be updated.
Systematic review is also useful because it highlights important deficiencies in study design and reporting, which can be rectified in the future. We did not include several studies because of the lack of adequate control-group measures. This is important because HIV shedding in genital-tract secretions is frequently variable over time,14,22,23,30 and if any change is to be attributed to STD treatment, it is important to have a control group without an STD for which repeat measures are made.
It is worth noting that the included studies only reported the effect of STD treatment among patients who were successfully treated. Thus, we are unsure of what the effect of STD treatment on HIV is in an unselected group of STD patients treated with syndromic management in a developing country, for example. It may be that the absolute effect on overall HIV transmission is relatively small. This may be especially so if asymptomatic patients are targeted,8 but is less likely if symptomatic STD patients (who probably have a higher viral load due to greater inflammation) are targeted.7
Relatively poor follow-up procedures may be a feature of studies among sex workers and patients with STDs; however, Ghys et al14 reported a 70% follow-up rate, and Cohen et al11 reported an 86% rate. There was marked variation in the study population used in the included studies, ranging from sex workers to pregnant women, with correspondingly variable baseline levels of STD and HIV. Of more concern is the different HIV-detection methods used. DNA and RNA assays measure different factors, and we are careful not to overinterpret pooled data from studies that use different assays. It will be important for researchers to agree on a common standard assay. Diagnosis of chlamydial infection may be particularly difficult, and a wide range of diagnostic methods are used, making interpretation of results difficult. It was also difficult to interpret some data because not all studies reported results by infecting organism. It may be preferable to report by individual organism, by STD syndrome, and by number of patients with any STD, because this might allow some perspective to be gained on the impact of STD-treatment policies on HIV transmission.
For the future, a series of cohort studies including men and women who are recruited from a variety of settings, with high levels of follow up, and with repeat standardized measures performed in each group, and with adjustment for other risk factors for shedding would provide useful information regarding the relationship between STD and HIV and between STD treatment and HIV in genital secretions. Further, it will be useful to try to explore the relative importance of asymptomatic and symptomatic STD on HIV genital-tract shedding.
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