Occupational exposure to HIV: experience at a tertiary care center. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. Drug-induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis. Effects of a peer-led behavioral intervention to reduce HIV transmission and promote serostatus disclosure among HIV-seropositive gay and bisexual men. Behavioral drug and HIV risk reduction counseling (BDRC) with abstinence-contingent take-home buprenorphine: a pilot randomized clinical trial. Multidisciplinary HIV adherence intervention: a randomized study. Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal. Impact of telephonic psycho-social support on adherence to post-exposure prophylaxis (PEP) after rape. Telephone support to improve antiretroviral medication adherence: a multisite, randomized controlled trial.
We examined our hospital-based occupational health clinic's experience with combination antiretroviral therapy for postexposure prophylaxis for human immunodeficiency virus (HIV). Over a 12-month period, 68 workers started postexposure prophylaxis: 23 with zidovudine and lamivudine and 45 with zidovudine, lamivudine, and indinavir. Fifty-one (75%) of the 68 workers starting postexposure prophylaxis reported one or more side effects. Side effects were more common among those taking three drugs. Many workers failed to complete the recommended 28-day regimen because of the side effects of the various treatments. The estimated mean cost for evaluations, prophylaxis, and monitoring of exposed workers was $669 per reported exposure. In our experience, major challenges in carrying out the current HIV postexposure prophylaxis guidelines include expeditious source testing, improved staff education and prevention measures, and scrupulous monitoring of workers taking combination antiretroviral drugs for postexposure prophylaxis, with consideration of alternate regimens for intolerant workers. The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood.
                We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert.
                Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52).
                The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective. In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3-4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered. To evaluate the effects of an enhanced peer-led intervention on transmission risk behavior and serostatus disclosure of HIV-seropositive gay and bisexual men.
                A randomized intervention trial.
                HIV-seropositive gay and bisexual men were recruited from New York City and San Francisco and were randomly assigned to either a standard or an enhanced intervention. The standard intervention consisted of one session that provided safer sex information. The enhanced intervention consisted of six sessions and included safer sex information, interactive learning activities, and discussion groups that were facilitated by HIV-seropositive peers. Participants completed audio computer-assisted self interview (A-CASI) assessments at baseline and 3 and 6-month follow-ups. Optional testing for sexually transmitted infections was offered at baseline and the 6-month follow-up.
                A total of 811 participants met the inclusion criteria for outcome analyses. Of these, 85 and 90% were retained for the 3 and 6-month follow-ups, respectively. Compared with the standard intervention, fewer men assigned to the enhanced intervention reported unprotected receptive anal intercourse with a negative or unknown-serostatus partner at 3 months (21 versus 26%, P < 0.05). However, there were no other significant differences in transmission risk or serostatus disclosure at 3 or 6 months.
                The enhanced intervention was associated with only a limited reduction in transmission risk at 3 months relative to the standard intervention. The characteristics of the intervention that may have reduced its efficacy are identified and directions for future research are suggested. This pilot randomized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment (BMT), provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine. After a 2-week buprenorphine and stabilization period, heroin dependent individuals (n=24) in Muar, Malaysia were randomly assigned to Standard Services BMT (physician administered advice and support, and weekly, non-contingent medication pick-up) or Enhanced Services (nurse-delivered manual-guided behavioral drug and HIV risk reduction counseling (BDRC) and abstinence-contingent take-home buprenorphine (ACB), 7 day supply maximum). Outcomes included retention, proportion of opioid-negative urine tests, self-reported drug use, and self-reported HIV risk behaviors. 12/12 (100%) of Enhanced Services and 11/12 (92%) of Standard Services participants completed the entire protocol. The proportion of opioid-negative urine tests increased significantly over time for both groups (p<0.001), and the reductions were significantly greater in the Enhanced Services group (p<0.05); Enhanced Services group achieved higher overall proportions of opiate negative urine toxicology tests (87% vs. 69%, p=0.04) and longer periods of consecutive abstinence from opiates (10.3 weeks vs. 7.8 weeks, p=0.154). Both groups significantly reduced HIV risk behaviors during treatment (p<0.05), but the difference between Enhanced and Standard Services (26% vs. 17% reductions from the baseline levels, respectively) was not statistically significant (p=0.9). Manual-guided behavioral drug and HIV risk reduction counseling and abstinence-contingent take-home buprenorphine appear promising for adding to the efficacy of office-based BMT provided with limited drug counseling and medication oversight. Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001). To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults.
                Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal.
                Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis.
                Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2).
                Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal. South Africa has one of the highest rates of both rape and HIV infections. Of great concern is the possibility of HIV transmission during the assault, but adherence to post-exposure prophylaxis (PEP) has been varied and low. We developed a telephonic psycho-social support, leaflet and adherence diary intervention for rape victims and tested its impact on adherence to PEP. A randomised control trial was conducted in the Western and Eastern Cape and 279 rape survivors were enrolled in two arms. The intervention involved the providing of an information leaflet including an adherence diary and follow-up support through telephone calls by a counsellor during the 28 days of taking the PEP. The controls received the leaflet. Follow-up interviews and tablet checks were done with 253 participants to assess adherence. The primary outcome was completion of 28 days of PEP with no more than three missed doses (94% adherence). There was more adherence in the intervention arm (38.2% vs. 31.9%), but the estimated intervention effect of 6.5% (95% CI: -4.6 to 17.6%) was not statistically significant, p=0.13. The intervention was associated with the reading of the pamphlet (p=0.07) and an increased use of the diary (p=0.01), but did not reduce depressive psychopathology. Overall adherence was greater amongst those who read the leaflet and used the medication diary. The study showed that the intervention was not effective in significantly improving adherence and adherence levels were low in both study arms. Further research to understand reasons for non-adherence is needed before further interventions are developed. To determine whether proactive telephone support improves adherence to antiretroviral therapy (ART) and clinical outcomes when compared to standard care.
                A multisite, randomized controlled trial (RCT) was conducted with 109 ART-naive subjects coenrolled in AIDS Clinical Trials Group (ACTG) 384. Subjects received standard clinic-based patient education (SC) or SC plus structured proactive telephone calls. The customized calls were conducted from a central site over 16 weeks by trained registered nurses. Outcome measures (collected over 64 weeks) included an ACTG adherence questionnaire and 384 study endpoints.
                For the primary endpoint, self-reported adherence, a significantly better overall treatment effect was observed in the telephone group (P = 0.023). In a post hoc analysis, composite adherence scores, taken as the first 2 factor scores from a principal components analysis, also found significant intervention benefit (P = 0.023 and 0.019 respectively). For the 384 primary study endpoint, time to regimen failure, the Kaplan-Meier survival curve for the telephone group remained above the SC group at weeks 20 to 64; a Cox proportional hazard model that controlled for baseline RNA stratification, CD4, gender, age, race/ethnicity, and randomized ART treatment arm suggested the telephone group tended to have a lower risk for failure (hazard ratio = 0.68; 95% confidence interval: 0.38 to 1.23).
                Findings indicate that customized, proactive telephone calls have good potential to improve long-term adherence behavior and clinical outcomes.
The use of occupational PEP is based on limited direct evidence of effect. However, it is highly unlikely that a definitive placebo-controlled trial will ever be conducted, and, therefore, on the basis of results from a single case-control study, a four-week regimen of PEP should be initiated as soon as possible after exposure, depending on the risk of seroconversion. There is no direct evidence to support the use of multi-drug antiretroviral regimens following occupational exposure to HIV. However, due to the success of combination therapies in treating HIV-infected individuals, a combination of antiretroviral drugs should be used for PEP. Healthcare workers should be counseled about expected adverse events and the strategies for managing these. They should also be advised that PEP is not 100% effective in preventing HIV seroconversion. A randomized controlled clinical trial is neither ethical nor practical. Due to the low risk of HIV seroconversion, a very large sample size would be required to have enough power to show an effect. More rigorous evaluation of adverse events, especially in the developing world, are required. Seeing that current practice is partly based on results from individual primary animal studies, we recommend a formal systematic review of all relevant animal studies.