Joshua D. Bamberger

Adherence to protease inhibitors, Hiv-1 viral load, and development of drug resistance in an indigent population

ObjectiveTo examine the relationship between adherence, viral suppression and antiretroviral resistance in HIV-infected homeless and marginally housed people on protease inhibitor (PI) therapy. Design and settingA cross-sectional analysis of subjects in an observational prospective cohort systematically sampled from free meal lines, homeless shelters and low-income, single-room occupancy (SRO) hotels. ParticipantsThirty-four HIV-infected people with a median of 12 months of PI therapy. Main outcomesAdherence measured by periodic unannounced pill counts, electronic medication monitoring, and self-report; HIV RNA viral load; and HIV-1 genotypic changes associated with drug resistance. ResultsMedian adherence was 89, 73, and 67% by self-report, pill count, and electronic medication monitor, respectively. Thirty-eight per cent of the population had over 90% adherence by pill count. Depending on the measure, adherence explained 36–65% of the variation in concurrent HIV RNA levels. The three adherence measures were closely related. Of 20 genotyped patients who received a new reverse transcriptase inhibitor (RTI) when starting a PI, three had primary protease gene substitutions. Of 12 genotyped patients who received a PI without a new RTI, six had primary protease gene substitutions (P < 0.03). ConclusionA substantial proportion of homeless and marginally housed individuals had good adherence to PI therapy. A strong relationship was found between independent methods of measuring adherence and concurrent viral suppression. PI resistance was more closely related to the failure to change RTI when starting a PI than to the level of adherence.

Naloxone Distribution and Cardiopulmonary Resuscitation Training for Injection Drug Users to Prevent Heroin Overdose Death: A Pilot Intervention Study

Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin overdose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants’ knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.

Feasibility of Postexposure Prophylaxis (PEP) against Human Immunodeficiency Virus Infection after Sexual or Injection Drug Use Exposure: The San Francisco PEP Study

The feasibility of providing postexposure prophylaxis (PEP) after sexual or injection drug use exposures to human immunodeficiency virus (HIV) was evaluated. PEP was provided within 72 h to individuals with exposures from partners known to have or to be at risk for HIV infection. PEP consisted of 4 weeks of antiretroviral medications and individually tailored risk-reduction and medication-adherence counseling. Among 401 participants seeking PEP, sexual exposures were most common (94%; n=375). Among sexual exposures, receptive (40%) and insertive (27%) anal intercourse were the most common sexual acts. The median time from exposure to treatment was 33 h. Ninety-seven percent of participants were treated exclusively with dual reverse-transcriptase inhibitors, and 78% completed the 4-week treatment. Six months after the exposure, no participant developed HIV antibodies, although a second PEP course for a subsequent exposure was provided to 12%. PEP, after nonoccupational HIV exposure, is feasible for persons at risk for HIV infection.

Use of postexposure prophylaxis against HIV infection following sexual exposure does not lead to increases in high-risk behavior

Background: The effectiveness of postexposure prophylaxis (PEP) following occupational exposure to HIV has prompted advocacy for PEP following sexual or drug-use exposures. Objective: To evaluate the concern that the availability of PEP for sexual or drug-use exposures might result in behavioral disinhibition. Design: Non-randomized trial of 397 adults with high-risk sexual or drug-use exposures within the prior 72 h. Interventions: Antiretroviral medication for 4 weeks and five counseling sessions. Main outcome measurements: Participants were followed for 12 months for repeat request for PEP and for changes compared with pre-enrollment in overall high-risk behavior and the acquisition of sexually transmitted diseases (STD) and HIV. Results: After 12 months following receipt of PEP, the majority of participants (83%) did not request a repeat course of PEP. At 12 months after exposure, 73% of participants reported a decrease compared with baseline in the number of times they had performed high-risk sexual acts; 13% reported no change, and 14% had an increase. Most participants (85%) had no change in the incidence of STD; 8.5% had a decrease and 6.8% an increase. Three homosexual men seroconverted for HIV (none associated with the presenting exposure) for a rate of 1.2/100 person-year, equivalent to rates in San Francisco among all homosexual men. Conclusions: After receipt of PEP consisting of antiretroviral medication and behavioral counseling following a potential sexual exposure to HIV, most individuals do not increase high-risk behavior. Coupled with prior safety and feasibility data, this lack of behavioral disinhibition suggests that use of PEP should be routinely considered following high-risk sexual exposures.

Overdose Prevention and Naloxone Prescription for Opioid Users in San Francisco

Opiate overdose is a significant cause of mortality among injection drug users (IDUs) in the United States (US). Opiate overdose can be reversed by administering naloxone, an opiate antagonist. Among IDUs, prevalence of witnessing overdose events is high, and the provision of take-home naloxone to IDUs can be an important intervention to reduce the number of overdose fatalities. The Drug Overdose Prevention and Education (DOPE) Project was the first naloxone prescription program (NPP) established in partnership with a county health department (San Francisco Department of Public Health), and is one of the longest running NPPs in the USA. From September 2003 to December 2009, 1,942 individuals were trained and prescribed naloxone through the DOPE Project, of whom 24% returned to receive a naloxone refill, and 11% reported using naloxone during an overdose event. Of 399 overdose events where naloxone was used, participants reported that 89% were reversed. In addition, 83% of participants who reported overdose reversal attributed the reversal to their administration of naloxone, and fewer than 1% reported serious adverse effects. Findings from the DOPE Project add to a growing body of research that suggests that IDUs at high risk of witnessing overdose events are willing to be trained on overdose response strategies and use take-home naloxone during overdose events to prevent deaths.

Seroconversion following nonoccupational postexposure prophylaxis against HIV

BACKGROUND The efficacy of antiretroviral postexposure prophylaxis (PEP) against infection with human immunodeficiency virus (HIV) following occupational exposures has prompted the use of PEP after nonoccupational exposures. There are, however, important differences between occupational and nonoccupational exposures, and the effectiveness of PEP following nonoccupational exposure is unknown. We sought to describe the occurrence and circumstances of HIV seroconversion following nonoccupational PEP. METHODS HIV uninfected individuals reporting potential sexual or injection drug use exposures to HIV in the preceding 72 h received a 28-day regimen of antiretroviral therapy and counseling in a nonrandomized trial. The level of HIV antibody was measured 12 weeks after PEP initiation. RESULTS Of 877 exposed subjects, 702 were evaluable 12 weeks after exposure. Seroconversion was detected in 7 subjects (1%; 95% confidence interval, 0.4%-2%). Three seroconverters reported having no exposures after PEP initiation and, thus, probably represent evidence of chemoprophylactic failure. In the other 4 subjects, additional exposures to HIV after PEP initiation or detection of HIV RNA in plasma specimens obtained at baseline precluded determination of the source of seroconversion. No exposure source was available to assess genetic concordance with the seroconverters virus. CONCLUSIONS As for occupational exposure, PEP is not completely effective in preventing HIV infection following nonoccupational exposure. Therefore, primary prevention remains essential. In contrast to the occupational setting, the potential source of exposure is rarely available for testing in the nonoccupational setting, and exposures are often not isolated. Thus, it is often impossible to determine whether seroconversion resulted from failure of PEP or from other exposures, posing difficulties for future comparative studies seeking to evaluate the effectiveness of PEP.

Postexposure prophylaxis for human immunodeficiency virus (HIV) infection following sexual assault

Although the 1998 Centers for Disease Control and Preventions guidelines for treatment of sexually transmitted diseases recommend offering postexposure prophylaxis for human immunodeficiency virus (HIV) infection following sexual assault, there are no detailed protocols on how to provide this treatment. Postexposure prophylaxis has been shown to lower the risk of seroconversion following occupational exposure to HIV by 81%, but has not yet been evaluated following sexual exposure. Though scientific data are limited, victims of sexual assault should be given the best information available to make an informed decision regarding postexposure prophylaxis. When the choice is made to take medications to prevent HIV infection, treatment should be initiated as soon as possible, but no later than 72 hours following the assault, and should be continued for 28 days. HIV postexposure prophylaxis should be provided in the context of a comprehensive treatment and counseling program that recognizes the physical and psychosocial trauma experienced by victims of sexual assault.

Public Health Care Utilization in a Cohort of Homeless Adult Applicants to a Supportive Housing Program

Supportive housing is subsidized housing with on-site or closely linked services for chronically homeless persons. Most literature describing the effects of supportive housing on health service utilization does not describe use across multiple domains of services. We conducted a retrospective cohort study of 249 applicants to a supportive housing program; 114 (45.7%) were housed in the program. We describe the pattern of service use across multiple domains (housing, physical health care, mental health care, substance abuse treatment). We examine whether enrollment in supportive housing was associated with decreased use of acute health services (emergency department (ED) and inpatient medical hospitalizations) and increased use of ambulatory services (ambulatory medical and generalist care, mental health, and substance abuse treatment) as compared to those eligible but not enrolled. Participants in both groups exhibited high rates of service utilization. We did not find a difference in change in utilization patterns between the two groups [those that received housing (intervention) and those that applied, were eligible, but did not establish residency (usual care group)] comparing the two years prior to the intervention to the two years after. The finding of high rates of maintenance of housing is, in itself, noteworthy. The consistently high use of services across multiple domains and across multiple years speaks to the level of infirmity of this population and the costs of caring for its members.

Impact of housing on the survival of persons with AIDS

BackgroundHomeless persons with HIV/AIDS have greater morbidity and mortality, more hospitalizations, less use of antiretroviral therapy, and worse medication adherence than HIV-infected persons who are stably housed. We examined the effect of homelessness on the mortality of persons with AIDS and measured the effect of supportive housing on AIDS survival.MethodsThe San Francisco AIDS registry was used to identify homeless and housed persons who were diagnosed with AIDS between 1996 and 2006. The registry was computer-matched with a housing database of homeless persons who received housing after their AIDS diagnosis. The Kaplan-Meier product limit method was used to compare survival between persons who were homeless at AIDS diagnosis and those who were housed. Proportional hazards models were used to estimate the independent effects of homelessness and supportive housing on survival after AIDS diagnosis.ResultsOf the 6,558 AIDS cases, 9.8% were homeless at diagnosis. Sixty-seven percent of the persons who were homeless survived five years compared with 81% of those who were housed (p < 0.0001). Homelessness increased the risk of death (adjusted relative hazard [RH] 1.20; 95% confidence limits [CL] 1.03, 1.41). Homeless persons with AIDS who obtained supportive housing had a lower risk of death than those who did not (adjusted RH 0.20; 95% CL 0.05, 0.81).ConclusionSupportive housing ameliorates the negative effect of homelessness on survival with AIDS.

Postexposure Prophylaxis for Human Immunodeficiency Virus Infection after Sexual or Injection Drug Use Exposure: Identification and Characterization of the Source of Exposure

In a nonrandomized study of nonoccupational postexposure prophylaxis (PEP), a cross-sectional evaluation of subjects who were the source of human immunodeficiency (HIV) exposure was performed to characterize partners of index subjects seeking nonoccupational PEP against HIV. Among 401 index subjects, 64 (16%) recruited a source subject. Those in a steady relationship and those who knew that the source subject was HIV antibody positive were more likely to recruit their source subject. Source subjects reported high rates of past (78%) and current (69%) antiretroviral use; 46% of those using antiretroviral drugs had detectable plasma HIV-1 RNA levels. Antiretroviral resistance was detected in many source subjects who reported any use of antiretrovirals and was rare among source subjects who reported no history of antiretroviral use. Clinicians often make treatment decisions on the basis of incomplete knowledge of the source subjects HIV status or antiretroviral treatment history. The treatment history, particularly nonuse of a class of antiretroviral drugs, can be used to predict drug resistance.