7th Report from: 7th Conference on Retroviruses and Opportunistic Infections San Francisco, Wednesday Feb 2

Post-Exposure Prophylaxis For Sexual and Occupational Exposure 

Following is data from a pilot study of post-exposure prophylaxis given to individuals within 72 hours after non-occupational exposure. Data on PEP for health-care workers with an exposure through for example a needle prick suggests that PEP does help prevent infection. In the San Francisco pilot study described below for non-occupational exposure I think it's difficult to draw conclusions because only 401 subjects enrolled and the rate of infection after exposure can be low. Resistance testing on a small number of exposed individuals found drug resistance, but the number of subjects receiving resistance testing was so small, again it's difficult to draw conclusions.

In the San Francisco study, 401 HIV-exposed subjects enrolled. There were no-seroconversions. Genotypic drug resistance was detected in at least 10/16 subjects. Three individuals had 3 or more AZT mutations.

Despite 59% reporting nausea, headache or fatigue, 80% completed 4 weeks of therapy. Among those still taking therapy at mid-point of study, 79% reported complete adherence in prior 4 days

Described below is a PEP program in New York City for adolescants and children exposed to HIV through sexual assault. 15 patients were enrolled. 10 people were eligible because treatment is recommended within 72 hours of exposure and these 5 had been exposed more than 72 hours ago.To date 4/6 kids have completed 6 months of observation and all 4 tested negative at 6 months. 3 patients were 98% compliant and 1 patient elected to discontinue after 14 days.

One likely benefit of these PEP programs is that people who may practice high risk behavior can receive educational interventions that may alter future risky behavior.

In a study of health-care workers described below, the prevalence of resistance mutations and phenotypic resistance were assessed. The incidence of mutations were high. In 6/7 of the patients with genotypic resistance, phenotypic resistance was detected supporting the genotypic analysis. The study concludes that since there were no seroconversions among the health-care workers, the significance of the emergence of drug resistant HIV-1 strains and the implications for PEP are uncertain
Post-Exposure Prophylaxis after Sexual or Drug Use Exposure to HIV: Final Results from the San Francisco Post-Exposure Prevention (PEP) Project.

J. N. MARTIN*, M. E. ROLAND, J. D. BAMBERGER, M. A. CHESNEY, C. WALDO, J. UNICK, C. LAY, M. H. KATZ, T. J. COATES, and J. O. KAHN. Univ. of California, San Francisco and San Francisco Dept. of Publ. Hlth., CA.

Background: The efficacy of PEP following occupational HIV exposure has prompted advocacy for PEP following sexual or drug use exposure to HIV. To date, however, the feasibility of providing PEP after non-occupational exposures in the community has not been determined.

Methods: A feasibility study was performed of PEP in persons reporting sexual (receptive or insertive anal or vaginal intercourse; or receptive oral intercourse with ejaculation), injection drug use, or other non-occupational exposures to HIV within the past 72 hrs. All were offered 4 weeks of antiretroviral therapy, received risk reduction and medication adherence counseling, and were followed at 1, 2, 4, 26, and 52 weeks post-exposure.

Results: In 16 months, 401 participants were enrolled. Sexual exposure was most common (94%), followed by injection drug use (2%), non-volitional needle stick accidents (2%), dual sex and drug use exposure (1%), and assault (1%). Among sexual exposures, receptive anal intercourse was most common (40%). Condoms were not used in the majority of sexual exposures (64%); condom failure occurred less frequently (36%). Nearly half of participants (41%) knew their exposure source was HIV-infected; 55% were unsure of source serostatus but reported the source had an HIV risk factor and 4% did not know source serostatus or risk factor history. All but 5 persons elected to use antiviral therapy; AZT/3TC combination twice daily was most common (88%). Follow-up was 96%, 87%, 86%, 71%, and 68% at 1, 2, 4, 26 and 52 wks respectively. Subjective toxicity was common (59% reported nausea, headache, or fatigue), but 80% completed 4 wks of therapy. At the mid-point of therapy, among those still taking therapy, 79% reported complete adherence in the prior 4 days. No HIV seroconversion attributable to the initial exposure has occurred.

Conclusion: Providing PEP within 72 hours to persons reporting sexual or other non-occupational exposures to HIV and following such persons for up to one year is feasible. Determining the efficacy of PEP and the most cost-efficient mechanism of delivery represents the next challenge.
Who Is the Source of HIV Exposure in the San Francisco Post-Exposure Prevention (PEP) Project?

M. E. ROLAND*^{1}, J. N. MARTIN^{2}, R. M. GRANT^{1}, J. D. BAMBERGER^{3}, T. J. COATES^{2}, M. H. KATZ^{3}, and J. O. KAHN^{1}. ^{1}Univ. of California Positive Hlth. Program at San Francisco Gen. Hosp; ^{2}Ctr. for AIDS Prevention Studies; and ^{3}San Francisco Dept. of Publ. Hlth., CA.

Introduction: 401 index subjects enrolled in the San Francisco PEP Project within 72 hours of a potential high risk sexual or injection drug use exposure to HIV. They received HIV testing, counseling and were offered 28 days of antiviral medications. The source of exposure was evaluated for HIV antibody status, CD4+ T-cell count, HIV-1 RNA level, antiretroviral (ARV) history and drug resistance.

Results: 66 indexes recruited 68 source subjects. There were no significant differences in age, ethnicity, or risk behavior of indexes who did and did not recruit their source. More women recruited sources (34% vs 15%; p=0.02). 31% of indexes who knew their source was HIV positive, vs 6 -12% whose source HIV status was unknown, recruited sources. 52 sources tested HIV antibody positive.

HIV-1 RNA (copies/mL) bDNA (Bayer Quantiplex v.2.0 or 3.0): 40% were undetectable (<50/500 = LOD), 31% had LOD -10,000; 12% had 10,001-30,000; 10% had 30,001-60,000; and 8% had >60,000.

CD4+ T-cell count (cells/mL): 29% had <200, 38% had 200 - 500, and 29% had >500.

ARV History:79% had ever used any ARV, 71% any protease inhibitor (PI) and 23% any non-nucleoside reverse transcriptase inhibitor(NNRTI).

Current ARV Use: 69% were using any ARV, 60% any PI, and 17% any NNRTI. Nucleoside Analogue (NRTI) Use: 62% ever used AZT (21% current); 73% ever used 3TC (48% curr.), 56% ever used D4T (40% curr.); 35% ever used ddI (13% curr.).

Resistance: Genotyping was completed on 16 specimens. Reverse Transcriptase mutations were seen in 10/16, with the number of positive specimens in parentheses: M41L (4), D67L (4), L210W (3), T215Y(5); 3 AZT mutations (3); M184V (7). No NNRTI mutations were seen. Primary Protease (PR) mutations were seen in 6/16, with the number of positive specimens in parentheses: M46I (3), I54V (1), V82A (3), L90M (5). Secondary PR mutations were seen in 15/16.

Discussion: Exposed individuals seeking PEP who knew their source was HIV positive were more likely to bring that person in for testing than those who did not know the source's HIV status. 40% of sources had an undetectable plasma HIV-1 RNA level. HIV positive source subjects were highly ARV experienced, and a significant proportion of treated individuals had resistance mutations to AZT and 3TC, ARVs commonly used for PEP.


Pediatric and Adolescent HIV Prophylaxis after Sexual Assault.

N. NEU*, S. HEFFERNAN, J. BROWN, and M. STIMELL. Columbia Univ. and New York Presbyterian Hosp., NY.

Objective: To develop guidelines for HIV prophylaxis in adolescents following sexual assault.

Methods: From March to October 1999, adolescent patients presenting the New York Presbyterian Hospital ER within 72 hours of sexual assault were evaluated for enrollment in a prospective cohort study. Patients were provided a 28-day course of Combivir" (Glaxo Wellcome, Research Triangle Park, NC) for HIV prophylaxis. Patients were seen within 24 hours by the Pediatric HIV and Child Advocacy teams with follow-up planned after 1, 4-6, 12 and 24 weeks.

Results: 15 patients (13 females/2 males) were evaluated in the pediatric ER for sexual assault. The mean age was 14 years (range 11-19) and 66% were Hispanic. Per the protocol, 10/15 were eligible for HIV prophylaxis. 5 patients were excluded due to presentation at >72 hours (2), pregnancy (1), or chronic history of sexual assault without an acute event (2). Of the 10 eligible patients, 7 enrolled in the study, 2 were lost to follow-up after the ER visit, and 1 refused study. 6/7 enrolled patients were evaluated as 1 was lost to follow-up. 5 presented within 24 hours. The 1 male victim reported both anal and oral intercourse. All of the females reported vaginal intercourse as their exposure except 1 who reported multiple sites of exposure (oral, anal and vaginal). To date, 4/6 completed 6 months of observation. There was 98% compliance with total days of therapy for 3 patients and 1 patient elected to discontinue medication after 14 days. All 4 tested HIV negative at 6 months. Relevant side effects included abdominal pain (1) and a transient decrease in Hct of 4.7% in 3 of 4 patients at 2 weeks that normalized at the end of therapy.

Discussion: A well-structured specialized program to manage sexual assault and providing intensive outreach can assist high-risk patients to receive optimal care. In our study, most patients were compliant with appointments and tolerated Combivir" although there was a trend towards the development of transient anemia.
Prevalence of Drug-Resistant HIV-1 in Patients Who Are the Source of Occupational Exposures to Health Care Workers.

R. CHEINGSONG*, E. BELTRAMI, R. RESPESS, D. CARDO, and the Occupational HIV Exposure Study Group. CDC, Atlanta, GA.

Post-exposure prophylaxis (PEP) with zidovudine (ZDV) and lamivudine (3TC) is currently recommended for certain occupational HIV exposures. Addition of a protease inhibitor (PI) is recommended for exposures that pose an increased risk for HIV transmission or where resistance to antiretroviral agents is known or suspected. Although antiretroviral therapy among persons with HIV has become widely implemented, the spectrum of HIV drug resistance among patients who are the source for occupational exposures to HIV-1 needs further studied. By sequencing, we assessed the prevalence of resistance-associated mutations in 42 HIV-1 infected source patients enrolled at 7 sites in the US between 1998-1999. Of these patients, 20 were drug naive and 22 were drug experienced. Overall, the prevalence of primary mutations associated with resistance to RT inhibitors (RTIs) or PI was high (16/42, 38%). ZDV- and/or 3TC-associated mutations were common (14/16, 88%). Single mutations associated with resistance to 3TC (M184V) were observed in five patients. Two patients had mutations associated with either non-nucleoside RTI (K103N) or PI (L90M) resistance. Nine patients had two or more mutations associated with RTI and/or PI resistance. Seven samples with two or more mutations were phenotyped by recombinant virus assays. Six of them had phenotypic resistance that supported the genotypic analysis. No HIV seroconversions were observed among exposed health care workers. Although the results demonstrate a high proportion of HIV-1 drug resistant strains in the source patients, in particular those who were on therapy, the significance of the emergence of drug resistant HIV-1 strains and the implications for PEP are uncertain.