Neil J. Bodsworth

Response to Hepatitis A Vaccination in Human Immunodeficiency Virus-Infected and - Uninfected Homosexual Men

The influence of human immunodeficiency virus (HIV) infection and vaccination schedule on the immunogenicity of a hepatitis A vaccine was examined. Ninety HIV-infected homosexual men received two vaccinations with hepatitis A vaccine (each 2 mL of 720 ELISA units/mL) either 1 or 6 months apart; 44 HIV-uninfected men received vaccine at study entry and at 6 months. Anti-hepatitis A virus (HAV) titer after vaccination was measured in 83 HIV-positive and 39 HIV-negative men. Seroconversion (anti-HAV antibody > or = 20 IU/L) after two vaccinations occurred more frequently in HIV-negative men (100% vs. 88.2%; P = .03). Anti-HAV titer after two vaccinations was also significantly greater in HIV-negative men (1086 vs. 101 IU/L; P = .0001). HIV-positive men who responded to vaccination had significantly more CD4 lymphocytes (mean, 540/microL) at baseline than those who did not (280/microL; P = .033). Vaccine schedule did not affect response. Vaccination of susceptible patients against HAV should be recommended early in HIV infection using the shorter course to encourage compliance.

Safety and efficacy of nandrolone decanoate for treatment of wasting in patients with HIV infection.

ObjectiveTo evaluate the safety and efficacy of the anabolic steroid, nandrolone decanoate (Deca Durabolin) in patients with HIV wasting who are resistant to nutritional intervention. DesignA 16-week open trial with subjects who had lost 5–15% of their usual body weight. SettingHIV/AIDS specialist ambulatory care services, both public and private, in Sydney, Australia. ParticipantsTwo hundred and twenty men entered the pre-therapy phase, and of these, 24 failed to gain weight and were enrolled. Seventeen subjects (81%) completed the 16-week trial. InterventionsPre-therapy nutritional assessment and education was conducted by the clinical dietitian. Those who failed to gain weight (10.9%) were treated with nandrolone decanoate (100 mg/ml) by deep intramuscular injection every 2 weeks for 16 weeks. Main outcome measuresChanges in weight and body composition (lean body mass, total body water and nitrogen index) were measured by anthropometry, bioelectrical impedance, and in vivo neutron activation. Changes in quality of life were assessed by the 30-item Medical Outcomes Study short form questionnaire. Changes in biochemistry, haematology and immunology were also measured. ResultsThere were significant increases in weight (mean, 0.14 kg per week; P < 0.05) and lean body mass (mean, 3 kg by anthropometry; P < 0.005). The change in lean body mass was of similar magnitude across all measurement modalities. Quality of life parameters, especially functionality, increased significantly during the trial. No subject experienced toxicity. ConclusionNandrolone decanoate has beneficial effects on weight, lean body mass and quality of life in selected patients who have mild to moderate HIV wasting.

Response to hepatitis B vaccination in a primary care setting : Influence of HIV infection, CD4+ lymphocyte count and vaccination schedule

Factors affecting the response to hepatitis B vaccination in a primary care setting were examined by means of a review of case notes of patients attending 22 sexually transmissible disease services. Where not available from the notes, presence of antibody to hepatitis B surface antigen (anti-HBs) was determined by testing available stored serum. One hundred and ninety-five patients completed a course of 3 injections and had an anti-HBs assay performed. The highest response rate (anti-HBs > or = 10 IU/L) was found in human immunodeficiency virus (HIV)-negative heterosexual women (16 of 17, 94.1%) followed by HIV-negative heterosexual men (11 of 12, 91.7%); HIV-negative homosexual men (105 of 120, 87.5%); and HIV-positive homosexual men (6 of 14, 42.9%). (For HIV-positive vs HIV-negative homosexual men, P = 0.0003). Eleven of 14 (78.6%) homosexual men of unknown HIV status responded to vaccination. There was a trend to lower CD4+ lymphocyte counts among HIV-infected patients who responded to hepatitis B vaccination (mean 482 cells/cm2) when compared to those that did not respond (632 cells) but this difference was not statistically significant (P = 0.330). Neither the type of vaccine (recombinant, plasma-derived or mixed) nor the length of vaccination course (mean 6.2 months; range 2 to 18) affected response. This study confirmed that vaccination against hepatitis B is much less effective in HIV-infected homosexual men and marginally less effective for HIV-negative homosexual men, though the mechanism for this reduced response is uncertain. Reassuringly vaccine response was not affected by common variables in primary care settings such as vaccine type or delays in the vaccine schedule.

Hepatitis C virus infection in a large cohort of homosexually active men : independent associations with HIV-1 infection and injecting drug use but not sexual behaviour

OBJECTIVE: To determine the prevalence and risk factors for hepatitis C virus (HCV) infection in a cohort of homosexually active men, with particular reference to assessing sexual transmission. DESIGN: Prevalence based on cross-sectional testing for HCV (c100 protein) antibody in a cohort using sera stored between 1984 and 1989, and assessment of risk factors using a case-control analysis based on questionnaire data from HCV positive and negative subjects. SUBJECTS/SETTING: 1038 homosexually active men who were participating in a prospective study established to identify risk factors for AIDS. They had been recruited through private and public primary care and sexually transmissible disease (STD) services in central Sydney. MAIN OUTCOME MEASURES: Prevalence of HCV antibody and its association with human immunodeficiency virus type 1 (HIV-1) infection and other STDs, number of sexual partners, sexual practices and recreational drug use. RESULTS: Overall, 7.6% of subjects tested were seropositive for HCV antibody. In univariate analysis, HCV infection was significantly associated with injecting drug use (IDU) (OR = 8.18, p < 0.0001) and HIV infection (OR = 3.14, p < 0.0001) and with self reported history of syphilis (OR = 1.88, p = 0.016), anogenital herpes (OR = 1.93, p = 0.017), gonorrhoea (OR = 2.43, p = 0.009) and hepatitis B (OR = 1.92, p = 0.010). In case control analysis, similar sexual behaviours (partner numbers and practices) were reported by HCV positive and HCV negative subjects except that HCV negative subjects more frequently reported engaging than HCV positive subject in unprotected receptive anal intercourse without ejaculation (OR = 0.61, p = 0.034), unprotected insertive (OR = 0.59, p = 0.039) and receptive (OR = 0.56, p = 0.016) oro-anal intercourse (rimming) and insertive fisting (OR = 0.48, p = 0.034). In multiple logistic regression analyses, only HIV-1 infection (OR = 3.18, p < 0.0001) and IDU in the previous six months (OR = 7.24, p < 0.0001) remained significantly associated with the presence of HCV antibody. CONCLUSIONS: IDU was the major behavioural risk factor for HCV infection. If sexual or another from of transmission did occur, it may have been facilitated by concurrent HIV-1 infection.

Phase III Vehicle-Controlled, Multi-Centered Study of Topical Alitretinoin Gel 0.1% in Cutaneous AIDS-Related Kaposi’s Sarcoma

ObjectiveThis randomized, double-blind and vehicle-controlled phase III study was conducted to evaluate the efficacy and safety of alitretinoin gel 0.1% for the topical treatment of the cutaneous lesions of AIDS-related Kaposi’s sarcoma (KS).MethodsPatients received treatment with alitretinoin gel (n = 62) or vehicle gel (n = 72) twice daily for 12 weeks. The primary efficacy endpoint was the cutaneous KS tumor response rate according to AIDS Clinical Trials Group (ACTG) objective criteria applied to topical therapy, with the patient as the unit of analysis.ResultsTreatment of patients with alitretinoin gel resulted in a significant antitumor effect. The overall patient response rate (complete plus partial response) was 37% (23 of 62) for the alitretinoin-treated patients and 7% (5 of 72) for the vehicle-treated patients (p = 0.00003). The difference in response rates for the 2 treatment groups remained significant even after taking into consideration numerous variables, including age (p = 0.00001), Eastern Cooperative Oncology Group (ECOG) status (p = 0.00002), CD4+ cell count (p = 0.00002), history of opportunistic infection (p = 0.00002), aggregate area of indicator lesions (p = 0.00005), number of raised indicator lesions (p = 0.00002), prior therapy for KS (p = 0.00003), and number of drugs (p = 0.00002) used in concomitant antiretroviral therapy. Generally, treatment with alitretinoin gel was well tolerated. The overall incidence of adverse events was similar for the 2 treatment groups. Adverse events related to treatment with alitretinoin gel tended to be mild to moderate in severity and limited to the site of application. The most frequent adverse event occurring at the application site following alitretinoin gel treatment was irritation coded as rash (32%).ConclusionsThe results of this study provide convincing evidence of the superiority of alitretinoin gel over vehicle gel for the treatment of the cutaneous lesions of AIDS-related KS.

Male circumcision and common sexually transmissible diseases in a developed nation setting.

OBJECTIVE--To determine whether the circumcision status of men affected their likelihood of acquiring sexually transmissible diseases (STDs). DESIGN--A cross-sectional study employing an anonymous questionnaire, clinical examination and type specific serology for herpes simplex virus type 2 (HSV-2). SETTING--A public STD clinic in Sydney, Australia. SUBJECTS--300 consecutive heterosexual male patients. MAIN OUTCOME MEASURES--Associations between circumcision status and past or present diagnoses of STDs including HSV-2 serology and clinical pattern of genital herpes. RESULTS--185 (62%) of the men were circumcised and they reported similar ages, education levels and lifetime partner numbers as men who were uncircumcised. There were no significant associations between the presence or absence of the male prepuce and the number diagnosed with genital herpes, genital warts and non-gonococcal urethritis. Men who were uncircumcised were no more likely to be seropositive for HSV-2 and reported symptomatic genital herpes outbreaks of the same frequency and severity as men who were circumcised. Gonorrhoea, syphilis and acute hepatitis B were reported too infrequently to reliably exclude any association with circumcision status. Human immunodeficiency virus infection (rare among heterosexual men in the clinic) was an exclusion criterion. CONCLUSIONS--From the findings of this study, circumcision of men has no significant effect on the incidence of common STDs in this developed nation setting. However, these findings may not necessarily extend to other setting where hygiene is poorer and the spectrum of common STDs is different.

The effect of immunization with inactivated hepatitis A vaccine on the clinical course of HIV-1 infection : 1-year follow-up

Objective:To determine the long-term safety of inactivated hepatitis A virus (HAV) vaccine in men infected with HIV-1. Design:A 1-year prospective case-control study. Setting: Targeted primary care and sexually transmitted diseases clinics. Patients: Ninety HIV-1-positive patients who participated in an earlier efficacy study of HAV vaccination. Controls:Ninety HIV-1-positive men, matched for CD4+ lymphocyte percentage at baseline, who did not receive HAV vaccine. Intervention:All cases were assigned to receive two intramuscular doses of 1440 enzyme-linked immunosorbent assay units of inactivated HAV vaccine (Havrix) either 1 or 6 months apart. Main outcome measures:Development of AIDS, survival, and T-cell subsets after 1 year of follow-up. Results:No significant differences were seen between cases and control for the development of AIDS (10.1 versus 10.7%), deaths (7.3 versus 7.6%) nor for mean decline in circulating CD4+ lymphocyte count (125 versus 123×106/l) after 1 year. Conclusions:Vaccination against HAV appears to be safe in the longer term for HIV- 1-infected men.

Gynaecomastia associated with saquinavir therapy.

Basil Donovan FACSHP FAFPHM, Neil J Bodsworth MD FACSHP, Brian P Mulhall MPH FACSHP1,2,4 and Debbie Allen MBChB FACSHP 1Sydney Sexual Health Centre, Sydney Hospital, PO Box 1614, Sydney NSW, 2Department of Public Health and Community Medicine, University of Sydney, NSW, 3Taylor Square Private Clinic, Sydney, NSW and 4Holden Street Centre, Sexual Health Service, Gosford Hospital, Gosford, NSW, Australia

Randomized, placebo-controlled, phase I/IIa evaluation of the safety and immunogenicity of fowlpox virus expressing HIV gag-pol and interferon-gamma in HIV-1 infected subjects.

We conducted a randomised, placebo-controlled double-blind trial to examine the safety and immunogenicity of a candidate HIV therapeutic vaccine based upon a recombinant fowl pox virus capable of co-expressing the human cytokine interferon-gamma and/or genes from HIV-1. Thirty-five eligible subjects were randomised (12 placebo, 11 fowlpox + HIV genes, 12 fowl pox + HIV genes + interferon-?). All but one subject (placebo group) received three immunizations (by intramuscular injection on day 0, week 4 and week 12) and all completed 52 weeks of follow-up. All subjects continued to take combination antiretroviral therapy for the duration of study. There were no significant toxicity or safety concerns and the distribution of adverse events and their severity was consistent across each randomly assigned vaccine group. Comparison of placebo recipients with the combined recipients of the two vaccine constructs, in terms of anti-HIV gag ELISpot or lymphoproliferative responses, tended to favour the placebo group, but were not significantly different (difference in time-weighted mean change from baseline = 56 Spot forming units (sfu)/106 PBMC; p = 0.062 and 4.4 SI; p = 0.337). There were no significant changes in CTL responses by standard Cr51 release assay. Anti-FPV antibodies were detected by week 14 in 0 placebo and 20 (87%) vaccine recipients. Although safe, neither vaccine construct appeared to possess detectable T-cell mediated anti-HIV immunogenic properties in HIV infected individuals, as measured by standard T cell assays.

2-day versus 5-day famciclovir as treatment of recurrences of genital herpes: results of the FaST study

Background: The brief period of viral replication in recurrent genital herpes lesions suggests shorter therapeutic regimens may be as effective as standard 5-day courses. Objective: To demonstrate that a 2-day course of famciclovir 500 mg statim, then 250 mg twice daily was non-inferior to the standard 5-day course of 125 mg twice daily. Methods: Patients were randomly assigned either the 2-day or 5-day famciclovir course and initiated therapy within 12 h of onset of prodromal symptoms. They were instructed to complete daily questionnaires on herpes-related symptoms and functioning and to attend the clinic for assessment of healing 5.5 days after initiating therapy. Results: A total of 873 patients were randomised at least once and 1038 recurrences were treated. The proportion of evaluable recurrences with lesions present at 5.5 days was less in the 2-day arm (24%) than in the 5-day (28%) arm. The upper 97.5% confidence limit (CL) for this difference in favour of the 2-day arm was 2% in favour of the 5-day arm, well within the 10% predefined for non-inferiority. The upper 97.5% CL was similar in the intent-to-treat, evaluable and per-protocol recurrence populations and when adjusted for baseline differences (in gender, age, herpes history and HIV infection) or for clustering of recurrences within patients. Both treatments had similar side-effects; proportion of lesions aborted; time to next recurrence; patient-reported symptoms; and impact on daily functioning. Conclusions: The 2-day course was as safe and effective as the standard 5-day course and can only enhance patient convenience and compliance.