M. V. O'shaughnessy

Risky sexual behaviours among injection drugs users with high HIV prevalence: implications for STD control

Injection drug use is inextricably linked to commercial sex work and the transmission of sexually transmitted disease (STD). In many communities prevention efforts have been stalled owing to the marginal existence of this community. This study describes the sexual activities, condom use, reported STDs, and commercial sex work in a large cohort of injection drug users. Seventy two per cent of male and 92% of female subjects in the cohort were sexually active. Among female subjects, 57% reported more than 100 lifetime partners. Condoms were generally not used with regular partners, used about half the time with casual partners, and used about 80% of the time with paying partners. Female sex workers were more likely to have unstable housing and to report incarceration in the previous six months. Reducing the transmission of STDs and HIV in drug using communities is a public health priority. While existing prevention programmes should be strengthened, innovative approaches to STD surveillance, diagnosis, and prevention are needed.

Lower socioeconomic status and shorter survival following HIV infection

We studied the association between socioeconomic status and survival in a prospective study of 364 HIV-infected homosexual men who were recruited during 1982-84. The participants were divided by annual income; those earning above Canadian

Rectal gonorrhoea as an independent risk factor for HIV infection in a cohort of homosexual men.

10,000 (high-income; n = 274) and those below

Prevalence of primary HIV drug resistance among seroconverters during an explosive outbreak of HIV infection among injecting drug users.

10,000 (low-income; n = 90) at recruitment. The latter threshold closely approximated to the poverty level for this population. Low income men were significantly younger than high income men but the groups were similar with respect to baseline CD4 counts, subsequent use of anti-retrovirals and prophylaxis against Pneumocystis carinii pneumonia (PCP), and number of visits attended during follow-up. Subjects were followed for a median of 9.5 years (range 1.8-13.1). By Dec 31, 1993, there were 135 deaths yielding a cumulative mortality rate of mean 45% (SD 4.0) at 11.5 years. Men aged 30 or more at infection had poorer survival than those under 30 (mortality risk ratio 1.56; 95% CI 1.09-2.24; p = 0.015), and longer survival was significantly associated with a higher CD4 count at the earliest seropositive visit. The age-adjusted mortality risk ratio for low income men compared with high income men was significantly increased at 1.63 (95% CI 1.11-2.40; p = 0.013). The significant risk of death for low income men persisted despite adjustment for age at infection, CD4 count, use of zidovudine, dideoxyinosine, and dideoxycytidine, use of PCP prophylaxis, and year of infection. We cannot attribute our findings to income loss as a result of more rapid HIV progression because the same effect was present in people who provided income data before seroconversion. Similarly, our findings are not due to differential access to care because the study was done within the context of a universal health care system, and the two income groups received treatments equally. This finding is consistent with the association of lower socioeconomic status with increased morbidity and mortality observed within large populations and in other diseases.

Progression to AIDS and predictors of AIDS in seroprevalent and seroincident cohorts of homosexual men.

OBJECTIVE--To determine whether certain sexually transmitted diseases are independent risk factors for HIV transmission in a cohort of homosexual men. METHODS--Eligible cases were identified as those who had seroconverted between November 1982 and November 1990. Two persistently HIV-seronegative control participants were randomly selected for each case from all participants who remained seronegative in November 1990. For cases, risk factor data were taken from an index visit which was defined as the first seropositive visit, while for controls these data were obtained from a matched visit which occurred within two months of the index visit for the corresponding case. Mantel-Haenszel methods and logistic regression were used to compare differences in risk factors for seroconversion between cases and controls. RESULTS--A total of 125 cases and 250 controls were eligible for this study. Cases were significantly more likely to have had reported any gonorrhoea (17% versus 6%; OR = 2.94; 95% CI: 1.51-5.73) or syphilis (7% versus 2%; OR = 3.78; 95% CI: 1.33-10.79) than controls during the seroconversion period. Multivariate logistic regression revealed rectal gonorrhoea to be independently associated with risk of seroconversion (odds ratio = 3.18; p = 0.044), whereas urethral gonorrhoea (p = 0.479) and pharyngeal gonorrhoea (p = 0.434) were not after inclusion of rectal gonorrhoea. In addition, the following variables were also shown to exert an independent effect on seroconversion: frequency of anal intercourse, use of illicit drugs, number of male sexual partners, and lack of a post-secondary education. CONCLUSIONS--In this observational study, rectal gonorrhoea was found to be associated with HIV seroconversion after adjustment for a number of HIV risk factors. We cannot rule out that rectal gonorrhoea was not directly associated with HIV infection but rather with other residual lifestyle factors not fully adjusted for in the analysis. However, the relationship with gonococcal involvement of a specific anatomic site lends support to a biological association between gonorrhoea and HIV infection, rather than to alternative non-biologic explanations. Our findings are consistent with previous studies reporting an association between HIV infection and non-ulcerative sexually transmitted diseases. Such a direct association might be explained by postulating that gonorrhoea results in inflamed rectal mucosa and compromised epithelial integrity, thereby predisposing an individual to subsequent HIV infection.

HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort.

OBJECTIVES This study examined the frequency of transmission of drug resistant HIV in the population of injecting drug users (IDU) in Vancouver, Canada during a period of particularly high virus transmission. DESIGN All subjects enrolled in the Vancouver Injection Drug Users Study who seroconverted from HIV negative to positive status (n = 61) between December 1996 and February 1998 were eligible for analysis. The first seropositive sample from 57 individuals with plasma samples available was analyzed for resistance to antiretroviral agents by population based sequencing of the HIV protease and reverse transcriptase genes. METHODS Plasma viral RNA was extracted and the viral reverse transcriptase and protease regions were amplified by nested reverse transcription-PCR. The presence of mutations associated with antiretroviral drug resistance was assessed by automated sequence analysis. RESULTS Protease and reverse transcriptase sequences were successfully obtained from the 57 recent seroconverters. No cases of transmission of variants associated with significant resistance to protease inhibitors or nucleoside and non-nucleosides reverse transcriptase inhibitors were detected. CONCLUSION The frequency of transmission of drug resistant HIV amongst these recently infected IDU is extremely low, with no protease or reverse transcriptase inhibitor resistant strains detected soon after seroconversion. The data provide no rationale for withholding treatment from this already marginalized population.

Quality of life, depression and fatigue among persons co-infected with HIV and hepatitis C: Outcomes from a population-based cohort

As part of an ongoing prospective study of seropositive homosexual men in Vancouver, Canada, a seroprevalent cohort of 246 subjects (i.e. duration of infection unknown) and a seroincident cohort of 102 subjects (i.e. duration of infection known) were followed a median of 63 and 45 months, respectively. Follow-up with validation utilizing record linkage with the Canadian Federal Centre for AIDS registry revealed 58 and nine cases of AIDS in the seroprevalent and seroincident cohorts, respectively, through July 1988. These data yield product limit estimates of the cumulative progression rates to AIDS at 60 months of 23.0% for the seroprevalent cohort, 13.0% for the seroincident cohort, and 21.0% for the combined groups. Univariate analyses revealed the following to be statistically and clinically significant predictors of AIDS progression: low CD4 counts, low CD4/CD8 ratios, elevated immune complexes, elevated immunoglobulin G (IgG) and immunoglobulin A (IgA) levels, and low platelet counts. Cox regression revealed that elevated IgA levels, low CD4 counts, elevated immune complexes, two or more symptoms, and more than 20 male sexual partners in high-risk areas in the 5 years prior to enrollment were independent predictors of progression to AIDS over the subsequent 5 years. A multivariate risk function based on the latter five variables delineated low-, medium- and high-risk groups whose 5-year progression rates to AIDS were 6.7, 15.6 and 64.4%, respectively. The high-risk group contained 75% of all subjects who progressed to AIDS. Only 6% of the high-risk group would have qualified for zidovudine therapy under current guidelines at the beginning of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

The antiviral effect of ritonavir and saquinavir in combination amongst HIV-infected adults: results from a community-based study.

ObjectiveTo assess the effect of baseline HIV reverse transcriptase (RT) and protease sequence variation on virologic outcomes in a large cohort of antiretroviral-naive patients in British Columbia, Canada. MethodsPopulation sequencing of RT and protease was performed on baseline viral RNA of all antiretroviral-naive patients first seeking treatment in British Columbia between June 1997 and August 1998 (n = 479). Relative risks of virological failure associated with genotypic differences from a ‘standard’ HIV strain (HXB2) were assessed for up to 18 months. ResultsThe prevalence of key baseline mutations known to confer resistance to RT and protease inhibitors (PI) was 3.4 and 3.8%, respectively. No statistically significant impact on virologic outcomes could be established for these patients. However, the data suggest that some individuals (harboring a M184V mutation in RT or a V82I in protease) may have benefited from pre-therapy resistance tests. ‘Secondary’ mutations in the protease associated with resistance (e.g. codons 10, 36 or 63) were common, but the presence of these secondary mutations, either alone or in combination, did not appear to result in early loss of therapeutic virological suppression. Preliminary analyses suggest that an amino acid change at codon 35 in the protease may be associated with early treatment failure. ConclusionsThe results suggest that routine genotyping of naive patients about to start antiretroviral therapy would be of benefit to a relatively small proportion of the population. Secondary mutations associated with resistance to PI alone were not found to affect virologic outcomes significantly.

A qualitative investigation into an HIV outbreak among injection drug users in Vancouver, British Columbia

The objective of the study was to describe the additional burden generated by hepatitis C (HCV) infection among HIV-infected individuals as measured by self-reported quality of life, depression and fatigue. The provincial HIV/AIDS Drug Treatment Program (DTP) distributes all antiretroviral medication in the province of British Columbia. Eligibility for accessing antiretrovirals is based on published guidelines commensurate with the International AIDS Society. Each participant is asked to complete a self-administered mailed questionnaire that includes patient sociodemographic information, quality of life measures (Medical Outcomes Study-Short Form (MOS-SF), mental health issues (Centre for Epidemiological Studies Depression scale (CESD) and fatigue information. HIV-HCV co-infected individuals were compared to HIV mono-infected individuals using parametric and nonparametric methods. Multivariate logistic regression was used to examine the impact of hepatitis C on quality of life, depression and fatigue, after controlling for sociodemographics and HIV-specific clinical characteristics. Of the 4,134 individuals who were sent a HIV/AIDS DTP survey in 1999, 2000 or 2001, 484 participants both returned one and had an HCV-antibody test result on file. Of the 484 participants eligible for this analysis, 105 (22%) were HCV-positive. In comparison to the 379 (78%) patients testing negative for HCV, a larger proportion of co-infected patients were female (18% versus 3%, p<0.001), aboriginal (20% versus 3%, p<0.001), had ever injected drugs (79% versus 5%, p<0.001), were unemployed (91% versus 49%, p<0.001) and lived in unstable housing (19% versus 1%, p<0.001) at the time they completed the survey. Co-infected patients reported more symptoms consistent with depression, increased fatigue and poorer quality of life. However, using multivariate modeling, it was determined that the impact of HCV on quality of life, depression and fatigue was better explained by the sociodemographic factors related to poverty and injection drug use, than by HCV itself. In conclusion, individuals co-infected with HIV and HCV represent a patient population with significant physical and mental health challenges. Although these patients experience poorer quality of life, increased depression and fatigue, this experience appears to be primarily related to socio-economic issues rather than HCV infection.

The changing spectrum of AIDS index diseases in Canada

Objective:To characterize the antiviral effect and predictors of response to ritonavir and saquinavir-based antiretroviral combination therapy. Design:Intent-to-treat analysis with suppression of plasma viral load to levels below 2.7 log10 copies/ml as the main outcome measure. Patients:All adult HIV-positive individuals in the province of British Columbia who started taking ritonavir and saquinavir (each at 600 mg twice daily) in combination from 1 September 1996 to 28 February 1997, with a minimum of two plasma viral load measurements, one at baseline and one after the initiation of therapy. Results:A total of 58 participants were prescribed ritonavir and saquinavir. The median plasma viral load at entry was 4.80 log10 copies/ml (interquartile range, 4.51–5.15 log10 copies/ml). A total of 29 (50%) subjects demonstrated a decrease in plasma viral load to levels below 2.7 log10 copies/ml. This level of suppression was associated with higher baseline CD4 cell counts (P = 0.022) and no prior exposure to protease inhibitors (P = 0.001). After controlling for baseline CD4 cell count and plasma viral load, participants naive to protease inhibitors were almost seven times (odds ratio, 6.99; 95% confidence interval, 1.85–26.39; P = 0.004) more likely to suppress their plasma viral load to below 2.7 log10 copies/ml than those who had previously used protease inhibitors. Conclusion:Our analysis demonstrates that a ritonavir and saquinavir-based combination can produce a substantial decrease in plasma viral load with half of the participants decreasing their plasma viral load to below the limit of quantification of the assay. This response, however, is seriously compromised by prior exposure to protease inhibitors.