Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs

Background

Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, we sought to examine whether use of this illicit drug has become a risk factor for HIV infection.

Methods

We included data from people participating in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrolment, lived in the greater Vancouver area, were HIV-negative at enrolment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, we used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996–Nov. 30, 1999 (period 1), Dec. 1, 1999–Nov. 30, 2002 (period 2), and Dec. 1, 2002–Dec. 30, 2005 (period 3).

Results

Overall, 1048 eligible injection drug users were included in our study. Of these, 137 acquired HIV infection during follow-up. The mean proportion of participants who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, we found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57–1.85; period 2: HR 1.68, 95% CI 1.01–2.80; and period 3: HR 2.74, 95% CI 1.06–7.11).

Interpretation

Smoking of crack cocaine was found to be an independent risk factor for HIV seroconversion among people who were injection drug users. This finding points to the urgent need for evidence-based public health initiatives targeted at people who smoke crack cocaine.People who inject illegal drugs are known to be at heightened risk of HIV infection and other blood-borne diseases. In 2007, more than 20% of all new cases of HIV infection recorded in Canada were attributed to injection drug use.¹ Behaviours associated with the use of particular injection drugs (e.g., cocaine and heroin) have been identified as key factors driving HIV transmission among drug users in various settings.² However, over the last decade, significant changes in the popularity of specific illegal drugs have been observed.^3,4 In recent years, cities across Canada have experienced an explosive increase in the use of crack cocaine, whereas some drugs, including heroin, appear to be less commonly used.^5–7 The proportion of drug users who smoke crack cocaine and are homeless or have marginal housing has recently been reported to be as high as 86.6% in Vancouver, 66.7% in Edmonton and 62.4% in Toronto.⁸In the United States, a seminal cross-sectional study involving inner-city young adults showed that smoking of crack cocaine was associated with HIV infection.⁹ However, in Canada, despite the documentation of changing patterns of drug use in many communities,⁸ little is known about the impact that increased smoking of crack cocaine has had on the HIV epidemic. This is problematic because public health programs for people who smoke crack cocaine have been highly controversial in Canada.⁶ We conducted a longitudinal study to evaluate whether smoking of crack cocaine has emerged as a risk factor for HIV infection among people who inject drugs.     

Role of community pharmacies in prevention of AIDS among injecting drug misusers: findings of a survey in England and Wales.

OBJECTIVE--To determine the current and potential roles of community pharmacists in the prevention of AIDS among misusers of injected drugs. DESIGN--Cross sectional postal survey of a one in four random sample of registered pharmacies in England and Wales. SETTING--Project conducted in the addiction research unit of the Institute of Psychiatry, London. SUBJECTS--2469 Community pharmacies in the 15 regional health authorities in England and Wales. MAIN OUTCOME MEASURES--Willingness of pharmacists to sell injecting equipment to known or suspected misusers of drugs; pharmacists'' attitudes to syringe exchange schemes, keeping a "sharps" box for use by misusers of drugs, and offering face to face advice and leaflets; and opinions of community pharmacists on their role in AIDS prevention and drug misuse. RESULTS--1946 Questionnaires were returned, representing a response rate of 79%. This fell short of the target of one in four pharmacies in each family practitioner committee area in England and Wales, and total numbers of respondents were therefore weighted in inverse proportion to the response rate in each area. The findings disclosed a substantial demand for injecting equipment by drug misusers. After weighting of numbers of respondents an estimated 676 of 2434 pharmacies were currently selling injecting equipment and 65 of 2415 (3%) were participating in local syringe exchange schemes; only 94 of 2410 pharmacies (4%) had a sharps box for used equipment. There was a high degree of concern among pharmacists about particular consequences of drug misusers visiting their premises, along with a widespread acceptance that the community pharmacist had an important part to play. CONCLUSIONS--Promoting the participation of community pharmacists in the prevention of AIDS among misusers of injected drugs is a viable policy, but several problems would need to be overcome before it was implemented.     

Progression of HIV disease in a haemophilic cohort followed for 11 years and the effect of treatment.

OBJECTIVE--To describe the progression of HIV disease in a haemophilic cohort and to show the influence of treatment. DESIGN--11 year longitudinal clinical and laboratory study. SETTING--A haemophilia centre. PATIENTS--111 patients infected with HIV during October 1979 to July 1985. MAIN OUTCOME MEASURES--Symptoms of HIV infection, AIDs, and death. INTERVENTIONS--26 asymptomatic patients started taking zidovudine or placebo (1000 mg/day) during November 1988 to February 1990; 10 patients with CD4+ counts of 0.2 x 10(9)/l started zidovudine 500 mg/day during January to November 1990. 35 patients used pentamidine for primary or secondary prophylaxis. RESULTS--At 11 years from seroconversion the estimated rate of progression to AIDS was 42% (95% confidence interval 27% to 57%); to symptoms 85% (75% to 95%); and to death 41% (25% to 57%). Progression to AIDS was significantly faster in patients aged 25 and over than in those aged less than 25 (relative risk 5.0 (2.4 to 10.4); p less than 0.00001) and in those with previous cytomegalovirus infection than in those not infected (relative risk 3.0 (1.4 to 6.8); p = 0.006). 16 of 27 (59%) patients with p24 antigenaemia developed AIDS compared with 17 of 84 (20%) patients without p24 antigen (p less than 0.001). The risk of progression to AIDS before 30 November 1988 in patients with CD4+ counts less than or equal to 0.2 x 10(9)/l was higher than after November 1988 (relative risk 1.9 (0.85 to 4.43); p = 0.1). For 1989 and 1990 the observed cumulative numbers of AIDS cases (among 81 patients with sufficient CD4+ counts) were 22 and 25 compared with 29 and 37 predicted from the rate of fall of CD4+ counts up to the end of 1988 (p = 0.03). CONCLUSION--Treatment seems to be reducing the progression of HIV disease in this haemophilic cohort.     

Modification of hepatic microsomal oxidative drug metabolism in rats by the opiate maintenance drugs acetylmethadol, propoxyphene, and methadone.

The formation of cytochrome P-450 “metabolic intermediate” complexes $\text{in}$$\text{vivo}$ occurred with acetylmethadol and propoxyphene, but not methadone in both naive and phenobarbital-induced animals. The $\text{in}$$\text{vivo}$ formation correlated with the relative ability of these three compounds to form metabolic intermediate complexes and inhibit mixed-function oxidation reactions $\text{in vitro}$.     

Outbreak of HIV infection in a Scottish prison.

OBJECTIVE--To investigate the possible spread of HIV infection and its route of transmission among prison inmates. DESIGN--In response to an outbreak of acute clinical hepatitis B and two seroconversions to HIV infection, counselling and testing for HIV were offered to all inmates over a two week period in July 1993. Information was sought about drug injecting, sexual behaviour, and previous HIV testing. SETTING--HM Prison Glenochil in Scotland. SUBJECTS--Adult male prisoners. MAIN OUTCOME MEASURES--Uptake of HIV counselling and testing; occurrence and mode of HIV transmission within the prison. RESULTS--Of a total 378 inmates, 227 (60%) were counselled and 162 (43%) tested for HIV. Twelve (7%) of those tested were positive for antibody to HIV. One third (76) of those counselled had injected drugs at some time, of whom 33 (43%) had injected in Glenochil; all 12 seropositive men belonged to this latter group. Thirty two of these 33 had shared needles and syringes in the prison. A further two inmates who injected in the prison were diagnosed as positive for HIV two months previously. Evidence based on sequential results and time of entry into prison indicated that eight transmissions definitely occurred within prison in the first half of 1993. CONCLUSION--This is the first report of an outbreak of HIV infection occurring within a prison. Restricted access to injecting equipment resulted in random sharing and placed injectors at high risk of becoming infected with HIV. Measures to prevent further spread of infection among prison injectors are urgently required.     

Risk of HIV infection from transfusion with blood negative for HIV antibody in a west African city.

OBJECTIVE--To estimate the risk of infection with HIV (HIV 1 or HIV 2, or both) from transfusion of a screened unit of blood in a high prevalence area in west Africa. DESIGN--Retrospective cohort study for January-July 1991. SETTING--National Blood Transfusion Centre, Abidjan, Côte d''Ivoire. SUBJECTS--Repeat donors (5831 units of blood) and first time donors (5076 units) in the first five months of 1991. MAIN OUTCOME MEASURES--Prevalence and estimated incidence of HIV infection in repeat and first time donors; estimated rate of potentially infected, HIV antibody negative units; and rate of (false negative) potentially infected units assuming a laboratory test sensitivity of 99%. RESULTS--Overall HIV prevalence was 11.0% in first time donors and 2.1% in repeat donors. In the first seven months of 1991, 29 HIV antibody positive (27 HIV 1, 1 HIV 2, 1 dually reactive) donors with a seronegative unit of blood earlier in the year were identified; 26 had donated blood eight weeks or less before their estimated dates of seroconversion and may have been infectious (minimum rate 26/5831 (4.5/1000 potentially infected units)). Estimated incidence of infection in repeat donors was 1.2-2.5%. Laboratory test insensitivity would result in an estimated 1.1/1000 false negative units from first time donors and 0.2/1000 units from regular donors. The overall rate of potentially infected units (all donors, seroconversions, and errors) was estimated at 5.4-10.6/1000. CONCLUSIONS--The risk of HIV infection from a single unit of blood remains substantial (5.4-10.6/1000 units). To prevent infection from blood transfusion in areas of high incidence and prevalence of HIV all but absolutely essential transfusions should be avoided, and donors with low incidence of HIV infection should be selected.     

Manifestations of immune deficiency in children with perinatal HIV infection in the treatment dynamics

Clinical and immunological parameters in the children with perinatal HIV infection were investigated in the dynamics of the long-term prospective observation. It was revealed, that all the HIV infected children had clinical signs of immunodeficiency and laboratory signs of combined damage of the immune system. The complex of therapeutic measures, including antiretroviral therapy, prevention of opportunistic and acute respiratory infections, rational immunotherapy to stimulate production of endogenous interferon and normalization of the balance of cytokines significantly reduced the frequency of the clinical manifestations of the infectious syndrome and improved the patients resistance to infections.     

Opportunistic infection as a cause of transient viremia in chronically infected HIV patients under treatment with HAART

When highly active antiretroviral therapy is administered for long periods of time to HIV-1 infected patients, most patients achieve viral loads that are “undetectable” by standard assay (i.e., HIV-1 RNA < 50 copies/ml). Yet despite exhibiting sustained viral loads below the level of detection, a number of these patients experience unexplained episodes of transient viremia or viral “blips”. We propose here that transient activation of the immune system by opportunistic infection may explain these episodes of viremia. Indeed, immune activation by opportunistic infection may spur HIV replication, replenish viral reservoirs and contribute to accelerated disease progression. In order to investigate the effects of intercurrent infection on chronically infected HIV patients under treatment with highly active antiretroviral therapy (HAART), we extend a simple dynamic model of the effects of vaccination on HIV infection [Jones, L.E., Perelson, A.S., 2002. Modeling the effects of vaccination on chronically infected HIV-positive patients. JAIDS 31, 369–377] to include growing pathogens. We then propose a more realistic model for immune cell expansion in the presence of pathogen, and include this in a set of competing models that allow low baseline viral loads in the presence of drug treatment. Programmed expansion of immune cells upon exposure to antigen is a feature not previously included in HIV models, and one that is especially important to consider when simulating an immune response to opportunistic infection. Using these models we show that viral blips with realistic duration and amplitude can be generated by intercurrent infections in HAART treated patients.     

Comparison of treatment outcome in patients with rheumatoid arthritis treated with TFX- Polfa or gold salts after a one year follow up]

Thirty five patients with rheumatoid arthritis were given TFX Polfa, initially everyday in the intramuscular injections in the dose of 10 mg TFX protein for 60 days, followed by 1 injection of 10 mg TFX protein a week for 10 months. Other 30 patients with rheumatoid arthritis treated with gold salts were used for comparison. Several clinical and laboratory tests were performed before the treatment and after 1 year. A one-year therapy significantly improved all clinical parameters in both groups. A significant increase in hemoglobin and erythrocyte count was noted in patients treated with TFX. A significant decrease in the markers of inflammation was seen. A percentage of both early and delayed E rosettes increased highly significantly. The obtained results suggest that TFX Polfa is efficient in these cases of the rheumatoid arthritis which cannot be treated with gold salts.     

Factors associated with HIV infection in married or cohabitating couples in Kenya: results from a nationally representative study

Background

In order to inform prevention programming, we analyzed HIV discordance and concordance within couples in the Kenya AIDS Indicator Survey (KAIS) 2007.

Methods

KAIS was a nationally representative population-based sero-survey that examined demographic and behavioral indicators and serologic testing for HIV, HSV-2, syphilis, and CD4 cell counts in 15,853 consenting adults aged 15–64 years. We analyzed interview and blood testing data at the sexual partnership level from married or cohabitating couples. Multivariable regression models were used to identify factors independently associated with HIV discordant and concordant status.

Results

Of 3256 couples identified in the survey, 2748 (84.4%) had interview and blood testing data. Overall, 3.8% of couples were concordantly infected with HIV, and in 5.8% one partner was infected, translating to 338,000 discordant couples in Kenya. In 83.6% of HIV-infected Kenyans living in married or cohabitating couples neither partner knew their HIV status. Factors independently associated with HIV-discordance included young age in women (AOR 1.5, 95% CI: 1.2–1.8; p<0.0001), increasing number of lifetime sexual partners in women (AOR 1.5, 95% CI: 1.3–1.8; p<0.0001), HSV-2 infection in either or both partners (AOR 4.1, 95% CI: 2.3–7.2; p<0.0001), and lack of male circumcision (AOR 1.6, 95% CI: 1.0–2.5; p = 0.032). Independent factors for HIV-concordance included HSV-2 infection in both partners (AOR 6.5, 95% CI: 2.3–18.7; p = 0.001) and lack of male circumcision (AOR 1.8, 95% CI: 1.0–3.3; p = 0.043).

Conclusions

Couple prevention interventions should begin early in relationships and include mutual knowledge of HIV status, reduction of outside sexual partners, and promotion of male circumcision among HIV-uninfected men. Mechanisms for effective prevention or suppression of HSV-2 infection are also needed.     

Progression to AIDS in the absence of a gene for vpr or vpx.

Rhesus monkeys (Macaca mulatta) were experimentally infected with strains of simian immunodeficiency virus (SIV) derived from SIVmac239 lacking vpr, vpx, or both vpr and vpx genes. These auxiliary genes are not required for virus replication in cultured cells but are consistently conserved within the SIVmac/human immunodeficiency virus type 2/SIVsm group of primate lentiviruses. All four rhesus monkeys infected with the vpr deletion mutant showed an early spike in plasma antigenemia, maintained high virus burdens, exhibited declines in CD4+ lymphocyte concentrations, and had significant changes in lymph node morphology, and two have died to date with AIDS. The behavior of the vpr deletion mutant was indistinguishable from that of the parental, wild-type virus. Rhesus monkeys infected with the vpx deletion mutant showed lower levels of plasma antigenemia, lower virus burdens, and delayed declines in CD4+ lymphocyte concentrations but nonetheless progressed with AIDS to a terminal stage. The vpr+vpx double mutant was severely attenuated, with much lower virus burdens and no evidence of disease progression. These and other results indicate that vpr provides only a slight facilitating advantage for wild-type SIVmac replication in vivo. Thus, progression to AIDS and death can occur in the absence of a gene for vpr or vpx.