HIV infection and risk of overdose: a systematic review and meta-analysis

Drug overdose is a common cause of non-AIDS death among people with HIV and the leading cause of death for people who inject drugs. People with HIV are often exposed to opioid medications during their HIV care experience; others may continue to use illicit opioids despite their disease status. In either situation, there may be a heightened risk for nonfatal or fatal overdose. The potential mechanisms for this elevated risk remain controversial. We systematically reviewed the literature on the HIV-overdose association, meta-analyzed results, and investigated sources of heterogeneity, including study characteristics related to hypothesize biological, behavioral, and structural mechanisms of the association. Forty-six studies were reviewed, 24 of which measured HIV status serologically and provided data quantifying an association. Meta-analysis results showed that HIV seropositivity was associated with an increased risk of overdose mortality (pooled risk ratio 1.74, 95% confidence interval 1.45, 2.09), although the effect was heterogeneous (Q = 80.3, P < 0.01, I(2) = 71%). The wide variability in study designs and aims limited our ability to detect potentially important sources of heterogeneity. Causal mechanisms considered in the literature focused primarily on biological and behavioral factors, although evidence suggests structural or environmental factors may help explain the greater risk of overdose among HIV-infected drug users. Gaps in the literature for future research and prevention efforts as well as recommendations that follow from these findings are discussed.     

补体在HIV感染和发病机制中的作用

补体是免疫系统的重要组成成分,在抵制病原体入侵及播散方面起重要作用。但在艾滋病病毒（HIV）的感染和发病机制中,人们发现补体系统在溶解病毒方面只发挥极少的作用,反而在促进病毒侵入机体、储存病毒、增强病毒感染能力方面发挥重要的作用。该文综述了补体在HIV感染和发病机制方面的研究,为探索HIV补体相关免疫治疗提供理论依据。     

The independent effect of drug resistance on T cell activation in HIV infection

OBJECTIVE: Antiretroviral-treated individuals with drug-resistant HIV experience slower CD4 cell count declines than untreated individuals, independent of degree of viremia. As immune activation independently predicts disease progression, we hypothesized that patients with drug-resistant viremia would have less immune activation than patients with wild-type viremia, independent of plasma HIV RNA levels and that these differences would not be explained by a direct drug effect of protease inhibitors. METHODS: Percentages of activated (CD38/HLA-DR) T cells were compared between untreated participants with wild-type viremia and antiretroviral-treated participants with drug-resistant viremia, after adjusting for plasma HIV RNA levels among other factors associated with T cell activation. Changes in T cell activation were also assessed in subjects discontinuing protease inhibitors while continuing other antiretroviral medications. RESULTS: Twenty-one untreated participants with wild-type viremia and 70 antiretroviral-treated participants with drug-resistant viremia were evaluated. Relative to untreated participants, those with drug-resistant viremia had 29% fewer activated CD4 (P = 0.051) and CD8 (P = 0.012) T cells after adjustment for plasma HIV RNA levels among other factors. There was no evidence for an early change in T cell activation among 13 subjects with drug-resistant viremia interrupting protease inhibitors while continuing other antiretroviral medications, but a significant increase in T cell activation with complete or partial emergence of wild-type sequences in protease. CONCLUSIONS: Antiretroviral-treated patients with drug-resistant viremia have less T cell activation than untreated patients, independent of plasma HIV RNA level. Decreased ability of drug-resistant variants to cause T cell activation likely contributes to slower CD4 cell count declines among patients with drug-resistant viremia.     

The impact of HIV infection on adult mortality in some communities in Zambia: a cohort study

Objective  To examine the contribution of human immunodeficiency virus (HIV) to adult death rates between 1995/1996 and 1998/1999 in some urban and rural populations in Zambia.
Method  A cohort of 2592 out of 3013 adults aged 15–49 years enrolled in a baseline survey in 1995/1996 in areas of Chelston Township (HIV prevalence 26.2%) and Kapiri Mposhi district (HIV prevalence 15.6%) were followed up in 1998/1999. Person years of observation (PYO) were calculated for those known to have been alive, dead and migrated between the surveys. Fixed covariates Cox proportional hazard models were fitted to assess survival prospects.
Results  Death rates per 1000 PYO in the rural cohort were 38.1 among those with HIV, 4.8 among those without HIV and 9.8 for all; the population attributable fraction of deaths among those with HIV was 52.3%. Respective estimates in the urban cohort were 53.8, 4.6, 17.2 and 73.6%. The hazard rate (HR) ratio of death for persons infected with HIV was 8.7 times [HR 8.65; 95% confidence interval (CI) 5.28–14.15] higher than for the uninfected after adjusting for age, area of residence, marital status, self-rated health and years spent on education. HR among those who rated their health good/excellent was 40% less, i.e. HR 0.60 (95% CI: 0.40–0.91) than those who rated it to be poor/fair.
Conclusions  HIV infection was the most important factor accounting for adult deaths in the communities.     

The effect of schistosome infection on the mortality rates of Bulinus globosus and Biomphalaria pfeifferi

Schistosoma infections of Bulinus globosus increased the per capita mortality rate in the laboratory from 0.231 to 0.406 per week. Schistosoma mansoni infections of Biomphalaria pfeifferi increased the per capita mortality rate in the laboratory from 0.055 to 0.177 per week. Calculations based on data from previous work by another author indicate an increase in the mortality rate of B. pfeifferi associated with prepatent S. mansoni infection.     

HIV target cells: effect of their infection by HIV on the pathogenesis of AIDS

Pathogenesis of HIV infection and expression of retroviral proteins are gradually being elucidated. Antibody to HIV is a marker of past or present viral infection. The virus can be isolated from cultured lymphocytes of seropositive but not seronegative patients. Sero-epidemiological studies show that the majority of infected patients are asymptomatic carriers without biological sign of immune depression. Some then show immune abnormalities such as a decrease of CD4 cells in the blood; some patients present with lymphadenopathies or signs of AIDS-related complexes. Frank AIDS is a late stage of the disease. Some cofactors increase the immunodeficiency and then accelerate the passage from asymptomatic carrier to persistent generalized lymphadenopathies or AIDS by spreading the virus into target cells, susceptible T4 cells, bone marrow precursors, or brain. These AIDS patients then present with opportunistic infections and/or malignancies like Kaposi's sarcoma, lymphoma, and/or brain diseases (dementia or encephalitis).     

The protective effect of male circumcision on HIV infection in a sample of Kenyan men

This article examines the association between male circumcision and HIV infection in a national sample. The analysis is based on the 2003 Kenya Demographic and Health Survey (KDHS), a nationally representative household-based population survey of adults, in which male respondents self-reported their circumcision status. In addition, in some households eligible for individual interview, blood samples were subsequently anonymously obtained for HIV testing, making this the first study linking socio-demographic information to HIV status at the national level. The study sample is limited to 3 413 men aged 15–54 years who gave valid information on their circumcision and HIV statuses. Nearly 5% of the men were HIV-positive, and 86% had been circumcised. HIV prevalence was significantly higher among the uncircumcised men (12%) than among the circumcised men (3%). This indication of the protective effect of male circumcision on HIV infection remained statistically significant (OR 0.15; 95%CI: 0.09–0.23) even after controlling for the effects of socio-demographic variables, age at first sexual intercourse, and use of paid sex. Based on these results, we recommend that HIV-prevention advocates and activists, scholars, bio-medical communities and political leaders find ways to include this oldest surgical procedure in their HIV/AIDS discourses and programmes in sub-Saharan Africa.     

Markers of atherosclerosis and inflammation and mortality in patients with HIV infection

ObjectiveHIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. Surrogate marker studies suggest an increased prevalence of vascular abnormalities in HIV infection. We examined the association of all-cause mortality in HIV-infected patients with carotid artery intima-media thickness (cIMT) and high-sensitivity C-reactive protein (hsCRP).Design and methodsBaseline risk factors, cIMT and hsCRP were prospectively measured in 327 HIV-infected participants. Follow-up time with median of 3.1 years was calculated from baseline to death or censored dated 7/31/07. Cox Proportional Hazards models were used to study risk factors associated with mortality.ResultsThirty-eight (11.6%) of participants have died since study enrollment. cIMT was significantly higher in those who died and decedents were significantly more likely to have cIMT above the 75th percentile. Those who died had higher hsCRP than those alive and more had hsCRP values above 3 mg/L. CD4 count was lower and log₁₀ viral load was higher in decedents, but antiretroviral regimens were similar in both groups. cIMT and hsCRP levels were significantly associated with mortality (HR = 2.74, 95% CI 1.26–5.97, p = 0.01; HR = 2.38, 95% CI 1.15–4.9, p = 0.02).ConclusionsOur study demonstrated a strong association of carotid IMT and hsCRP with all-cause death in this HIV-infected population despite being similar with respect to exposure to antiretroviral medications. Together these surrogate markers may be indices of chronic inflammation and unfavorable outcomes in HIV-positive patients.     

The impact of HIV infection on tropical diseases

HIV and tropical infections affect each other mutually. HIV infection may alter the natural history of tropical infectious diseases, impede rapid diagnosis, or reduce the efficacy of antiparasitic treatment. Tropical infections may facilitate the transmission of HIV and accelerate progression from asymptomatic HIV infection to AIDS. This article reviews data on known interactions for malaria, leishmaniasis, human African trypanosomiasis, Chagas' disease, schistosomiasis, onchocerciasis, lymphatic filariasis, and intestinal helminthiases.     

The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya

OBJECTIVE: To determine the effect of dual infection with HIV and malaria on birth outcomes and maternal anaemia among women delivering at a large public hospital in Kisumu, western Kenya. SUBJECTS AND METHODS: Data on obstetric and neonatal characteristics, maternal and placental parasitaemia, and postpartum haemoglobin levels were collected from women enrolled in a cohort study of the interaction between malaria and HIV during pregnancy. RESULTS: Between 1996 and 1999, data were available from 2466 singleton deliveries. The maternal HIV seroprevalence was 24.3%, and at delivery 22.0% of the women had evidence of malaria. Low birthweight, preterm delivery (PTD), intrauterine growth retardation (IUGR) and maternal anaemia (haemoglobin < 8 g/dl) occurred in 4.6, 6.7, 9.8 and 13.8% of deliveries, respectively. Maternal HIV, in the absence of malaria, was associated with a 99 g (95% CI 52-145) reduction in mean birthweight among all gravidae. Malaria was associated with both IUGR and PTD, resulting in a reduction in mean birthweight of 145 g (95% CI 82-209) among HIV-seronegative and 206 g (95% CI 115-298) among HIV-seropositive primigravidae, but not among multigravidae. Both HIV and malaria were significant risk factors for postpartum maternal anaemia, and HIV-seropositive women with malaria were twice as likely to have anaemia than HIV-seronegative women with or without malaria. CONCLUSION: Women with dual infection are at particular risk of adverse birth outcomes. In areas with a moderate or high prevalence of HIV and malaria, all pregnant women should be the focus of malaria and anaemia control efforts to improve birth outcomes.