Change in atherosclerosis progression in HIV-infected patients: ANRS Aquitaine Cohort, 1999-2004

This study reported the changes in carotid intima-media thickness (IMT) during a 36-month period in 233 HIV-infected patients. Median IMT increased in the first 12 months and then decreased by month 36. The prevalence of treatment with lipid-lowering agents and protease inhibitor-free highly active antiretroviral therapy regimens increased, whereas smoking prevalence decreased. The progression of atherosclerosis in HIV-infected patients can be controlled. The impact of individual measures to reduce the cardiovascular risk should be evaluated further.     

Interaction between HIV-1 and HCV infections: towards a new entity?

Since human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same modes of transmission, HIV-HCV co-infected patients are relatively common. Until recently, the clinical course of HCV in co-infected patients was overshadowed by the high morbidity and mortality of HIV disease. Recent reductions in morbidity and mortality among HIV-infected patients due to the advent of highly active antiretroviral therapy (HAART), have contributed to the emergence of HCV as a significant viral pathogen in this population. This article reviews the current evidence on the epidemiology and clinical implications of an interaction between HIV-1 and HCV infections.     

Glucose ingestion induces an increase in intranuclear nuclear factor kappaB, a fall in cellular inhibitor kappaB, and an increase in tumor necrosis factor alpha messenger RNA by mononuclear cells in healthy human subjects

Because hyperglycemia is a major detrimental factor in the prognosis of acute cardiovascular conditions such as acute myocardial infarction (AMI) and stroke, and because an acute glucose challenge in healthy subjects has been shown to induce oxidative stress in mononuclear cells (MNCs), we have now investigated whether glucose induces inflammatory stress at the cellular and molecular level. Glucose ingestion (75 g in 300 mL water) in healthy human subjects resulted in an increase in intranuclear nuclear factor kappaB (NF-kappaB) binding, the reduction of inhibitor kappaB alpha (IkappaBalpha) protein, and an increase in the activity of inhibitor kappaB kinase (IKK) and the expression of IKKalpha and IKKbeta, the enzymes that phosphorylate IkappaBalpha, in MNCs. Glucose intake caused an increase in NF-kappaB binding to NF-kappaB2, NF-kappaB2a, and NF-kappaB3 sequences in the promoter site of tumor necrosis factor alpha (TNF-alpha) gene along with an increase in the expression of TNF-alpha messenger RNA in MNCs. Membranous p47(phox) subunit, an index of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and activation, also increased after glucose intake. We conclude that glucose intake induces an immediate increase in intranuclear NF-kappaB binding, a fall in IkappaBalpha, an increase in IKKalpha, IKKbeta, IKK activity, and messenger RNA expression of TNF-alpha in MNCs in healthy subjects. These data are consistent with profound acute pro-inflammatory changes in MNCs after glucose intake.     

Implementing a rural programme of prevention of mother-to-child transmission of HIV in Zimbabwe: first 18 months of experience

OBJECTIVE: To report on activities and lessons learned during the first 18 months of a rural programme of prevention of mother-to-child transmission of HIV (PMTCT) in Zimbabwe. METHODS: The PMTCT services were introduced in Murambinda Mission Hospital (120 beds), Buhera, in 2001. Programme strategies consisted in recruiting counselling staff, training health professionals, improving mother-child health (MCH) facilities and conducting information, education and communication activities within the community to address HIV/AIDS awareness and stigma. The following components were implemented within MCH services: voluntary counselling and testing of HIV using rapid testing, nevirapine short regimen proposed to all HIV-infected mothers identified and their newborns, support to exclusive breastfeeding for 6- and 18-month mother-child follow-up. Routine monitoring data collected from August 2001 to February 2003 were used to estimate programme uptake. RESULTS: Of 2471 pregnant women using antenatal services, 2298 were pre-test counselled, the acceptance of HIV testing reached 92.9%. Of the women who decided to take an HIV test, 1588 (74.3%) returned to collect their result. Overall HIV prevalence was 20.4% (n = 437); 326 of the HIV-positive women were counselled and 104 (24%) received complete mother-child antiretroviral prophylaxis. CONCLUSIONS: Acceptability of HIV testing after counselling has remained above 90% since the onset of the programme. Collection of test results and mother-child follow-up are among the most challenging activities of the programme. A district approach and community participation are critical to develop PMTCT programmes in rural settings, even with reasonably good MCH services.     

Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA)

OBJECTIVE: To compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment. DESIGN: Prospective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor. METHODS: A Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4-12 months of treatment or reduction during the first month. RESULTS: Among 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4-12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.1 7-4.29]. Intermediate responders (2.7 < or = RNA < or = 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64-3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31-0.85) and was associated with the viral response during the subsequent 4-12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4-12 month period (P < 0.01). CONCLUSIONS: A sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.     

Impaired fertility in HIV-1-infected pregnant women: a clinic-based survey in Abidjan, Côte d'Ivoire, 1997

OBJECTIVE: Differences in fertility among HIV-1-positive and HIV-negative women tested in prenatal clinics were suspected by routine data collection in Abidjan, C?te d'Ivoire. This study was conducted on detailed fertility patterns among women at the same antenatal care centres, in order to assess these differences. METHOD: The survey was carried out on 1201 consecutive women who agreed to be tested for HIV. Data collected included a detailed account of pregnancies, the time interval between the last two pregnancies, and the health status at the time of the survey. Blood samples were tested for HIV and syphilis with informed consent. RESULTS: Despite an earlier exposure to pregnancy risk, HIV-1-infected women aged 25 years and above, had, on the average, fewer pregnancies than uninfected women. An analysis of the interval between the last two pregnancies among multigravidae showed that, all things being equal, being HIV-1 positive decreased the risk of being pregnant by 17% (Cox regression, hazard ratio = 0.83, 95% confidence interval (CI): 0.69-0.99). This shift in the occurrence of the last pregnancy was more profound among HIV-1-positive women already at the symptomatic or AIDS stage, than among asymptomatic women. CONCLUSION: These data confirm that women infected by HIV-1 would become pregnant less often than uninfected women, for an equal exposure to the risk of pregnancy. Therefore HIV-1-positive women could be under-represented at antenatal centres. Programmes involving such settings both for epidemiological surveillance and the reduction of mother-to-child transmission should take this observation into account.     

Dietary fat modifies mitochondrial and plasma membrane apoptotic signaling in skeletal muscle of calorie-restricted mice

Calorie restriction decreases skeletal muscle apoptosis, and this phenomenon has been mechanistically linked to its protective action against sarcopenia of aging. Alterations in lipid composition of membranes have been related with the beneficial effects of calorie restriction. However, no study has been designed to date to elucidate if different dietary fat sources with calorie restriction modify apoptotic signaling in skeletal muscle. We show that a 6-month calorie restriction decreased the activity of the plasma membrane neutral sphingomyelinase, although caspase-8/10 activity was not altered, in young adult mice. Lipid hydroperoxides, Bax levels, and cytochrome c and AIF release/accumulation into the cytosol were also decreased, although caspase-9 activity was unchanged. No alterations in caspase-3 and apoptotic index (DNA fragmentation) were observed, but calorie restriction improved structural features of gastrocnemius fibers by increasing cross-sectional area and decreasing circularity of fibers in cross sections. Changing dietary fat with calorie restriction produced substantial alterations of apoptotic signaling. Fish oil augmented the protective effect of calorie restriction decreasing plasma membrane neutral sphingomyelinase, Bax levels, caspase-8/10, and −9 activities, while increasing levels of the antioxidant coenzyme Q at the plasma membrane, and potentiating the increase of cross-sectional area and the decrease of fiber circularity in cross sections. Many of these changes were not found when we used lard. Our data support that dietary fish oil with calorie restriction produces a cellular anti-apoptotic environment in skeletal muscle with a downregulation of components involved in the initial stages of apoptosis engagement, both at the plasma membrane and the mitochondria.     

Cervical dysplasia and HIV type 1 infection in African pregnant women: a cross sectional study, Kigali, Rwanda. The Pregnancy and HIV Study Group (EGE)

OBJECTIVE: To study the prevalence of cervical squamous intraepithelial lesions (SILs) and their association with HIV-1 infection and immunodeficiency among pregnant women in Kigali, Rwanda. METHODS: As part of a cohort study on the impact of HIV-1 infection on pregnancy outcome, HIV-1 seropositive (HIV+) and seronegative (HIV-) pregnant women were enrolled during the last trimester of pregnancy at the maternity ward of the Centre Hospitalier de Kigali from July 1992 to August 1993. At inclusion, women were screened for sexually transmitted diseases (STDs)--syphilis, Neisseria gonorrhoeae, chlamydia trachomatis, Trichomonas vaginalis. CD4+ lymphocyte counts were measured and a Papanicolaou smear performed. RESULTS: Papanicolaou smear was interpretable in 103 HIV+ women and 107 HIV- women. Prevalence of SILs was significantly higher in HIV+ women than in HIV- women: 24.3% v 6.5% (odds ratio = 4.6; 95% CI: 1.8-12.3). SIL+ women (n = 32) tended to have more STDs than SIL- women (n = 178), but this did not reach a statistical difference: 37.5% and 24.7% respectively (p = 0.13). They also had a mean CD4 count significantly lower than SIL- women (623 and 784 CD4+ cells x 10(6)/l, respectively; p = 0.02). CONCLUSION: SILs were HIV related and the association with immunosuppression was statistically significant. Prevalence of SILs was high in this population of pregnant women with high HIV/STDs prevalence. Screening policy for STDs and SILs in African women should be assessed in prenatal care.