Causes of death and risk factors among HIV-infected persons in the HAART era: analysis of a large urban cohort.

OBJECTIVE: We aimed to examine the clinical outcome in HIV-1-infected patients after more than 10 years of highly active antiretroviral therapy (HAART). METHODS: We analyzed data from 1,236 treatment-naïve adults who had started HAART. The primary endpoint was the yearly prevalence of death for AIDS-related causes (ARC) or for non-AIDS related causes (non-ARC). The data from our cohort were compared with that of the general population (GP) of our region. RESULTS: We observed that 116 patients died, and 58.6% of deaths were non-ARC. The death incidence decreased from 18.8% in 1998-1999 to 1.2% in 2008-2009. The leading causes of death were malignancies (35.3%), infections (21.6%), end-stage liver diseases (18.1%), and cardiovascular diseases (CVD) (6.9%). Yearly death rates were similar in the HIV-infected cohort and in the crude GP (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.5-2.5), but when adjusted for age, HIV-infected patients showed a greater risk (OR 7.4, 95% CI 4.1-13.4). The difference was still highly significant when the analysis was restricted to non-ARCs (OR 4.3, 95% CI 2.07-9.2). Overall, malignancies (OR 5.7, 95% CI 2.6-12.8) and end-stage liver diseases (OR 35.0, 95% CI 15.5-78.8) were significantly more frequent than in the age-adjusted GP. CONCLUSIONS: Despite HAART, HIV-infected patients are at greater risk of death compared to a reference uninfected population.

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4.

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

Severe lactic acidosis and thiamine administration in an HIV-infected patient on HAART.

Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV treatment. We report on an asymptomatic HIV-infected woman treated with stavudine, lamivudine and indinavir for one year. She was hospitalized because of progressive dispnoea, oedema, cyanosis and severe lactic acidosis. Arterial blood pH was 6.98, bicarbonate 4.4 mmol/l (normal value 22-26), blood lactate: 29.7 mmol/l (normal value <2.2). Hepatic function was normal. She had an impressively rapid response (within a few hours) to empirical treatment with thiamine (100 mg i.v.). No evidence of sepsis or malabsorption were identified and vitamin B1 level was not tested before thiamine infusion. Three months later she was re-started successfully on nelfinavir plus nevirapine. The rapid response to thiamine infusion deserves a careful attention and such an approach should be considered in similar cases as a support treatment of this potentially life-threatening complication of HIV therapy.

Four drug-HAART in primary HIV-1 infection: clinical benefits and virologic parameters.

BACKGROUND: From a theoretical standpoint, primary HIV infection (PHI) represents a great chance to modify the natural history of the disease. In this study we purposed a four drugs regimen with zidovudine, lamivudine, ritonavir and saquinavir to treat aggressively the infection and achieve a complete immune reconstitution. METHODS: This is an Italian multicentric open label study. Adult patients with PHI were eligible for the study if they met at least one clinical criterion and one laboratory criterion of the following. Clinical criteria: Signs and symptoms of acute retroviral syndrome within the past 70 days, exposure to HIV-1 within the last 3 months, a preceding negative antibody test within the past 6 months. Laboratory criteria: Detectable p24 antigen with neutralization in serum; detectable HIV-RNA in plasma; indeterminate Western blot test with negative or low positive value HIV antibody in ELISA test. RESULTS: Since April 1997 to April 1999 40 patients with PHI have been enrolled; 80% of this cohort referred symptoms related to acute antiretroviral syndrome. Treatment has been withdrawn in 17 patients (12 for intolerance, 3 for toxicity and 2 for failure). At baseline the mean CD4+ T cells count and CD4/CD8 ratio were 537 (range 55-1287) and 0.58 (range 0.1-1.03) and the mean plasma HIV-RNA level was 5.9 log copies/ml (range 3-7.15). Plasmatic HIV-1 RNA levels of all patients dropped below 200 copies/ml in 68% of patients at week 12, 81% at week 24, 93% after 12 months and 100% after 18 months. Immunological parameters have been improved and have achieved normal range since 6th month. CONCLUSIONS: A rapid virologic suppression and immunological reconstitution are associated with PHI therapy. However early treatment should be weighted against the potential disadvantages such as immediate adverse events (intolerance and drug toxicity) and long term manifestation (metabolic disorders).

[Evolution of hepatitis G in children with vertically transmitted HGV] / Evoluzione dell'infezione da HGV (GBV-C) trasmessa per via verticale.

Background A new hepatitis-associated RNA virus, belonging to the Flaviviridae, has been recently discovered and called HGV (GBV-C). This virus has been shown to be transmitted parenterally. In this study we examined a group of children born to HCV infected women. Methods Between September 1994 and December 1998, we studied a cohort of 53 pregnant women, aged between 20 and 43 years. They were all HCV Ab and HCV RNA positive, with a diagnosis of chronic hepatitis. One patient was HbsAg positive and 4 patients (pts.) (7.5%) were HIV Ab positive. Anamnestic information revealed that: 28 pts. (52.8%) were IVDUs, 11 pts. (20.8%) had been haemotransfused and 14 pts. (26.4%) had no risk factors. We examined HGV RNA by RT nested PCR, using primers from the 5'UTR of HGV. Anti-HGV antibodies (anti-E2) were detected with an ELISA test using recombinant E2 protein. Ten of the 53 pregnant women (18.9%) were HGV RNA positive (32 other pts., 60.4%, were positive for anti-E2 antibodies). We monitored their children for 18-24 months (with clinicai and haematological controls), looking for HGV RNA, anti-E2 antibodies, HCV RNA and for ALT serum levels. Results Seven (70%) new-bom children proved HGV RNA positive at follow-up; all babies were HCV RNA negative at controls. Four of them were born vaginally; none of them was breast-fed. HGV RNA was first detectable at the 3rd month of life in 3 babies, and all babies were HGV RNA positive at the 6th month of life. Six babies (85.7%) remained positive during the observation period. One baby (14.3%) seroconverted at 10 months, developing anti E-2 antibodies and becoming HGV RNA negative. Four babies (57.1%) maintained normal ALT serum levels during the whole follow-up period, while 3 patients showed a low increase in ALT serum levels. The ALT values normalised at later controls. Conclusions HGV infection shows a very high (70%) rate of vertical transmission but a low and doubtful pathogenicity with asymptomatic evolution in babies. Patients who did not develop anti-E2 antibodies at the 12th month of life remained infected without persistent signs of hepatic failure.

[Evolution of hepatitis C virus (HCV) infection acquired at birth] / Andamento dell'infezione da virus dell'epatite C (HCV) acquisita alla nascita.

Objectives Our aim was to analyze the evolution of HCV infection in children infected at birth. Methods Between September 1994 and December 1998 we analyzed in a prospective study 8 children born of anti-HCV and HCV RNA positive women. Each baby was controlled at birth, every 3 months during the first year of life, and then every 6 months searching for anti-HCV antibodies (ELISA 3, RIBA 2-3), HCV RNA (RT PCR), ALT and viral genotype. Results Viral RNA was detectable in the first 3 months of life in all babies (100%) and remained positive during the follow-up. Viral genotypes were the same for mothers and their children. In 6 babies (75%) ALT remained pathologic during follow-up. Conclusions HCV infection in children usually has an asymptomatic outcome; the infection has chronic features in the majority of cases.