Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults.

BACKGROUND: Antibody responses to standard regimens of hepatitis B (HBV) vaccination are lower in HIV-infected subjects and the best hepatitis B vaccine schedule in this population is not known. OBJECTIVE: To assess the immunogenicity and to evaluate predictors of serologic response of a modified regimen of a HBV recombinant vaccine in a cohort of HIV-infected subjects. METHODS: HIV-infected subjects received 4 doses (40 µg) of a recombinant HBV vaccine at 0, 1, 2 and 6 months. Demographic information as well as CD4 cell count and plasma viral load were assessed at baseline. Protective and strong responses were defined as an anti-HBs titer ≥10 mIU/mL and ≥100 mIU/mL, respectively and were evaluated one month after the third and the fourth doses. RESULTS: 163 HIV-infected individuals were evaluated 67 (40%) were male and median age was 37 years. Median CD4 cell count was 385 cells/mm(3) and 113 (70%) had undetectable HIV-1 viral load. Protective antibody response was observed in 83 and 91% and a strong antibody response was observed in 62 and 80% of the subjects after 3 and 4 doses, respectively. In a multivariate logistic model undetectable HIV-1 viral load and higher CD4 cell counts were independent predictors of a strong antibody response after 4 doses. Patients with undetectable HIV viral load were almost 3 times more likely to have anti-HBs titers above 100 mIU/mL than those with detectable viral load. CONCLUSIONS: A 4-double-dose regimen of a recombinant HBV vaccine increased response rates and determined higher antibody titers which may translate in prolonged protection against HBV. Inclusion of a fourth dose of HBV vaccine for HIV-infected subjects should be considered in the public health setting.

Community-randomized trial of enhanced DOTS for tuberculosis control in Rio de Janeiro, Brazil.

SETTING: Central Rio de Janeiro, Brazil. OBJECTIVE: To compare the impact of routine DOTS vs. enhanced DOTS (DOTS-Ampliado or DOTS-A) on tuberculosis (TB) incidence. DESIGN: Cluster-randomized trial in eight urban neighborhoods pair-matched by TB incidence and randomly assigned to receive either the DOTS-A or DOTS strategy. DOTS-A added intensive screening of household contacts of active TB cases and provision of treatment to secondary cases and preventive therapy to contacts with latent TB infection (LTBI) to the standard DOTS strategy. The primary endpoint was the TB incidence rates in communities after 5 years of intervention. RESULTS: From November 2000 to December 2004, respectively 339 and 311 pulmonary TB cases were enrolled and 1003 and 960 household were identified in DOTS and DOTS-A communities. Among contacts from DOTS-A communities, 26 (4%) had active TB diagnosed and treated, 429 (61.3%) had LTBI detected and 258 (60.1%) started preventive therapy. TB incidence increased by 5% in DOTS communities and decreased by 10% in DOTS-A communities, for a difference of 15% after 5 years (P = 0.04). CONCLUSION: DOTS-A was associated with a modest reduction in TB incidence and may be an important strategy for reducing the burden of TB.

High rates of serological response to a modified hepatitis B vaccination schedule in HIV-infected adults subjects.

We evaluated a modified HBV regimen in a cohort of HIV-infected subjects in Rio de Janeiro, Brazil. HIV-infected subjects with no serologic evidences of previous hepatitis B infection were immunized with 4 doses (40 microg each) of recombinant hepatitis B vaccine given at 0, 1, 2 and 6 months. Blood samples were collected 1 month after the last dose and anti-HBs titers were measured. A protective antibody response was defined as an anti-HBs titer >or=10 mIU/mL. Forty-seven subjects (30 women, 17 men; mean age was 36 years, ranging from 21 to 58 years) were included in the final analysis. Median baseline CD4+ lymphocyte count was 402 cells/mm(3) and 33 subjects (70%) had an HIV viral load below 80 copies/mL. A protective antibody response was observed in 42 (89%) subjects. Thirty-seven (78%) and 28 (60%) patients developed anti-HBs titers higher than 100 mIU/mL and 1000 mIU/mL, respectively. 1 out of 5 non-responders (20%) had an HIV viral load below the detection limit, in contrast with 32 (76%) of those with an adequate serologic response (p=0.02). These findings suggest that 4-double dose alternative schedule may be considered to overcome the lower seroconversion rates observed with the standard regimens in HIV-infected subjects.

CYP3A5 genotype has no impact on plasma trough concentrations of lopinavir and ritonavir in HIV-infected subjects.

CYP3A5 genotype has no impact on the trough plasma concentrations of lopinavir and ritonavir in human immunodeficiency virus (HIV)-infected individuals on stable highly active antiretroviral therapy (HAART). This is ascribed to a drug interaction, such that ritonavir by inhibiting CYP3A activity, may occlude the pharmacokinetic consequences of functional polymorphisms in the CYP3A5 gene. In the clinical setting, where lopinavir and ritonavir are always combined, CYP3A5 genotype is of no consequence on the trough plasma concentrations of these drugs.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil.

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73%), 55 (11%), and 76 (16%) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25%) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73 percent), 55 (11 percent), and 76 (16 percent) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25 percent) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

Occupational exposures to bloodborne pathogens among healthcare workers in Rio de Janeiro, Brazil.

Healthcare workers (HCWs) frequently face the risk of occupational infection from bloodborne pathogens following exposure to blood and body fluids. This study describes the results of a surveillance system of occupational exposure to bloodborne pathogens among HCWs in Rio de Janeiro, Brazil, during an eight-year period. A total of 15 035 exposures reported from 537 health units were reviewed. Six circumstances comprised nearly 70% of the reported exposures: recapping needles (14%), performing surgical procedures or handling surgical equipment (14%), handling trash (13%), during disposal into sharps containers (13%), performing percutaneous venepuncture (10%) and during blood drawing (5%). Easily preventable exposures, such as incidents related to recapping needles, handling trash, and sharps left in an inappropriate place, represented 30% of the exposures reported. Post-exposure prophylaxis (PEP) for human immunodeficiency virus (HIV) was initiated for 46% of exposed HCWs. Although Brazilian guidelines indicate that PEP is usually not recommended for exposures with insignificant or very low risk of HIV infection, PEP was prescribed to a large proportion of exposed HCWs under these circumstances. The prevention of occupational exposure to bloodborne pathogens among HCWs and their safety must be considered as a public health issue. Although infection-preventative measures such as antiretroviral drugs and rapid tests are available, this study shows that there are still a high number of easily preventable exposures. The implementation of more effective prevention strategies is urgently required in this country.

Effect of antiretroviral therapy on HIV shedding in semen.

BACKGROUND: The effect of antiretroviral therapy on seminal HIV shedding in the community remains unknown. OBJECTIVE: To evaluate the effect of antiretroviral therapy on HIV shedding in semen. DESIGN: Prospective cohort study. SETTING: University hospital in Rio de Janeiro, Brazil. PATIENTS: 93 HIV-infected men. INTERVENTION: Antiretroviral therapy as prescribed by each patient's physician. MEASUREMENT: HIV RNA in semen and blood plasma before and after introduction of therapy. RESULTS: At baseline, HIV RNA was detected in 69 semen samples (74%) and 89 blood samples (96%). Six months after introduction of therapy, HIV RNA was detected in 29 semen samples (33%) and 33 blood samples (38%). The mean reduction in levels of HIV RNA in semen at 6 months was 1.65 log10 units. CONCLUSIONS: Antiretroviral therapy reduces shedding of HIV in semen, which probably in tum reduces HIV transmissibility. However, a substantial proportion of patients may still be infectious and may have drug-resistant strains of the virus.

Role of different methods for the detection of diarrhoeal pathogens in HIV-infected patients in Brazil.

To evaluate the ability of different diagnostic methods for the detection of AIDS-related diarrhoeal pathogens in developing countries, we studied 40 HIV-infected patients with diarrhoea. All patients were subjected to stool examinations for parasites, stool culture and peroral jejunal biopsy. Jejunal specimens were processed for histological examination with several stains and for transmission electron microscopy (TEM). Jejunal juice and mucosa were cultured. An aetiologic agent was found in twenty patients. Eleven stool specimens were positive for parasites and stool culture was positive in three patients. The enteropathogens detected by these two methods included every microorganism amenable to treatment. Histological examination revealed four agents not previously identified. TEM added to diagnosis in only two patients. All cultures of jejunal mucosa and jejunal juice were negative, even when stool culture was positive. We conclude that a minimal investigation consisting of stool examination for parasites and stool culture is a cost-effective strategy in the management of AIDS-related diarrhoea in developing countries.

PIP: The authors report findings from their evaluation of the ability of different diagnostic methods to detect AIDS-related diarrheal pathogens in developing countries. 40 HIV-infected patients with diarrhea participated in the study, having their stools examined for parasites and submitting to stool culture and peroral jejunal biopsy. Jejunal specimens were processed for histological examination with several stains and for transmission electron microscopy (TEM). Jejunal juice and mucosa were cultured. An etiologic agent was found in 20 patients, with 11 stool specimens positive for parasites and stool culture positive in three patients. The enteropathogens detected by these two methods included every microorganism amenable to treatment. Histological examination revealed four agents not previously identified. TEM added to diagnosis in only two patients. All cultures of jejunal mucosa and jejunal juice were negative, even when stool culture was positive. The authors conclude that a minimal investigation consisting of stool examination for parasites and stool culture is a cost-effective strategy in the management of AIDS-related diarrhea in developing countries.

Jejunal biopsy in HIV-infected patients.

Forty-nine HIV-infected patients were submitted to peroral jejunal biopsy in order to evaluate the presence of microorganisms and the histomorphometric aspects of the enteric mucosa with subsequent correlation of these findings to the appropriate clinical stage of the disease. Thirty-seven patients fulfilled the CDC criteria for AIDS, of whom 23 presented with diarrhea. Of the 12 patients who had not yet been given an AIDS diagnosis. 3 had persistent generalized lymphadenopathy and 9 were asymptomatic carriers. Flat mucosa was observed in two patients (8.7%) with diarrhea and coccidea. Subtotal villous atrophy and severe lamina propria (LP) mononuclear infiltrate (13%) were found only in patients with diarrhea. Moderate to severe histologic changes were more frequently observed in this group, not always related to the presence of microorganisms. Crypt hyperregeneration was a constant finding. Intraepithelial lymphocyte (IEL) count was decreased in patients with diarrhea. Specific infectious agents were unexpectedly rare for the tropical developing country population studied. The organism most commonly associated with diarrhea was Cryptosporidium sp. (21.7%). The etiology of diarrhea in a significant number of patients remains unclear.