Jorge Casseb

Impact of Adherence to Antiretroviral Therapy in HIV-1–Infected Patients at a University Public Service in Brazil

The objective of this study was to assess if a simple evaluation, adherence to antiretroviral therapy, would correlate to clinical and laboratory outcomes. We followed an open cohort of patients from a public teaching hospital AIDS outpatient clinic. Patients were categorized according to adherence as: regular (Reg), optimal, all doses all days, tolerating only irregular timing (+/- 2 hours) of intake; quasi-regular (qReg), those missing up to four doses or 1 full day during a month; irregular (Irreg), all other irregular regimens, and ignored (Ign), those without information. The results from a simple questionnaire were compared to CD4+ cell counts and human immunodeficiency virus type 1 (HIV-1) RNA plasma viremia. One hundred eighty-two HIV-1-infected patients (126 males, 69%; 56 females, 31%) were analyzed. Information on adherence was available for 168 (90%). Reg adherence was reported by 75 (41%) patients, qReg adherence by 35 (19%), and Irreg by 53 (29%) of patients. The main reasons for nonadherence were forgetfulness, intolerance, use of alcohol, and misunderstanding of prescription. A significant increase of CD4+ T-cell counts and absolute gain were only observed among Reg and qReg users (p < 0.001). The median viral RNA load log10 decreases were -1.68, -1.45, -0.9 log, respectively, for Reg, qReg, and Irreg patients (p = 0.043, Kruskal-Wallis). Development of and death from AIDS occurred almost exclusively among those with Ign or Irreg adherence. Previous use of antiretroviral therapy may have had an impact in treatment response. Individuals who were treatment-naive were more likely to be Reg users (41%). Although more refined methods to assess adherence should be implemented when available, the inability to do so should not prevent simple, albeit subjective measurements that also correlate with favorable outcome. Mechanisms to improve adherence should be considered an integral part of antiretroviral therapy.

Use of doxycycline for leptospirosis after high-risk exposure in São Paulo, Brazil

A clinical trial pilot study, double-blinded, randomized, and controlled with a placebo to assess the effectiveness of oral doxycycline (200 mg, single dose) in preventing leptospirosis after high exposure to potentially contaminated water was performed in São Paulo, SP, Brazil. Confirmed cases were defined as those with leptospira IgM antibody and symptoms; asymptomatic cases were those presenting with IgM antibodies but no symptoms; and suspected cases were individuals with symptoms but no IgM antibody. Forty subjects were given doxycycline and 42 were given placebo. In the drug-treated group there were 2 confirmed cases, 11 asymptomatic cases, and 6 suspected cases. In the placebo group there were 5 confirmed, 6 symptomatic, and 5 suspected cases. Even though we found a protective association of doxycycline for confirmed leptospirosis cases (RR = 2.3) and seroconversion only (RR = 2.0), the association was not statistically significant because of the small number of individuals enrolled in this pilot study. We observed that the 22% of the volunteers already had IgM antibodies to leptospirosis at the first sampling. Finally, the attack rate to confirmed, asymptomatic, and suspected cases of Leptospirosis was 8.5%, 22%, and 13%, respectively, in this population.

Corticosteroid therapy in TSP/HAM patients: the results from a 10 years open cohort.

BACKGROUND The use of corticosteroids for treating tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) has yielded controversial results. We report the use of corticosteroids for the treatment of TSP/HAM in an open cohort. METHODS The clinical efficacy of long-term, high dose of corticosteroid therapy was studied in thirty-nine TSP/HAM patients. Disability and motor dysfunction was evaluated based on the Disability Status Scale (DSS), Osames Motor Disability Scales (OMDS), and Incapacity Status Scale (ISS), before and after treatment. Treatment included use of methyl-prednisolone, 1 g/day for three days, every 3-4 months. The primary end-point was a change in the scores of the neurological scales from baseline until the fifth visit after therapy. RESULTS After a mean follow-up of 2.2 years and an average of four pulses per patient, we noted a significant neurological improvement, reaching 24.5% according to the ISS score. No statistically significant differences in scores according to the OMDS and DSS scales were noted. CONCLUSION We observed neurological improvement with the use of corticosteroids, with physical therapy and antispastic-drugs as adjunctive treatment. However, randomized clinical trials should be done to assess the use of corticosteroids and other potentially useful immune-based therapies for TSP/HAM treatment.

Maternal HIV-1 antibody and vertical transmission in subtype C virus infection.

Summary: The role of maternal humoral immune response and viral load was analyzed in relation to the incidence of mother‐to‐child transmission (MTCT) of infants born to HIV‐1 subtype C infected mothers. High levels of viral RNA in the serum correlated with MTCT as did high titers of subtype C consensus V3 peptide binding antibodies (BA) and neutralizing antibody (NA) to subtype B HIV‐1MN. Logistic regression analysis showed that maternal viral load and V3 peptide subtype C BA were independent predictors for MTCT, odds ratio (OR) = 2.22 and OR = 2.52, respectively. No correlation between NA to homologous HIV‐1 subtype C virus and MTCT was found. BA to V3 peptides may provide a rapid inexpensive method that can be used to determine the risk of HIV‐1 MTCT.

AIDS Incidence and Mortality in a Hospital-Based Cohort of HIV-1–Seropositive Patients Receiving Highly Active Antiretroviral Therapy in São Paulo, Brazil

Brazilian AIDS and HIV-1-seropositive patients have had free access to highly active antiretroviral therapy (HAART) since November 1996. Although secondary data based on official mortality statistics indicate a sharp decrease in AIDS mortality, few if any studies tried to estimate the prognosis for patients with HIV who have been followed from the beginning of the HAART era. An observational study, with retrospective and prospective components, was done in 233 adult HIV-1-infected subjects who were recruited in the last 10 years at the outpatient sector of the Secondary Immunodeficiencies Clinic of the Department of Dermatology, Hospital das Clinicas da FMUSP, Sao Paulo, Brazil. The definition of AIDS followed the guidelines issued by the Centers for Disease Control (CDC) in 1987. One hundred sixty patients were asymptomatic, 46 had AIDS, 24 had AIDS-related complex, and 3 presented with acute infection at study entry. Twenty-nine (18%) of the asymptomatic subjects developed AIDS during follow-up, with 5 (3%) deaths. Among the 46 AIDS cases at entry, 7 (17%) died during follow-up. Thus, a total of 12 people (5.2%) died of AIDS in this cohort over a mean follow-up of 5.2 years and 24 people were lost to follow-up (10.3%). Ninety percent of the survivors were on combined therapy (82% with 3 or more drugs, and 8% with 2 drugs), while 10% were not taking antiretrovirals. People with AIDS at entry were 5 times more likely to die during this period compared to patients who were asymptomatic at entry (p = 0.006). Women showed better outcomes than men, reflecting differences in CD4+ T-cell counts at study entry. All but 1 patient progressed to AIDS during the pre-HAART era (before 1996). In spite of its recent decline, mortality from AIDS-related conditions remains an important public health issue.

Presence of tropical spastic paraparesis/human T‐cell lymphotropic virus type 1‐associated myelopathy (TSP/HAM)‐like among HIV‐1‐infected patients

Human immunodeficiency virus type 1 (HIV‐1) and human T‐cell lymphotropic virus types 1 and 2 (HTLV‐1 and ‐2) are retroviruses that share similar routes of transmission and some individuals may have a dual infection. These co‐infected subjects may be at increased risk for tropical spastic paraparesis/HTLV‐1‐associated myelopathy (TSP/HAM)‐like. To study the prevalence of tropical spastic paraparesis/HTLV‐1‐associated myelopathy (TSP/HAM) among co‐infected HIV‐1/HTLV‐1 subjects. Since July 1997, our group has been following a cohort to study the interaction of HTLV with HIV and/or hepatitis C virus (HCV), as well as HTLV‐1‐only infected asymptomatic carriers or those already presenting with TSP/HAM. During these 9 years, 296 HTLV‐1‐infected individuals were identified from a total of 538 patients who were referred to our clinic at the Institute of Infectious Diseases “Emílio Ribas,” in São Paulo, Brazil. All subjects were evaluated by two neurologists, blinded to the HTLV status. TSP/HAM diagnosis was based on Kagoshima diagnostic criteria. Results: A total of 38 HIV‐1/HTLV‐1 co‐infected subjects were identified in this cohort: Twenty‐six had already been diagnosed with AIDS and 12 remained asymptomatic. Six of 38 co‐infected subjects (18%) were diagnosed as having TSP/HAM and also AIDS, and for 5 of them TSP/HAM was their first illness. One additional incident case was diagnosed after 2 years of follow‐up. No modifications on HIV‐1 viral load was seen. In contrast, the co‐infected with TSP/HAM‐like group showed higher HTLV‐1 proviral load (505 ± 380 vs. 97 ± 149 copies/104 PBMC, P = 0.012) than asymptomatic co‐infected subjects, respectively. The incidence of myelopathy among HIV‐1/HTLV‐1 co‐infected subjects is probably higher than among patients infected only with HTLV‐1, and related to a higher HTLV‐1 proviral load. Thus, HTLV‐1/2 screening should be done for all HIV‐1‐infected patients in areas where HTLV‐1 infection is endemic. J. Med. Virol. 80:392–398, 2008.

Prevalence of human T cell leukemia virus-I (HTLV-I) antibody among populations living in the Amazon region of Brazil (preliminary report)

Forty-three (31.4%) out of 137 serum samples obtained from two Indian communities living in the Amazon region were found to be positive for HTLV-I antibody, as tested by enzyme-linked immunosorbent assay (ELISA). Eighty-two sera were collected from Mekranoiti Indians, yielding 39% of positivity, whereas 11 (20.0%) of the 55 Tiriyo serum samples had antibody to HTLV-I. In addition, positive results occurred in 10 (23.2%) out of 43 sera obtained from patients living in the Belem area, who were suffering from cancer affecting different organs. Five (16.7%) out of 30 ELISA positive specimens were also shown to be positive by either Western blot analysis (WB) or indirect immunogold electron microscopy (IIG-EM).

Origin and Prevalence of Human T-lymphotropic Virus Type 1 (htlv-1) and Type 2 (htlv-2) among Indigenous Populations in the Americas

Human T-lymphotropic virus type 1 (HTLV-1) is found in indigenous peoples of the Pacific Islands and the Americas, whereas type 2 (HTLV-2) is widely distributed among the indigenous peoples of the Americas, where it appears to be more prevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is considered ancestral in the Americas and is transmitted to the general population and injection drug users from the indigenous population. In the Americas, HTLV-1 has more than one origin, being brought by immigrants in the Paleolithic period through the Bering Strait, through slave trade during the colonial period, and through Japanese immigration from the early 20th century, whereas HTLV-2 was only brought by immigrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous people of Brazil makes the Brazilian Amazon the largest endemic area in the world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports the African origin of HTLV-1 in Brazil. The risk of hyperendemicity in these epidemiologically closed populations and transmission to other populations reinforces the importance of public health interventions for HTLV control, including the recognition of the infection among reportable diseases and events.

Two variants of HIV-1 B serotype are transmitted heterosexually in São Paulo, Brazil

HIV-1 variability may have an important impact on transmission and pathogenicity. Better characterization of the HIV epidemic in Brazil is necessary for the development of vaccine trials in this country. We analyzed sera from 108 HIV-1-infected volunteers from São Paulo City to determine serotype and reactivity for V3 motifs of HIV in this population, and the relationship to transmission mode. We concluded that the HIV-1 B serotype is frequent among heterosexually infected women, even in the absence of anal sex, and that two major V3 motifs, GPGR and GWGR, had similar prevalence among women (48% and 52%, respectively) and men (56% and 44%, respectively). We also observed an equal distribution of these strains regardless of their CD4+ T cell counts, clinical status, and mode of transmission. Even though V3 serology for HIV-1 subtyping is an inexpensive tool for use in developing countries, additional methods, such as heteroduplex mobility assay and direct DNA sequencing, should be included to determine HIV-1 genetic diversity.

CD4+ T-Cell Recovery and Clinical Outcome in HIV-1-Infected Patients Exposed to Multiple Antiretroviral Regimens: Partial Control of Viremia Is Associated with Favorable Outcome

The goal of antiretroviral therapy is clinical benefit through the suppression of viral replication and the immunologic reconstitution of HIV-1-infected patients. In spite of the availability of different highly active antiretroviral therapy only some patients sustain undetectable plasma viremia. We performed an observational study from October 1987 to February 2001 on immunologic and clinical outcome of 148 HIV-1-infected patients from an open clinical cohort at São Paulo University, Brazil. The median T CD4+ at starting first monitored regimen was 227 cells per microliter, with 65% of patients previously exposed to antiretroviral regimens, mostly dual therapy. Virologic response to antiretroviral therapy, after a median period of 179 weeks of monitored treatment, allowed classifying patients as aviremic (RNA plasma viremia below 500 copies per milliliter); viremic (current viral load at historic levels), and viremic-attenuated groups (detectable viremia, but > 1 log viral suppression). HIV RNA viral load, T CD4+ cells count, HIV-1 pol sequencing, inflammatory parameters, and clinical events were documented during a median follow-up of 251 weeks. This study observed better clinical and immunologic responses in the aviremic group, but the viremic-attenuated group showed a significant gain in CD4+ cells (p < 0.013) and a decreased number of cases progressing to an AIDS-defining clinical condition (p < 0.001) compared to the viremic group.