The retrovirus LP-BM5 murine leukemia virus induces murine AIDS in C57BL/6 mice that has many similarities with human AIDS; Plasmodium berghei ANKA causes experimental cerebral malaria in the same strain of mice. The outcome of malaria infection was studied in mice concurrently infected with the two pathogens. The retrovirus significantly reduced the gravity of the neurological manifestations associated with Plasmodium berghei ANKA infection. The protection against experimental cerebral malaria induced by murine AIDS increased with duration of viral infection and, hence, with the severity of the immunodeficiency. Interleukin 10, principally from splenic T cells, was shown to play a crucial role in this protection.

HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in Brazil. Differences in prognosis for patients infected with serotype B-Br or serotype B (GPGR) have not been addressed previously. In this prospective cohort study, we compared the rate of disease progression between patients infected with the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV-infected patients who were tested with a specific enzyme immune assay, 204 (46%) had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load, initial clinical stage, and the proportions who were treated with antiretroviral drugs. Patients with serotype B infection were significantly younger (p = 0.005) and tended to report homosexual behavior more frequently (p = 0.08). Mean follow-up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p = 0.03). In a regression model adjusted for age and risk factor for HIV infection, progression to AIDS was faster in patients infected with serotype B (hazard ratio [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p = 0.09). These results suggest that patients infected with closely related HIV-1 serotypes may differ in the rate of progression to AIDS and indicate that serotype should be taken into account in HIV vaccine studies in Brazil.

African green monkeys (AGMs) are divided into four species (Cercopithecus aethiops, C. pygerythrus, C. sabaeus, C. tantalus), each harboring a species-specific simian immunodeficiency virus (SIVagm). Little is known about the host and/or viral factors that are responsible for the apathogenicity of SIVagm infections in their natural hosts. In order to analyze the specific selective pressures exerted by the host on the virus in vivo, we compared the genetic evolution of SIVagm.tan in its natural host (C. tantalus) and in a foreign host species (Erythrocebus patas), in which we could obtain a reproducible and persistent infection by SIVagm.tan. As in AGMs, patas monkeys do not develop any disease following SIVagm infection. Our longitudinal study in env (V3-C3-V4-C4-V5) of SIVagm.tan from three AGMs and three patas monkeys revealed a high ratio of synonymous to nonsynonymous mutation frequencies (1.5-6.2). These data indicate that the selective pressures for stability exerted by AGMs and patas monkeys on SIVagm override positive selection for change reported in pathogenic HIV-1 infections. The rapid accumulation of mutations observed in AGMs and patas monkeys (0.4-7.2 x 10(-2) nucleotide substitutions per site per year) suggests a continuous replication of SIVagm viruses in vivo. We thus propose that nonpathogenic SIVagm infections are the result of a long-term selection of SIVagm variants whose dissemination can be controlled in the host, rather than being explained by a low ability of the virus to replicate in vivo.

The presence of genetic mutations in HIV-1-positive untreated individuals and its contribution to treatment failure, either in an individual or on a population basis, remains an important concern. The goal was to analyze and compare HIV-1 reverse transcriptase (RT) and protease (PR) genes of untreated individuals with chronic and recent infections. Fifty-one chronic infected individuals for whom initiation of antiretroviral treatment had been recommended and 20 individuals with recent documented HIV-1 seroconversion had their plasma viral RNA extracted and the PR and RT genes sequenced in order to determine subtype, presence of genetic polymorphisms and mutations associated with resistance to antiretroviral drugs. All 20 recent seroconvertors were infected with subtype B viruses. Of the 51 chronically infected patients, 40 (78.4%), 7 (13.7%), and 2 (3.9%) were infected with subtypes B, F, and C, respectively. Two (3.9%) hybrid forms were also observed in two individuals with chronic infection: D/B and D/F. Despite seroconversion stage, type and quantity of mutations were similar to both groups (P = 0.961). This group also presented the only (1.4%) drug-resistance mutation (M184V) among all samples investigated. In summary, the present study shows a high occurrence of equivalent polymorphisms unrelated to drug resistance in samples collected from untreated HIV-1- infected individuals in different seroconversion status, and suggests low primary resistance mutations. Results also indicate that non-B subtypes circulating in Rio de Janeiro have specific Brazilian non-synonymous mutations.