HIV drug resistance and implications for the introduction of antiretroviral therapy in resource-poor countries.

The development and transmission of HIV drug-resistant viruses is of serious concern and has been shown to significantly diminish the effectiveness of antiretroviral therapy. In addition, cross-resistance between drugs of the same class can seriously limit therapeutic options and may potentially be most problematic in resource-poor settings where new drugs are not widely available. Strategies based on avoidance of virological failure are therefore essential for the long-term success of therapy. In this regard, regionally adapted programs to facilitate proper adherence with therapy need to be urgently implemented, concomitant with expanded access to new antiretroviral drugs. The value of genotypic resistance testing as a prognostic tool to help guide therapeutic decisions has been established. However, the relatively high cost of this novel technology does not warrant its routine utilization at this time in resource-poor countries. Lastly, the genetic barrier of the antiretroviral agents that are prescribed is also an important consideration that needs to be integrated with knowledge of HIV-1 subtypes, drug pharmacology, and medical management of concurrent illnesses. The selection of appropriate first-line antiretroviral combination regimens may be an even more important consideration in developing than developed countries, given that options in the aftermath of treatment failure may be more limited in such settings.

Inhibition of human immunodeficiency virus type-1 (HIV-1) replication by immunor (IM28), a new analog of dehydroepiandrosterone.

The inhibition of HIV-1 replication in vitro by Immunor 28 (IM28), an analog of dehydroepiandrosterone (DHEA), was monitored using the HIV-1 laboratory wild-type strain IIIB. Evaluation of the 50% inhibitory dose (IC50) revealed a decrease in HIV-1 replication giving an IC50 value around 22 microM. The toxicity of the drug has been determined also, in MT2 cells and PBMCs. 60 microM of IM28 provoked a 50% decrease in cell viability while DHEA caused the same decrease at 75 microM in MT2 cells. These values are 125 microM for IM28 in PBMCs and 135 microM for DHEA. Thus, DHEA is less toxic than IM28, but IM28 has a higher antiviral activity.

[Intrathecal synthesis of anti-Toxoplasma gondii antibodies during cerebral toxoplasmosis associated with African AIDS]. / Synthèse intrathécale d'anticorps anti-Toxoplasma gondii au cours de la toxoplasmose cérébrale associée au sida africain.

Thirty-four HIV-1-infected in-patients of the Hôpital Central des Forces Armées Congolaises, Brazzaville, Congo, hospitalized for suspected cerebral toxoplasmosis, have been evaluated for integrity of the blood-brain barrier, intrathecal synthesis of total IgG, toxoplasmic serology in blood and cerebrospinal fluid, and for intrathecal synthesis of IgG to Toxoplasma gondii. An empiric scale to gauge the possibility of clinical cerebral toxoplasmosis was used to classify the patients (+, +2, +3). Only an intrathecal synthesis of IgG to Toxoplasma gondii was found to be associated with suspected cerebral toxoplamosis: it was found in about 80% of patients, and more frequently in patients with a higher probability of disease. In contrast, alteration of the blood-brain barrier, intrathecal synthesis of total IgG and toxoplasmic serology in blood as well as in cerebrospinal fluid were not associated with suspected cerebral toxoplamosis. Taken together, these findings confirm that intrathecal synthesis of antitoxoplasmic antibodies of IgG isotype occurs in cerebral toxoplasmosis. Demonstration of intrathecal synthesis of antitoxoplasmic IgG antibodies could be used to confirm clinical diagnosis of cerebral toxoplamosis, especially in an African context, where sophisticated laboratory facilities are often lacking.

Antibody production and blastogenic response in pigs experimentally infected with porcine reproductive and respiratory syndrome virus.

Seven five-week piglets were infected intranasally with 10(5) TCID50 of porcine reproductive and respiratory syndrome (PRRS) virus strain IAF.exp91. All virus-exposed pigs developed fever, labored abdominal breathing, conjunctivitis, and lymph node enlargement within the first 96 h postexposure (PE), which continued to d 10 to 14 PE. Two pigs that were necropsied at d 7 and 10 PE had diffuse interstitial pneumonitis, cardiopathy and lymphadenopathy. All 5 remaining pigs produced serum IgM and IgG antibodies against PRRS virus by 7 or 14 days PE, as demonstrated by indirect immunofluorescence. This corresponded with the capability of isolating the virus from serum d 7 to d 49 or d 63 PE. Low serum neutralizing antibody titers were detected in 3 of the virus-exposed pigs by 35 days PE. A transient episode of diminished proliferative response of peripheral blood lymphocytes to mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) was observed in the virus-exposed pigs at d 3 PE. However, in vitro spontaneous uptake of [3H]-thymidine was significantly increased in lymphocyte cultures of the same pigs at d 7 or d 14 PE. These results suggest polyclonal activation of peripheral blood lymphocytes.

Kinetics of humoral immune response to the major structural proteins of the porcine reproductive and respiratory syndrome virus.

The kinetics of appearance of antibodies directed to the major structural proteins N, M and E of porcine reproductive and respiratory syndrome virus (PRRSV) was followed in pigs naturally- and experimentally-exposed to the virus. Specific IgM antibody titers were first detected by indirect immunofluorescence (IIF) at the end of the first week of PRRSV infection, peaked by day 14 to 21 post-inoculation (p.i.), then rapidly decreased to undetectable levels by day 35 to 42 p.i. On the other hand, specific IgG antibody titers peaked by day 21 to 28 p.i. and remained unchanged to the end of the 6- or 9-week observation period; in addition, a persistent viremia was observed. Virus neutralizing (VN) antibody titers > 8 were not detected until 3 to 4 weeks p.i. Taken together, the results obtained by Western blotting analyses using purified virus and E. coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i.

[Impact of AIDS on the resurgence of tuberculosis and reduced availability of hospital beds in Brazzaville (Congo)]. / Impact du SIDA sur la recrudescence de la tuberculose et la réduction de la disponibilité des lits hospitaliers à Brazzaville (Congo)

Our objective was twofold: firstly to evaluate the impact of AIDS on the annual increase of tuberculosis morbidity in Brazzaville; and secondly, to show its consequences on the reduced availability of hospital beds for patients treated for diseases nonrelated to AIDS. This retrospective study included 541 tuberculosis patients who were treated from 1988 to 1992 in the Department of Medicine at the Military Central Hospital in Brazzaville. The serum of all patients was tested by ELISA and Western blots for the presence of HIV. HIV and tuberculosis coinfection were very frequent (more than 30% of all AIDS cases), particularly among young people (20-45 years old). Extrapulmonary tuberculosis cases (37%) have become almost as frequent as pulmonary tuberculosis forms (42.8%) among HIV positive patients, and the clinical picture is often atypical. Tuberculosis morbidity is increasing annually because of AIDS. The longer the tuberculosis patients with AIDS remain in the hospital, the fewer beds are available for other patients. For the public health programs against AIDS in developing countries, this is becoming an urgent problem to resolve.

[Toxoplasmosis and cytomegalovirus serology in patients infected with HIV in Congo]. / Sérologie de la toxoplasmose et du cytomégalovirus des malades infectés par le VIH au Congo.

Cerebral toxoplasmosis and cytomegalovirus (CMV) infection are very frequent in AIDS. Biological markers of toxoplasmosis and CMV were studied in blood and cerebrospinal fluid (CSF) of 121 HIV-positive and 35 HIV-negative patients in the Central Hospital of the Congolese Army in Brazzaville. In the case of clinically suspected cerebral toxoplasmosis, the simultaneous presence of specific IgG antibodies in the blood and in the CSF can be considered as having complementary diagnostic value (PPV = 63.3%, NPV = 89.9%). The symptomatology of AIDS is very polymorphous and includes various etiological factors; as a result it is very difficult to estimate the responsibility of cytomegalovirus in the absence of positive viral culture, even with the simultaneous presence of specific IgG antibodies in the blood and CSF (PPV = 75.7%, NPV = 54.6%).

[Retrospective study of infection by the human immunodeficiency virus in pregnant women. Future of the child and the mother]. / Etude rétrospective de l'infection par le virus de l'immunodéficience humaine chez la femme enceinte. Devenir de l'enfant et de la mère.

5.4% (108 of 2,000) women have been confirmed for HIV 1 infection in Brazzaville in 1987. 1,172 deliveries have been registered by study, 7.76% have been occurred in HIV+ women. The prevalence of miscarriages was significantly, higher in HIV+ women than in HIV- ones (p less than 0.001). The birth-weight of new-borns was not significantly different among the children born to HIV+ and HIV- mothers. There were the various probable reasons of death of children born to HIV+ mothers. More frequently the respiratory affections with persistent hyperthermia were noticed. During the follow-up, in all groups of age, the fever with failure of thrive were the most frequent signs (50%) with pneumopathy. The clinical picture was completed by diarrhoea after six months of live.

[Clinical and developmental aspects of acquired immunodeficiency syndrome in the Congo (the experience of the medical service of the Hôpital Central des Armées Pierre Mobengo - Brazzaville)]. / Aspects cliniques et évolutifs du syndrome d'immunodépression acquise au Congo (expérience du service de médecine de l'Hôpital Central des Armées Pierre Mobengo - Brazzaville).

During a period of 20 months, 204 cases of AIDS were diagnosed among adults in the Medicine Department of the Pierre Mobengo Armed Forces Central Hospital, Brazzaville. The authors review the clinical and evolutive aspects in admitted patients during these period of time, taking into consideration the problems of diagnosis, treatment and monitoring, according to the conditions of practice. Individuality of AIDS in Central Africa is underlined by its different features. AIDS strikes heterosexual people with multiple partners, with a sex-ratio near to 1. In a patient more often cachectic and febrile, some digestive manifestations occurred, mainly diarrheal, early, neurological, of bad prognosis. Pulmonary manifestations (above all tuberculosis superinfection) and cutaneous manifestations often characteristic, are less frequent and mainly different from the ones observed in Europe and North America. Fast evolution is underlined. These characteristics of AIDS in Central Africa, of course subordinate to the medical context, seem mainly linked to a peculiarity of the disease, in close relationship with the density of the infection, diathesis and opportunistic environment, all very different.