Reductions in viral load and increases in T lymphocyte numbers in treatment-naive patients with advanced HIV-1 infection treated with ritonavir, zidovudine and zalcitabine triple therapy.

In order to test the hypothesis that a combination of protease inhibitors with nucleoside analogues-agents known to inhibit different steps of the human immunodeficiency virus (HIV) life cycle--is likely to prove more effective in reducing viral loads than either of those modalities alone, we performed a 60 week, open-label trial in 32 HIV-positive patients with depressed CD4 T lymphocyte cell counts but no active AIDS-defining illnesses. For the first 2 weeks, patients received 600 mg twice daily of liquid ritonavir, a protease inhibitor; then zidovudine 200 mg three times daily and zalcitabine 0.75 mg three times daily were added to the treatment regimen. Mononuclear blood cell fractions were analysed for infected cell levels, using a co-culture system. HIV-1 RNA in plasma was measured both by reverse transcriptase-polymerase chain reaction (RT-PCR) and reverse transcriptase quantitative PCR (QcRT-PCR); lymphocyte counts were determined by standard laboratory methods. In the 2 weeks of ritonavir therapy, both the mean count of infectious blood cells and plasma HIV RNA levels decreased dramatically. Mean CD4 cell counts increased from 173 cells/mm3 at baseline to 286 cells/mm3; CD8 cell counts rose from 951 cells/mm3 to 1,141 cells/mm3. With the introduction of the nucleoside analogues, infectious cell counts and plasma virus dropped another log unit to a nadir at 8 weeks, while CD4 T lymphocyte counts continued to rise slowly. By week 28, 12 patients had withdrawn due to adverse events, none of which were life-threatening. At week 36, infectious material could not be detected in the cells of 10 of the 17 remaining patients; by week 60, four of the seven patients with residual viraemia at week 24 had undergone viral relapse. After the introduction of a more palatable capsule formulation of ritonavir at week 52, infectious cells and plasma virus were undetectable in 50-60% of patients. The combination of protease inhibitors and nucleoside analogues significantly reduces HIV load, and in some patients may suppress viral activity for sustained periods.

Hepatitis B surface antigen (Australia antigen) in mosquitoes collected in Senegal, West Africa.

During July and August of 1973, 9,198 mosquitoes were collected in the Republic of Senegal. Eight species of mosquitoes were found in the collections: Culex thalassius, Culex pipiens quinquefasciatus, Culex trigripes, Culex phillipi, Aedes irritans, Aedes aegypti, Anopheles gambiae, and Mansonia sp. Specimens were sorted by biological condition; those obviously engorged were designated as (E), females with swollen abdomens not conspicuously blooded were considered gravid (G), and those with normal or shrunken abdomens were considered neither blooded nor gravid (U). Representative samples of each species were tested by solid phase radioimmunoassay for hepatitis B surface antigen (HBSAg, Australia antigen). A total of 12 mosquitoes were found to be HBSAg positive out of 1,658 individuals tested. These were: 9 Culex thalassius, 1 (E), 5 (G), 3 (U); 2 Culex pipiens quinquefasciatus, 1 (E), 1 (U); and Aedes irritans, 1 (U).

[Hepatic involvement in the acquired immunodeficiency syndrome. Study of 20 cases]. / Atteintes hépatiques au cours du syndrome d'immunodépression acquise. Etude de 20 cas.

Liver biopsies were systematically performed in 20 patients with evidence of an acquired immunodeficiency syndrome (18 with opportunistic infections, 9 with Kaposi's sarcoma). Hepatitis, related to hepatitis-B virus in 3 cases and to cytomegalovirus in 3 cases, was present in 6 of them. All patients had at least one of the three following lesions: non-specific portal inflammatory infiltration (6 cases), granulomatous lesions (12 cases), vascular abnormalities (12 cases). Among hepatic granulomatous lesions: 3 were due to acid-fast bacilli and 1 to Cryptococcus. Sinusoidal abnormality included proliferation of Küpffer cells (9 cases), sinusoidal dilatation (2 cases), peliosis (4 cases) and Kaposi's sarcoma (1 case). A relationship between these abnormalities cannot be excluded.

[Acquired immunodeficiency syndrome in 4 homosexuals]. / Syndrome d'immunodépression acquise chez 4 homosexuels.

Two young homosexual men apparently without any obvious cause of immunosuppression suddenly developed a series of opportunistic infections. Two others presented with prolonged fever and multiple lymph node enlargement of obscure origin. Immunological investigations in these 4 patients showed skin anergy and inversion of helper/suppressor lymphocyte ratio. Proliferative responses to mitogenic agents, soluble antigens and allogenic cells were altered only in the 2 patients with opportunistic infections. Humoral immunity seemed to be preserved in all cases. These 4 patients had previously suffered from many sexually-transmitted infections, had spent some time in the United States and had signs of past or present cytomegalovirus infection. As in the U.S.A., where this "acquired immunodeficiency syndrome" suddenly developed during the past 2 years, one may suspect, among several hypotheses, that it is caused by a transmissible agent now present in France.

[Inguinal mycetoma caused by A. pelletieri. Apropos of a case]. / Mycétome inguinal à A. pelletieri. A propos d'une observation.

This work is a report of a new case of A. pelletieri inguinal mycetoma probably of primary localization. This ganglionary localization may be responsible for therapeutic failures and a regular survey is needed after a partial surgical cure was done.

Cryptococcus neoformans antibody levels in patients with AIDS.

Anti-Cryptococcus neoformans capsular polysaccharide (CPS) antibodies were measured by ELISA in patients with AIDS related complex or AIDS without a known history of cryptococcosis and in heterosexual healthy controls. Total and IgG anti-CPS antibody activity was rarely detected in patients, with mean levels lower than in controls, whereas IgM antibody activity was similar in the 3 groups. Since both humoral and cellular immunity appear to be of great importance during cryptococcosis, the inability of AIDS patients to synthetize specific IgG antibodies could impair an alternative host defence mechanism to cellular immunity.

[The Duffy blood group in migrants of French-speaking Africa]. / Le groupe sanguin Duffy chez les migrants d'Afrique francophone.

The Duffy blood types survey in 544 subjects coming from French speaking African countries, shows the high percentage of subjects having a Duffy a- b- blood type (94%). It ought to be emphasized that this predominantly Duffy a- b- population resides in areas in where there is according to the WHO data, a very low incidence of Plasmodium vivax invasion. Moreover, we have taken for another example North Vietnam, an area where there is a large Plasmodium vivax invasion and where we have found a small percentage of Duffy negative subjects (5.6%). In agreement with many authors reporting an association between Duffy negatively and vivax malarial refractoriness, this survey demonstrate that in French speaking African areas where there is a very low incidence of Plasmodium vivax invasion we have found, as expected, a high rate of Duffy negative subject.

Host responses to hepatitis-B infection in patients with primary hepatic carcinoma and their families. A case/control study in Senegal, West Africa.

A case/control study of patients with primary hepatic carcinoma (P.H.C.) and their families was carried out in Dakar, Senegal. 28 P.H.C. cases were matched by age,sex, and ethnic group with 28 controls. Serum was collected from cases, controls, parents (28 mothers, 27 fathers) of cases, parents of controls, 71 siblings of cases, and 58 siblings of controls. Assays of their sera for hepatitis-B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis-B core antigen (anti-HBc) produced the following results. (1) Nearly all P.H.C. cases (97%) and controls (93%) had some evidence of infection with hepatitis-B virus (H.B.V.), but the cases were more likely to be anti-HBc(+) and less likely to be anti-HBs(+) than the controls. (2) Most of the mothers of the cases were HBsAg(+) (71%), whereas only 14% of the mothers of controls were HBsAg(+). Lover titres of anti-HBs were less common in the mothers of the cases. (3) None of 27 fathers of cases had detectable anti-HBs, but 13 (48%) of the fathers of controls were anti-HBs(+). (4) Siblings of the P.H.C. cases were more likely to have anti-HBs than either their sibs with P.H.C. or the sibs of the controls. However, sibs of P.H.C. cases had lower titres of anti-HBs than the sibs of the controls. These data are consistent with the hypothesis that the P.H.C. cases were infected with H.B.V. by their mothers and that there was an environmental factor which affected the immunological response of all family members to H.B.V. Infection with H.B.V. and the mode of response to that infection among members of families appear to be major factors in the aetiology of P.H.C. in West Africa.

Circulating immune complexes in six patients with trichinosis.

The sera of six patients infected with Trichinella spiralis were studied for the presence of circulating immune complexes (CIC). CIC were present in all six patients studied 1 month after infection. In two patients in whom serial serum samples were available, as clinical improvement occurred there was a decrease in the level of CIC and an increase in the fluorescent antibody titres.

[Immune complexes and complement in leprosy (author's transl)]. / Les complexes immuns et le complément dans la lèpre.

The sera of 87 Senegalese patients with various forms of leprosy were investigated. Two of the most reliable methods were used to detect circulating immune complexes : the radiolabelled C1q binding test and the Raji cell binding technique. Several fractions of complement, including C3, C4, factor B and the C3d product of C3 were also assayed. A material having the properties of immune complexes was detected in lepromatous and reactional leprosy. In tuberculous leprosy, only the Raji cell binding technique gave positive results. C3 and C4 were normal or slightly raised, but C3d was increased in all forms of the disease. There was no significant correlation between C3d values and the results of immune complexes detection tests.

[Cost of transfusion in AIDS. Experience at the Claude-Bernard Hospital apropos of 28 cases]. / Coût transfusionnel du SIDA. Expérience de l'hôpital Claude-Bernard à propos de 28 cas.

The study of 28 confirmed cases of AIDS shows that transfused patients use a large amount of hospital's blood products, especially platelets. For these patients, the average cost of transfusion is higher than that, for intensive care unit patient's. The use of irradiated products increases the cost (+ 35%). As there is a shortage of donors, if the present precautions are respected, there is no reason why the hospital should not continue to ask the patient's family and circle of friends, to donate blood.

[The relation of infection with the hepatitis B-agent to primary hepatic carcinoma (author's transl)]. / Hepatitis B-Infektion und primäres Leberkarzinom

In Asia, Africa and other tropical areas primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the post-necrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 PHC patients had hepatitis B surface antigen (HBSAg) (controls: 8 of 98) and 56 of 63 (controls: 26 of 100) had antibody against hepatitis B core antigen (anti-HBC). In earlier studies we demonstrated a maternal effect of HBSAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBSAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; p = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBSAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the African hepatoma patients showed that there is a very high frequency of HBSAg in mothers (71.6%) while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. We described a vaccine several years ago which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.

The relation of infection with the hepatitis B agent to primary hepatic carcinoma.

In Asia, Africa, and other tropical areas, primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the postnecrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 patients with PHC had hepatitis B surface antigen (HBsAg) (controls, 8 of 98) and 56 of 63 (controls, 26 of 100) had antibody against hepatitis B core antigen (anti-HBc). In earlier studies, we demonstrated a maternal effect of HBsAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBsAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; P = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBsAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the west African hepatoma patients showed that there is a very high frequency of HBsAg in mothers (71.6%), while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. Several years ago, we described a vaccine which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis, and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.