Cross-clade immune responses to Gag p24 in patients infected with different HIV-1 subtypes and correlation with HLA class I and II alleles.

Individuals infected with different subtypes of HIV-1 (A, B, C, D, CRF01_AE and CRF02_AG) were analyzed for their antigen-specific immune response with respect to their HLA genetics. The p24 Gag protein was selected for analysis, since previous studies of the same cohort of patients had shown that almost 80% of these individuals responded to Gag peptides of subtypes A, B and/or C. A large number of Gag antigen-specific responses were recorded. Both previously recognized as well as new epitopes were identified, assumed to bind HLA classes I and/or II. Fifteen individuals showed class I cellular responses to T cell epitopes irrespective of the infecting virus subtype. For five individuals infected with subtypes A, B, D and CRF02_AG, new T cell epitopes are described. Responses related to the patient's class I alleles are frequent, and several new putative class II responses were found.

Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure.

OBJECTIVES: The aim of the study was to investigate the presence of M184I/V in minor HIV-1 populations of patients who failed lamivudine (3TC) and/or didanosine (ddI) treatment. MATERIALS AND METHODS: Fourteen 3TC-experienced patients who, after switching therapy to a ddI regimen, had a new failure without M184I/V in the major viral population were included in the study. Ninety plasma samples were analysed by direct sequencing and selective real-time polymerase chain reaction (SPCR), which detects GTG/GTA and ATA mutants down to 1 and 0.2% of the population, respectively. RESULTS: In five samples, SPCR detected resistant virus when direct sequencing detected wild-type M184. In patients with mixed viral populations at sequencing, the median proportion of mutants detected by SPCR was 30%. SPCRGTG reactivity dominated, while SPCRATA reactivity only was uncommon. M184I/V disappeared in patients in whom 3TC was stopped but ddI continued. Ten patients with ddI failure had no M184I/V. CONCLUSIONS: Minor HIV-1 strains may harbour M184I/V in patients failing ddI therapy, despite direct sequencing showing wild-type virus. Although M184I/V may reduce the genetic barrier of ddI for mutations such as K65R and L74V, the lack of re-emergence of M184I/V in the minor quasispecies of most patients who failed ddI suggests that M184I/V was not a preferred route to ddI resistance in our patient population.

HIV-1 in placentas of untreated HIV-1-infected women in relation to viral transmission, infectious HIV-1 and RNA load in plasma.

The presence of HIV in the placenta was analysed in relation to virological and immunological factors and vertical transmission of HIV in 39 pregnancies between 1989 and 1993 among 37 HIV-1-infected women without zidovudine prophylaxis. HIV-1 was detected in 12 of 37 (31%) placentas by immunohistochemistry and in 3 of 18 by PCR. Altogether 14/39 (36%) placentas bore evidence of HIV-1 infection, although there was no relation with the outcome of HIV infection in the child. Neither was there a relation between placental infection and either CD4 cell counts or HIV-1 RNA levels. However, HIV-1 was isolated from plasma in 20 of 39 (50%) pregnancies, which was inversely related to the presence of HIV in the placenta. When HIV-1 was identified in the placenta, HIV-1 was isolated from plasma in 3/14 (21%) pregnancies, vs 17/25 (68%) when it was not (p = 0.01), with a relative risk of having a placenta positive for HIV of 3.9 in pregnancies with a negative plasma HIV isolation. This inverse relation may point to differences in tropism between HIV-1 in placenta and plasma. The results show that the placental barrier prevents HIV transmission, irrespective of whether HIV enters the placenta or not.

Gender differences in perceived health-related quality of life among patients with HIV infection.

This article explores how a group of human immunodeficiency virus (HIV)-infected patients perceived their health-related quality of life (HRQOL) in relation to their coping capacity expressed as sense of coherence. The emphasis was on gender differences. The sample consisted of 55 women (29%) and 134 men (71%), receiving outpatient medical care in a hospital. Self-report instruments, the health index, the HIV symptom scale, the well-being scale, the sense of coherence (SOC) scale and the Interview Schedule for Social Interaction were used. Disease status (HIV CDC classification, absolute CD4+ lymphocyte count and HIV/RNA) was also measured, and demographic data were collected. The total sample scored significantly worse self-rated health and weaker SOC than healthy controls. The HIV-infected women were significantly younger than the men (p < 0.0001). The majority of the women (60%) were infected by heterosexual transmission and of the men (58%) by homosexual/bisexual contacts. In the univariate analysis the women scored significantly less positive well-being (p < 0.05), weaker SOC (p < 0.05), and less social support (p < 0.01) than the men despite less advanced disease. Multiple regression analyses revealed that SOC was the strongest predictor of subjective HRQOL in both genders. The results suggest that health professionals who individualize their care of HIV-infected patients should try to be sensitive to the different ways in which men and women express their HRQOL.

[Mother-to-child transmission of HIV infections. Antiviral agents and Cesarean section reduce the risk of transmission]. / HIV-smitta från mor till barn. Läkemedel och kejsarsnitt minskar risk för smitta.

There has been a substantial decrease in maternal-infant transmission of HIV in many European and North American countries during the past five years, from 15-25 per cent to approximately 5%. Reasons include the prophylactic administration of zidovudine to mother and child, more effective treatment strategies leading to decreased viral load during pregnancy, and increased use of elective Caesarean section. In developing countries however, the vertical transmission rate of HIV is still high at 25-40 per cent. Simpler and less expensive prophylactic regimens, such as nevirapine to mother and child at delivery and after birth, respectively, have raised hope. Drug resistance and the risk of adverse effects of antiretroviral drugs on the child are threats to the prevention of mother-to-infant transmission of HIV.

Cross-reactive T-helper responses in patients infected with different subtypes of human immunodeficiency virus type 1.

Immunization with a recombinant glycoprotein 160 envelope immunogen derived from a virus of genetic subtype B induced strong specific T-helper cell responses in asymptomatic human immunodeficiency virus (HIV) carriers infected with subtypes B to G. This indicates that the HIV-specific T-helper immunity, which is the basis for development of antibodies and cytotoxic T lymphocytes, can be improved by both homologous and heterologous antigens. It also suggests that a particular immunogen can be effective against many different HIV strains.

Similar rate of disease progression among individuals infected with HIV-1 genetic subtypes A-D.

OBJECTIVE: HIV-1 is characterized by a high degree of genetic variation and can be divided into at least 10 distinct genetic subtypes. The purpose of this study was to investigate whether the rate of disease progression shows subtype-specific differences. DESIGN: The investigation was divided into two parts; one study in which 49 ethnic Africans were compared with 49 ethnic Swedes irrespective of the subtype of the infecting virus, and a second study in which 126 individuals infected with different genetic subtypes (28 with subtype A, 59 with subtype B, 21 with subtype C and 18 with subtype D) were compared. METHODS: CD4 cell counts, the rate of CD4 cell decline, plasma HIV-1 RNA levels, clinical status and antiviral treatment were prospectively and retrospectively recorded. The HIV-1 subtype had previously been determined by direct sequencing of the V3 domain of the env gene. RESULTS: There were no significant differences in the rate of CD4 cell decline or clinical disease progression between Africans and Swedes over an observation period of 2 years. Similarly, there were no differences in the rate of CD4 cell decline, clinical progression or plasma HIV-1 RNA levels between individuals infected with subtypes A, B, C or D over a mean observation period of 44 months. CONCLUSION: Neither the genetic subtype of the virus nor the ethnicity of the host appear to be major determinants of disease progression.

[Current treatment of HIV infection]. / Aktuell behandling av HIV-infektion.

The treatment of HIV infection in the industrialised countries has undergone manifest changes during the past decade. Since the advent of zidovudine in 1987, the first agent capable of delaying disease progression, several other nucleoside analogues have been introduced, though in retrospect the effect of these drugs can now be seen to have been moderate. With the introduction of proteinase inhibitors, more effective control of infection became possible, and the combination of a proteinase inhibitor with two nucleoside analogues yielded a triple-drug treatment capable of halting progression for a large proportion of patients. Thus, during recent years the disease course has changed in character from successive deterioration of the immune defence system to a condition where most patients can live virtually normal lives in many respects. For some patients, however, the new drugs have been associated with side effects, and our knowledge of the long-term effects is still insufficient.

Subtype-specific problems with quantification of plasma HIV-1 RNA.

OBJECTIVE: To determine whether two commercial assays for quantification of plasma HIV-1 RNA levels detect different genetic subtypes of HIV-1 with equal efficiency. DESIGN: Blind testing of stored plasma samples from 95 individuals infected with different genetic subtypes of HIV-1 (27 subtype A, 24 B, 18 C, 18 D, two E, two G, two H, and two J). The HIV-1 subtype had previously been determined by direct sequencing of the V3 domain of the env gene. METHODS: One plasma sample from each individual was tested once by the Roche HIV monitor assay and once by the Organon nucleic acid sequence-based amplification (NASBA) HIV-1 RNA quantitative assay, according to the manufacturers' recommendations. Information about CD4+ lymphocyte counts and antiretroviral treatment was available. RESULTS: The results from the two assays were strongly correlated with each other for subtypes B, C and D, but not for subtype A because many samples had RNA levels close to or below the lower detection limit of the assays. Thus, 15 out of 27 (56%) subtype A samples were negative by the HIV monitor assay and 12 (44%) were negative by the NASBA assay. These frequently occurring negative results among subtype-A-infected individuals were not due to better immunological status, more aggressive antiretroviral treatment, or differences in sample storage conditions. CONCLUSIONS: The HIV monitor assay and, possibly to slightly lesser degree, the NASBA assay appear unable to accurately quantify HIV-1 RNA levels in plasma samples from many subtype-A-infected individuals. These problems are likely to be due to primer mismatches and they limit the possibility of using these assays for routine monitoring of HIV-1-infected individuals in many parts of the world.

Most HIV-1 genetic subtypes have entered Sweden.

OBJECTIVE: The aim of this study was to document which genetic subtypes of HIV-1 have entered Sweden and to study transmission patterns of these virus variants. PATIENTS: All HIV-1 infected individuals at Danderyds Hospital, Stockholm, Sweden, who were suspected of carrying a virus of African origin were prospectively included in the study. The study subjects originated from 15 different African countries. METHODS: The V3 domain of the HIV-1 envelope was directly sequenced from uncultured peripheral blood mononuclear cells from 75 individuals included in the study. Phylogenetic analyses were used to determine genetic subtype and to study transmission patterns. RESULTS: The virus strains carried by the study subjects belonged to six established subtypes of HIV-1 (27A, 4B, 18C, 18D, 2G, 2H). Two individuals from Zaire carried a subtype, which had not been classified previously, provisionally named subtype 1. Eleven transmissions of non-subtype B strains in Sweden were documented. CONCLUSIONS: This study shows that most genetic HIV-1 subtypes have entered Sweden despite the relatively low prevalence of HIV infection in the country. Thus, the complete dominance of subtype-B infections which was seen during the early phase of the HIV-1 epidemic in Europe and the US has been broken in Sweden.

[The year of the world aids day: children in a world of AIDS]. / Arets världsaidsdag: barn i en värld med aids.

PIP: "Children living in a world with AIDS" was the theme of a UNAIDS campaign launched because 1 million children are infected with HIV and 9 million children have become orphans due to AIDS (90% in sub-Saharan Africa). During 1996 alone, 400,000 children were infected: 90% were infected during pregnancy, delivery, or while breast feeding; the remaining 10% were infected sexually or via blood or blood products. In Africa, only one-third of HIV-infected children survive their 3rd birthday, and 8% of all children in Zimbabwe have lost their mothers to AIDS. A similar situation is rapidly evolving in Asia and South America. In Spain and Italy, more than 600 children have AIDS; most of them were infected through drug-abusing mothers. In France the figure is comparable, but here a large segment is represented by children of mothers from African countries. The total number of children with AIDS in the European Community is 2800: 86% were infected through their mothers. Romania has 4000 children with AIDS, who were predominantly infected via nonsterile syringes and blood transfusion. The European Commission has a specific AIDS prevention program, which addresses the measurement of disease spread, counteracting the disease, information and education, support for persons with HIV/AIDS, and countering discrimination. The risk of mother-to-child HIV transmission can be reduced from 25% to 8% by zidovudine (AZT) treatment during pregnancy and delivery.^ieng

Prevention of hepatitis B by immunization of the newborn infant--a long-term follow-up study in Stockholm, Sweden.

In order to assess the present hepatitis B immunization program in Stockholm, Sweden, 212 children of HBsAg carrier mothers were followed up 2-9 years after birth. In babies of HBeAg-positive mothers a combined passive and active immunization schedule with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine was used. Among 25 children to such mothers, 1 HBsAg carrier and 5 children with asymptomatic seroconversion were found. To newborns of HBeAg-negative/anti-HBe-negative mothers, only vaccine was given. Among 15 such children, no HBsAg carrier (but 1 child with an asymptomatic seroconversion) was found. In babies of HBeAg-negative/anti-HBe-positive mothers, immunization was withheld between 1983 and 1987. Among 90 such children, 1 HBsAg carrier and 8 asymptomatic seroconversions were detected. After 1987, newborns in this group were vaccinated whereafter 3 asymptomatic seroconversions were found among 82 children. We conclude that in low prevalence areas a screening program for HBsAg should be offered to pregnant women originating from hepatitis B endemic regions, since immunoprophylaxis gave long-term protection to most children at risk. Children born to HBeAg-positive mothers should receive vaccine in combination with HBIg, whereas for children of mothers lacking HBeAg, vaccination only seems sufficient, at least if a rapid vaccination schedule is used.

Somatic care wanted by HIV-infected intravenous drug abusers: the patients' opinions and experiences.

The somatic care of HIV-infected intravenous drug abusers (IVDUs) is often combined with many problems. The addict is often an unpopular patient, but society must assume responsibility for him or her and it is important to solve care problems in an appropriate way. This study was undertaken in order to investigate what kind of care addicts want when they become somatically ill. A questionnaire was given to patients who acquired HIV infection due to intravenous drug abuse, who visited an outpatient clinic for HIV-infected patients at the Department of Infectious Disease, Huddinge Hospital, Stockholm, Sweden. A total of 72 of the original 78 questionnaires could be evaluated. Thirty respondents took part in the Stockholm Methadone Programme. The patients were asked to rank the importance of professional competence among the staff. The patients ranked competence in pain treatment highest followed by competence in somatic medical care. Lower ranked, but still perceived as important, was competence in psychiatric medical care and social welfare work. Experience in treatment of addiction was ranked as less important. It can be concluded that it is fruitful to ask IVDUs about their preferences concerning care.

[Children of HIV-infected women. An exposed group]. / HIV-infekterade kvinnors barn. En utsatt grupp.

PIP: In order to describe the social situation of children of HIV-infected mothers, an investigation was carried out between November 1991 and February 1992. A questionnaire inquiring about children (under 18) of HIV-infected mothers was sent out to all HIV treatment wards in Stockholm and institutes engaging in family and social care. The mothers (21-45 years old, average age 32 years) were divided into 4 groups: 1) known or probable infection through sexual contact in Europe (mainly in Sweden), 2) known or probable infection through sexual contact in the rest of the world (mainly in Africa), 3) infection via blood products, and 4) infection via intravenous drug abuse. Data were received about 92 living mothers and their 144 children under 18 years of age. Almost two-thirds of the mothers' infection were known to be or probably sexually transmitted, and of these more than two-thirds were from countries outside Europe, mainly from Africa. Only 32% of mothers were infected by IV drug use, and the remaining 6% via blood products. 24% of all children had mothers with an advanced stage of the disease (AIDS or severely reduced immune response). All children 11-18 years old were HIV negative, while 10 children of 105 who were under 11 years of age were infected with HIV, and 15 had a still undetermined HIV status. In all, 63% (91/144) of children had a known living father, 40% of whom (36/91) were infected with HIV. 40% of all children (58/144) had regular contact with their fathers, while only 1 child of 20 children who were under guardian care had regular contact. 74% of the children faced the risk of being left without parents.^ieng

[Reasons for HIV testing. Casual sexual contacts are the most common reasons for voluntary HIV testing]. / Orsaker till HIV-test. Sexuell kontakt vanligaste skälet till frivillig testning.

In Sweden, voluntary testing for HIV (human immunodeficiency virus)-antibodies has been given an important place in combating AIDS (acquired immunodeficiency syndrome). To elicit the reasons why people seek voluntary testing on their own initiative outside general screening programmes, during a three-year period (1989-91) applicants at a major urban testing locale were asked to fill in an anonymous questionnaire, which was completed by 68.6 per cent (831/1,212) of those eligible. Of the 831 respondees (both men and women), 88.9 per cent cited recent casual sexual contact as the reason why they might be at risk. Although in most cases no particular risk factors were reported to be associated with the sexual contact, in 17 cases (2.3 per cent) the partner was known to be an HIV-carrier. Of 664 people completing the item on the questionnaire 208 (31.3 per cent) reported the sexual contact to have occurred abroad. When the reason for undergoing the test was not possible recent exposure, the commonest reasons given were persistent anxiety or the establishment of a new sexual relationship. Only one of the 1,212 tests performed was HIV-positive.

Screening for HIV-1 antibodies in pregnancy: results from the Swedish national programme.

OBJECTIVE: To determine the effectiveness of a national screening programme for HIV infection in pregnant women. DESIGN: Observational study. SUBJECTS: All pregnant women presenting to antenatal or abortion clinics. SETTING: Sweden, September 1987 to December 1991. MAIN OUTCOME MEASURES: Number and characteristics of infected women. RESULTS: By the end of the study period 510,000 tests had been performed and 54 women with HIV infection identified (1.06/10,000). Of the 33 women identified in Stockholm, 14 women (4.4/10,000) had attended abortion clinics and 19 antenatal clinics (1.8/10,000; p < 0.05). Three women had been intravenous drug users, one was infected through a blood transfusion, and 50 were probably infected sexually. Of the 20 women who attended antenatal clinics early enough to allow an abortion, 12 continued with their pregnancies. CONCLUSIONS: Testing of all women, not just those perceived to be at risk, probably contributed to the high uptake of HIV testing. With high uptake such screening provides valuable data on spread of HIV in the heterosexual population and presents opportunity for preventing transmission of HIV to children and partners.

Evaluation of HIV testing in Sweden, 1985-1991.

OBJECTIVE: Evaluation of the extent and outcome of HIV testing in Sweden. DESIGN: Data from screening programmes, laboratory and clinical reports were compared and a national survey on HIV testing was performed. RESULTS: The proportion found to be positive in screening of blood donors, pregnant women and sexually transmitted disease patients were approximately 1/100,000, 1/10,000 and 1-2/1000, respectively. One-quarter of the men and one-third of the women in Sweden aged 16-74 years reported that they had been tested for HIV at least once. CONCLUSION: There is a high cost involved in detecting HIV-infected individuals through general testing. This cost can be justified if we believe that awareness of an infection substantially reduces the risk of further transmission.

Design and pharmacokinetics of Logimax, a new extended-release combination tablet of felodipine and metoprolol.

A new, once-daily combination tablet containing felodipine and metoprolol has been developed, using extended-release techniques to obtain even plasma concentrations throughout the dosing interval. The tablet consists of a hydrophilic matrix containing felodipine in which many small membrane-coated metoprolol pellets are embedded. On contact with gastrointestinal fluids, felodipine is released at an almost constant rate by erosion of the hydrophilic matrix. The release of metoprolol also follows near zero-order kinetics, and is mainly controlled by diffusion through the membrane covering each individual metoprolol bead. Smooth plasma concentration profiles are obtained for both drugs of the combination, similar to those found with the corresponding single-drug formulations: felodipine extended-release tablets and metoprolol controlled-release tablets. The new fixed combination tablet also consistently provides even plasma concentrations of felodipine and metoprolol after administration together with food and in elderly hypertensive patients. The convenience of one tablet per day for effective antihypertensive treatment with a combination of felodipine and metoprolol should improve patient compliance with the prescribed regimen.