Southern ocean carbon and heat impact on climate.

The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Qualitative exploration of perceived benefits of care and barriers influencing HIV care in trans Nzoia, Kenya.

BACKGROUND: Substantial efforts have been made to ensure people living with HIV (PLHIV) are linked to and retained in care but many challenges deter care utilization. We report perceived benefits of seeking HIV care and barriers to HIV care that were identified through a formative assessment conducted to advise the development of an alternative care model to deliver antiretroviral treatment therapy (ART) in Trans Nzoia County, Kenya. METHODS: Data were collected in 2015 through key informant interviews (KIIs), in-depth interviews (IDIs), and focus group discussions (FGDs). The study involved 55 participants of whom 53% were female. Ten KIIs provided community contextual information and viewpoints on the HIV epidemic in Trans Nzoia County while 20 PLHIV (10 male and 10 female) participated in IDIs. Twenty-five individuals living with HIV participated in four FGDs - two groups for men and two for women. Key informants were purposively selected, while every third patient above 18 years at the Kitale HIV Clinic was invited to share their HIV care experience through IDIs or FGDs. Trained research assistants moderated all sessions and audio recordings were transcribed and analyzed thematically. RESULTS: Findings showed that PLHIV in Trans Nzoia County used both conventional and complementary alternative care for HIV; however, public health facilities were preferred. Popular perceived benefits of adopting care were relief from symptoms and the chance to live longer. Benefits of care uptake included weight gain, renewed energy, and positive behavior change. Individual-level barriers to HIV care included lack of money and food, use of alternative care, negative side effects of ART, denial, and disclosure difficulties. At the community level, stigma, limited social support for conventional HIV treatment, and poor means of transport were reported. The health system barriers were limited supplies and staff, long distance to conventional HIV care, and unprofessional providers. CONCLUSIONS: Diverse individual, community and health system barriers continue to affect HIV care-seeking efforts in Kenya. Appreciation of context and lived experiences allows for development of realistic care models.

Occurrence of an incomplete C8 molecule in homozygous C8 deficiency in man.

Sera from unrelated individuals with recurrent Neisserial infections lacked C8 hemolytic activity, but contained a protein that is antigenically related to C8. Immunochemical analysis revealed complete identity of the C8-related protein of all three sera and a marked antigenic deficiency compared with normal C8. The C8-related protein was isolated from serum by adsorption to immobilized anti-C8 IgG, elution with 3 M guanidine, and subsequent gel filtration. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the abnormal protein resembled the alpha-gamma subunit of normal C8 with respect to mobility and its ability to be cleaved upon reduction into the alpha and gamma chains. The beta chain present in normal C8 was absent. Sedimentation equilibrium analysis indicated a molecular weight of 86,000 for the abnormal C8 protein, which is identical to that of the alpha-gamma subunit of normal C8. Amino acid analysis revealed no significant difference between the abnormal C8 and normal alpha-gamma. Unlike normal C8, the abnormal protein did not bind to EAC1-7 or to SC5b-7; however, upon addition to the deficient serum of beta chain isolated from normal C8, hemolytic activity was restored and formation of SC5b-9 occurred. We concluded that the dysfunctional C8 protein in the three individuals' serum is identical to the alpha-gamma subunit of normal C8 and that this form of C8 deficiency is distinct from the C8 deficiencies previously reported in which the entire three-chain protein is lacking.

Transfusion-associated AIDS: serologic evidence of human T-cell leukemia virus infection of donors.

An assay for antibodies to membrane antigens of cells infected by human T-cell leukemia virus was used to examine serum from persons who donated blood to 12 patients with acquired immunodeficiency syndrome (AIDS) associated with blood transfusions. The occurrence of positive results in the assay was significantly greater among donors to the AIDS patients (9 of 117; 7.7 percent) than among random donors (1 of 298; 0.3 percent). Of 12 sets of donors examined, 9 sets included a donor whose serum gave positive results for the presence of the antibodies. In six of these nine sets, the seropositive donor was an individual who was also identified as a possible source of AIDS transmission when epidemiologic and immunologic criteria were used.

Antibodies to the core protein of lymphadenopathy-associated virus (LAV) in patients with AIDS.

Lymphadenopathy-associated virus ( LAV ), a human T- lymphotrophic retrovirus isolated from a homosexual man with lymphadenopathy, has been causally associated with acquired immunodeficiency syndrome (AIDS). A sensitive and specific radioimmunoprecipitation test was developed for the detection of antibodies to the major core protein of LAV , p25 (molecular weight 25,000). Antibody to LAV p25 was found in the serum of 51 of 125 AIDS patients, 81 of 113 patients with lymphadenopathy syndrome, 0 of 70 workers at the Centers for Disease Control (some of whom had handled specimens from AIDS patients), and 0 of 189 random blood donors. Of a group of 100 homosexual men from San Francisco whose serum was obtained in 1978, only one had antibody to LAV p25; in contrast, of a group of 50 homosexual men in the same community whose serum was obtained in 1984, 12 had antibodies to LAV p25.

Alternative algorithms for human immunodeficiency virus infection diagnosis using tests that are licensed in the United States.

Serodiagnosis of human immunodeficiency virus (HIV) infection in the United States has traditionally relied on a sequential two-test algorithm: an initial screen with an enzyme immunoassay (EIA) and reflex testing of EIA-reactive specimens with a more specific supplemental test such as Western blotting or immunofluorescence. The supplemental tests are tedious, subjective, and expensive. In addition, there have been major improvements in the performance and accuracy of the EIA tests as well as the introduction of rapid serologic tests (RT) and HIV nucleic acid amplification tests (NAAT). Related to these improvements is the possibility that alternative algorithms using combinations of currently approved HIV tests may function as well as if not better than the current algorithm, with more flexibility, improved accuracy, and lower cost. To this end, we evaluated the performance of 12 currently licensed tests and 1 in-house HIV test (6 EIA, 4 RT, and 3 NAAT) on panels of plasma samples from HIV-infected (n = 621 HIV type 1 [HIV-1] and 34 HIV-2) and uninfected (n = 513) people and of sequential specimens from people early in seroconversion (183 specimens from 15 patients). Test combinations were analyzed in two dual-test (sensitivity-optimized and specificity-optimized) algorithms and in a three-test (tie-breaking) algorithm, and performance was compared to the conventional algorithm. The results indicate that alternative algorithm strategies with currently licensed tests compare favorably with the conventional algorithm in detecting and confirming established HIV infection. Furthermore, there was a lower frequency of discordant or indeterminate results that require follow-up testing, and there was improved detection of early infection.

Genetic polymorphism in C8 beta-chains. Evidence for two unlinked genetic loci for the eighth component of human complement (C8).

Genetic polymorphism in the beta-subunit of the eighth component of human complement, C8, was defined by isoelectric focusing of serum in polyacrylamide gel in the presence of urea and development of specific patterns of hemolysis in an overlay gel containing antibody-sensitized erythrocytes and C8 beta-chain-deficient serum. Bands of hemolysis induced by serum from unrelated Caucasians suggested autosomal codominant inheritance of three structural alleles at a single locus, C82: C82 degrees A (acidic), C82 degrees B (basic), and C82 degrees A1 (very acidic) with frequencies of 0.952, 0.044, and 0.004, as well as the probable null allele C82 degrees Q0. The distribution of phenotypes agreed with the Hardy-Weinberg equilibrium. The previously described genetic polymorphism in human C8 defined with the use of "complete" C8 (C8 alpha-gamma-chain)-deficient serum was distinct from and independent of the inherited structural variation at C82. Therefore, the locus for C8 alpha-gamma-chains has been redesignated C81, and has the alleles C81 degrees A, C81 degrees A1, and C81 Q0. Linkage studies failed to show close linkage between the two loci for C8, C81, and C82, and between C82 and the major histocompatibility complex or C6.

Immunoregulatory subsets of the T helper and T suppressor cell populations in homosexual men with chronic unexplained lymphadenopathy.

Unexplained, generalized lymphadenopathy in homosexual men, which can be a prodrome to the acquired immunodeficiency syndrome, is associated with impaired cell-mediated immunity, a low ratio of T helper-inducer to T suppressor-cytotoxic cells (defined by the T4 and T8 monoclonal antibodies), and hypergammaglobulinemia. We performed double-marker studies on T cells by using a panel of monoclonal antibodies (Ia, T17, TQ1, and Leu-8), which reportedly detect activation or functional subsets of the T4 and T8 T cell populations. The T4:TQ1- or T4:Leu-8- subset, which is the major helper subset for B cell responses, is normally represented in lymphadenopathy patients. A depression in the reciprocal subset, T4:TQ1+ or T4:Leu-8+, accounts for the T4 T cell defect. Similarly, the TQ1 and Leu-8 markers delineate the abnormality of T8 T cells: the T8:TQ1- or T8:Leu-8- subset is elevated, whereas the T8:TQ1+ or T8:Leu-8+ subset is normally represented. We found no evidence of excessive activation of T4 T cells by using the T17 or Ia monoclonal antibodies. We did find an overall increase in Ia-positive T cells; however, this was due to increased T8:Ia+ cells. In functional studies, immunoglobulin production induced by pokeweed was subnormal. Most lymphadenopathy patients had normal T helper cell function when combined with normal B cells. The dampened pokeweed responses could be partially explained by depression of the T4:TQ1+ (or T4:Leu-8+) subset (which has minor help-associated function) and/or greater than expected suppression. However, subnormal pokeweed responses could not be totally explained by immunoregulatory T cell abnormalities because we also found an intrinsic defect in the B cell responses of lymphadenopathy patients.

Antibody response to human immunodeficiency virus in homosexual men. Relation of antibody specificity, titer, and isotype to clinical status, severity of immunodeficiency, and disease progression.

The titers and isotypes of antibodies to specific proteins of the human immunodeficiency virus were determined by Western blot analysis of sera from 107 homosexual men. Antibody titers were generally lower in sera from patients with the acquired immunodeficiency syndrome (AIDS) and in sera from men whose condition subsequently progressed to AIDS than in sera from men who had not progressed to AIDS. We found no evidence of isotypic prominence or restriction of the antibody response. In multivariate analysis, lower levels of CD4 helper cells were most highly associated with progression to AIDS. Lower antibody titers to the envelope protein gp110, the core protein p24, and the reverse transcriptase enzyme p51/65 were also predictive of progression to AIDS independent of their association with CD4 cell levels. These data suggest that differences in antibody levels are not simply a consequence of severe immunodeficiency but may be markers for control of infection.

Comparison of methods for assessing chemotaxis of monocytes and polymorphonuclear leukocytes isolated from patients with AIDS or AIDS-related conditions.

We evaluated the ability of normal human peripheral blood monocytes and polymorphonuclear leucocytes (PMNL) isolated from patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related conditions (ARC) to migrate toward a chemoattractant. Migration in blind-well chambers was compared to that under agarose. Chemotaxis results obtained from both assays for PMNL were similar, however there was a difference in the results for monocyte chemotaxis. PMNL isolated from patients with AIDS, but not ARC, exhibited decreased spontaneous and directed chemotaxis when assessed in blind-well chambers and under agarose. Spontaneous and directed chemotaxis in blind-well chambers of AIDS patients' monocytes was normal. Directed migration of monocytes from ARC patients was greater than that of control, but spontaneous migration was comparable. Under agarose, spontaneous migration was depressed in monocytes of AIDS patients, while migration toward the attractant was depressed in those of ARC patients.

Yersinia enterocolitica septicemia with septic arthritis.

We report a case of Yersinia enterocolitica septicemia with septic arthritis. Gentamicin administration controlled the septicemia but failed to eradicate the organisms in the joint, in spite of a synovial fluid level four times its minimal inhibitory concentration after four days of therapy. Development of azotemia necessitated change of antibiotic therapy to chloramphenicol, which eradicated the infection. While Y enterocolitica infection in the United States is uncommon, it must be added to the list of organisms causing suppurative arthritis and septicemia in susceptible hosts. Septic arthritis must be distinguished from the much more common reactive theumatic polyarthritis associated with Y enterocolimica infection, for which antibiotic therapy is neither needed nor helpful.

HIV-1 strains from a cohort of American subjects reveal the presence of a V2 region extension unique to slow progressors and non-progressors.

OBJECTIVES: To determine the molecular nature of HIV-1 quasispecies and their evolution, in vivo over time, in an American cohort of 22 homosexual men [four rapid progressors (RP), 15 slow progressors (SP) and three long-term non-progressors (LTNP)], infected with HIV-1 between 1982 and 1983, and to assess the possible role of the HIV-1 V2 region extension in HIV disease progression. DESIGN: Genetic and phylogenetic analyses of the V3 region and the nef gene clones over time from uncultured peripheral blood mononuclear cells (PBMC) of American patients with varying HIV disease progression rates. METHODS: Proviral DNA from longitudinally collected uncultured PBMC were subjected to PCR amplification in the nef gene and env V2 and V3 regions, followed by cloning, sequencing and phylogenetic analysis to establish evolutionary relationships between HIV-1 strains over time. RESULTS: Analysis of multiple viral clones showed nef gene deletions/insertions in 10 out of 15 SP, along with the coexistence of intact and defective nef gene lineages in the same individual over time, whereas these nefgene abnormalities were absent from HIV-1 strains from LTNP. Increasing quasispecies diversity in HIV-1 strains, over time, abrogation of a V3 region N-linked glycosylation site in > 60% of the clones, and, importantly, an extended V2 region were unique features of HIV-1 strains from SP and LTNP. CONCLUSIONS: The V2 region extension was unique to only SP and LTNP, and so may have a role in slow progression or non-progression of HIV disease. Increasing genetic diversity in HIV-1 strains in SP and LTNP correlated with the immunocompetent status of the host.

Adaptation to promiscuous usage of CC and CXC-chemokine coreceptors in vivo correlates with HIV-1 disease progression.

OBJECTIVE: To study coreceptor usage of sequential primary HIV-1 isolates in a longitudinal follow-up cohort of HIV-1-infected men to understand its contribution to pathogenesis of HIV disease. DESIGN: Viral coreceptor usage of sequential primary isolates from HIV-1-infected individuals was examined at various timepoints and data was compared with CD4 cell counts, rates of disease progression and beta-chemokine production. METHODS: Fifty-eight sequential primary isolates were obtained from four rapid progressors, six late progressors, and three long-term nonprogressors (LTNP) and their coreceptor usage was examined by infection of peripheral blood mononuclear cells (PBMC) from donors with wild-type or non-functional CC-chemokine receptor (CCR)-5, and by infection of GHOST4 cells expressing CD4 and various chemokine receptors [CCR-1-CCR-5, CXC-chemokine receptor (CXCR)-4, BOB/GPR15, BONZO/STRL33]. Production of RANTES and macrophage inflammatory protein (MIP)-1beta was examined using unstimulated or phytohemagglutinin (PHA)-stimulated PBMC isolated from these individuals at multiple timepoints during infection. RESULTS: A switch from single CCR-5 coreceptor usage to multiple coreceptor usage occurred in all four rapid progressors and three out of six late progressors. In addition to the commonly used coreceptors CXCR-4, CCR-5, and CCR-3, some of the viruses isolated from patients in the terminal stage of infection also used CCR-1, CCR-2b, CCR-4, and BOB as coreceptors. The emergence of viral variants capable of utilizing multiple coreceptors generally preceded CD4 cell decline to < 200 x 10(6)/l and correlated with the onset of AIDS. In contrast, three LTNP maintained exclusive usage of CCR-5 over a period of 7-12 years post-infection. Endogenous production of RANTES and MIP-1beta by PBMC from LTNP was not significantly different from rapid and late progressors. However, PHA-driven production of both chemokines was significantly higher in LTNP, suggesting that in vivo activating stimuli might curtail HIV replication by inducing these chemokines. CONCLUSIONS: Viral variants capable of utilizing a broad range of coreceptors correlated with HIV-1 disease progression. In contrast, LTNP maintain exclusive usage of CCR-5 and produce higher levels of beta-chemokines. Thus, both viral and host determinants leading to the emergence of viral variants capable of using an expanded range of coreceptors may be likely determinants of disease progression.

Development of AIDS, HIV seroconversion, and potential co-factors for T4 cell loss in a cohort of intravenous drug users.

A cohort of 334 intravenous (IV) drug users from New York City drug treatment programs were followed over a mean 9-month period. Among the 165 who were seropositive at enlistment, four developed clinical AIDS, for an annual rate of 3%. Elevated IgA was a significant predictor of developing AIDS. Among 72 subjects who were initially seronegative and who were re-interviewed, four were seropositive at follow-up, for a seroconversion rate of 7% per year among seronegatives. Among seropositive subjects who did not develop AIDS or fatal AIDS related complex (ARC), continued drug injection was associated with rate of T4 cell loss, and there was a non-significant trend for males to lose T4 cells more rapidly than females. While it was not possible to distinguish the mechanism underlying the relationship between continued drug injection and T4 cell loss, seropositive IV drug users should be warned that continued injection may lead to increased HIV-related immunosuppression as well as, if injection equipment is shared, risking viral transmission to others.

Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma.

OBJECTIVES: Kaposi's sarcoma-associated herpesvirus (KSHV), a newly discovered human gammaherpesvirus, is found in the majority of KS lesions from patients with and without AIDS. Peripheral blood mononuclear cells (PBMC) were examined for KSHV DNA to determine whether viral infection precedes onset of this neoplasm. DESIGN: Randomized and blinded case-control study of prospectively collected PBMC samples from ongoing cohort studies. METHODS: Paired PBMC drawn before and after KS onset from 21 AIDS-KS patients were compared to paired PBMC from 23 high-risk HIV-infected homo-/bisexual patients who did not develop KS and to a single PBMC sample from 19 low-risk, HIV-infected hemophiliac patients. Extracted DNA samples were amplified by polymerase chain reaction (PCR) using two non-overlapping nested primer sets to control for potential PCR contamination. RESULTS: In all comparisons, patients who went on to develop KS were significantly more likely to show evidence of KSHV infection prior to onset of KS than either control group. Of PBMC samples from AIDS-KS patients drawn prior to KS, 52% were positive for KSHV DNA whereas both high- and low-risk control groups had lower rates of PBMC infection (9-13%). KSHV infection can precede KS onset by up to 21 months among AIDS-KS patients. CONCLUSIONS: AIDS-KS patients are significantly more likely to show evidence of KSHV infection in PBMC prior to KS onset than control HIV-infected patients. Because identical PBMC samples from cases and controls were examined blindly, these results are not caused by a bias in tissue sampling. Homo-/bisexual and hemophiliac AIDS patients who do not develop KS appear to have a low prevalence of infection. These findings indicate that KSHV infection is specifically associated with the subsequent development of KS in AIDS patients.

Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group.

OBJECTIVE: To describe persons with HIV infection and AIDS but with persistently negative HIV antibody enzyme immunoassay (EIA) results. DESIGN: Surveillance for persons meeting a case definition for HIV-1-seronegative AIDS. SETTING: United States and Canada. PATIENTS: A total of eight patients with seronegative AIDS identified from July 1995 through September 1997. MAIN OUTCOME MEASURES: Clinical history of HIV disease, history of HIV test results, and CD4 cell counts from medical record review; results of testing with a panel of EIA for antibodies to HIV-1, and HIV-1 p24 antigen; and viral subtype. RESULTS: Negative HIV EIA results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA concentrations of 105,000-7,943,000 copies/ml. Using a panel of HIV EIA on sera from three patients, none of the HIV EIA detected infection with HIV-1, and signal-to-cut-off ratios were < or = 0.8 or all test kits evaluated. Sera from five patients showed weak reactivity in some HIV EIA, but were non-reactive in other HIV EIA. All patients were infected with HIV-1 subtype B. CONCLUSIONS: Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients with illnesses or CD4 cell counts suggestive of HIV infection, but for whom results of HIV EIA are negative, should consider p24 antigen, nucleic acid amplification, or viral culture testing to document the presence of HIV.

Ten-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome: evidence for continuing risk of developing AIDS.

Seventy-five homosexual men with lymphadenopathy syndrome (LAS), subsequently shown to be seropositive for the human immunodeficiency virus (HIV), were enrolled in a prospective study in Atlanta in 1982 and 1983. Subjects have been followed up at 3- to 6-month intervals with clinical and immunologic evaluations, including analysis of T-cell subsets. As of February 28, 1991, AIDS had developed in 36 (48%) of the 75 men. The AIDS cases continued to occur through the 10th year after onset of LAS; the 10-year cumulative incidence of AIDS was 56.6% (Kaplan-Meier survival analysis). Six-year incidence rates following the first observation of a T-helper cell count greater than or equal to 500/mm3, 400-499/mm3, 300-399/mm3, 200-299/mm3, and less than 200/mm3 were 29, 35, 50, 58, and 88%, respectively. Among individual symptoms and signs, only thrush conferred a poorer prognosis (odds ratio = 5.80; 95% confidence interval, 2.93, 11.39, p less than 0.001, Mantel-Byar analysis). The risk of AIDS persists 10 years after the onset of LAS. The AIDS incidence is related directly to T-helper cell depletion; with the exception of thrush, the presence or absence of symptoms and signs appears to be of lesser prognostic significance.

The search for human infection with simian type D retroviruses.

Evidence has recently been presented for an infection with a simian type D retrovirus in a patient with AIDS and lymphoma. We tested for simian type D infection in three groups of subjects: 375 patients with lymphoproliferative diseases (255 non-Hodgkin's, 88 Hodgkin's, and 32 chronic lymphoproliferative disease), of whom 75 were human immunodeficiency virus (HIV)-1 infected; seven persons with unexplained low CD4 lymphocyte counts with clinical conditions; and 45 blood donors, of whom 37 were human T-lymphocyte virus (HTLV)-I/II seroindeterminate and eight were HTLV-I/II and HIV-1 seronegative. Serum samples were screened for antibodies against simian type D retroviruses by an enzyme immunoassay, and reactive samples were analyzed by Western blotting. None of the samples were seropositive, but eight (five from non-Hodgkin's and three from Hodgkin's lymphoma patients) were seroindeterminate. Polymerase chain reaction analysis of genomic DNA from peripheral blood lymphocytes of all eight of these patients was carried out using simian type D gag generic primers with generic internal oligoprobing. All samples were negative. We conclude that simian type D infection is rare among HIV-infected and noninfected lymphoma patients, persons with unexplained low CD4 counts, and persons with HTLV-seroindeterminate test results.

Phase I study of intravenous gamma globulin in multiple myeloma.

Seventeen patients with multiple myeloma were given intravenous immunoglobulin at doses ranging from 150 mg/kg to 500 mg/kg in a phase I study. The intravenous immunoglobulin was well tolerated with only three transient episodes of mild clinical toxicity during 27 infusions. In no instance was hepatic or renal toxicity seen. Marked biologic variability over the one month study period in total IgG levels in patients with non-IgG myeloma and IgG subclasses in many of the patients was observed, making intravenous immunoglobulin half-life determinations based on IgG or IgG subclass levels problematical. The decay of functional antibody to hepatitis B surface antigen was determined. Analysis of the hepatitis antibody data suggested that intravenous immunoglobulin half-life was in the range of seven to 20 days for the entire study group and was not related to the isotype of the myeloma paraprotein or to the baseline levels of IgG. No infections were observed in the study group during the study period, but the potential for infection prophylaxis by intravenous immunoglobulin in myeloma patients must be evaluated in a randomized, prospective, controlled phase III study.

Serial determinations of HIV-1 titers in HIV-infected homosexual men: association of rising titers with CD4 T cell depletion and progression to AIDS.

Lymphocyte subset enumerations, antibody titers to specific proteins of human immunodeficiency virus (HIV), and measurement of infectious HIV titers in peripheral blood mononuclear cells were performed on serial blood specimens from 15 HIV-infected homosexual men with chronic lymphadenopathy syndrome (LAS); 6 of these men have subsequently progressed to AIDS (progressors), and 9 have remained clinically stable (nonprogressors). For the earliest samples studied, no test distinguished those who would progress to AIDS from those who have not. The two groups diverged significantly about 1 year before AIDS diagnosis in the progressor group. Virus titers rose in progressors but remained relatively stable in nonprogressors. CD4 T cells and the CD4 T cell subset, 4B4, declined more rapidly in progressors than in nonprogressors. HIV antibody titers tended to decline in progressors, but the differences were significant only for antibody and to the pol-encoded proteins, p51/65, and the gag-encoded polyprotein, p55. Before the onset of clinical AIDS, progressors are distinguished from nonprogressors by markedly different rates of CD4 cell depletion and virus replication, but the elements that control these dynamics remain to be defined.