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In the eastern Democratic Republic of the Congo, ongoing armed conflict increases the incidence of gender-based violence (GBV) and presents a distinct and major barrier to care delivery for all survivors of GBV. A specific challenge is providing emergency contraception, HIV prophylaxis and treatment for sexually transmitted infections to all survivors within 72 hours of violence. To address the multiple barriers to providing this time-sensitive medical care, Global Strategies and Panzi Hospital implemented the Prevention Pack Program. The Prevention Pack is a pre-packaged post-rape medical kit containing antiretroviral post-exposure prophylaxis, antibiotics for treatment of sexually transmitted infections and emergency contraception. The Prevention Pack Program combines community sensitisation about post-rape medical care with the provision of Prevention Packs and the implementation of a cloud-based and Global Positioning System (GPS)-enabled inventory management system. The Panzi Hospital gender-based violence team implemented the Prevention Pack Program at Panzi Hospital and 12 rural clinics in the South Kivu Province. The data manager took GPS coordinates of each site, provided an initial stock of Prevention Packs and then called all sites daily to determine demand for post-rape care and Prevention Pack consumption. Inventory data were entered into the GPS-enabled cloud-based inventory management system. Project personnel used the consumption rate, trends and geolocation of sites to guide Prevention Pack restocking strategy. Between 2013 and 2017, a total of 8206 individuals presented for care following rape at the study sites. Of the 1414 individuals who presented in the rural areas, 1211 (85.6%) did so within the first 72 hours of reported rape. Care was delivered continuously and without a single stockout of medication across all sites. The Prevention Pack Program provided timely and consistent access to emergency contraception, HIV prophylaxis and treatment for sexually transmitted infections for rape survivors in the eastern Democratic Republic of the Congo., Competing Interests: Competing interests: None declared.

We aimed to investigate the influence of class I and class II HLA specificities and of the concordance between maternal and infant HLA on vertical HIV-1 transmission. HLA typing of samples from mothers and infants enrolled in the Ariel study, a perinatal HIV-1 transmission cohort including 203 mother-infant pairs, was performed by serological and molecular methods. HLA effects were evaluated alone and by multivariate modeling considering also other known predictors of perinatal HIV-1 transmission (maternal viral load, antiretroviral therapy, duration of rupture of membranes, and histological chorioamnionitis). Modest associations were seen with specific HLA markers (increased risk with infant B67 and B58 and maternal DR1; decreased risk with maternal B12), but these were not statistically significant after adjusting for multiple comparisons. Mother-infant concordance at any class I locus was a strong predictor of transmission (odds ratio [OR], 4.16; p = 0.028). Transmission was not associated with class II concordance. Class I HLA concordance retained its importance after adjusting for maternal viral load, antiretroviral therapy, duration of rupture of membranes or histological chorioamnionitis. In multivariate modeling, only class I concordance (OR, 3.59; p = 0.069) and chorioamnionitis (OR, 3.79; p = 0.030) were retained as independent predictors of transmission. HLA alleles, and in particular the class I concordance between maternal and neonatal HLA, may regulate the risk of perinatal HIV-1 transmission.

Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-1-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control.

Most HIV-1 infections of children result from mother-to-infant transmission, which may occur perinatally or postnatally, as a consequence of breast feeding. In this study, the influence of maternal viral load on transmission of infection to infants from non-breast-feeding mothers was examined using samples of plasma and peripheral blood mononuclear cells (PBMCs) collected at several time points during pregnancy and the 6-month period after delivery. These samples were analyzed by several quantitative methods, including virus cultures of PBMCs and polymerase chain reaction (PCR) assays for HIV-1 RNA in plasma and DNA in PBMCs. The risk of transmission increased slightly with a higher viral load, but transmission and nontransmission occurred over the entire range of values for each assay. No threshold value of virus load was identified which discriminated between transmitters and nontransmitters. We also noted a significant rise in viral load and a decline in CD4+ lymphocytes in the six months after delivery. These findings suggest that a high maternal viral load is insufficient to fully explain vertical transmission of HIV-1. Additional studies are needed to examine the post-partum increase in viremia.

Objective: To identify the population of human immunodeficiency virus-infected pediatric long- term survivors (LTS) followed in major medical institutions in California, Florida and New Jersey., Methods: A cross-sectional survey was performed with data collection forms sent to all investigators. Demographic, clinical, and laboratory data were obtained on all living patients >/=8 years infected in the perinatal period with human immunodeficiency virus., Results: A total of 143 perinatally infected and 54 children infected by neonatal transfusion were identified. Fifty-four children (27%) had absolute CD4 counts >/=500 cells/mm (group 1: mean age 9.8 years), 54 children (27%) had CD4 counts between 200 and 500 cells/mm (group 2: mean age 10.1 years), and 89 children (45%) had CD4 counts <200 cells/mm (group 3: mean age 10.4 years). Ninety-five (48%) patients had developed AIDS defining conditions; 14 (26%) in group 1, 26 (48%) in group 2, and 55 (62%) in group 3. Ninety-two percent of patients had received antiretrovirals. Perinatally human immunodeficiency virus-infected children tended to be younger (mean age 9.8 years) than children infected via a blood transfusion (mean age 11 years). Generalized lymphadenopathy was the most prevalent clinical finding. Lymphoid interstitial pneumonia and recurrent bacterial infections were the most prevalent acquired immune deficiency syndrome-defining conditions. Twenty percent of LTS had CD4 counts >/=500 cells/mm and no immune deficiency syndrome-defining conditions., Conclusions: Pediatric LTS were in variable stages of disease progression. The proportion of children within each CD4 strata did not differ by mode of acquisition of infection. Increased CD4 counts were inversely proportional to age. Only 20% of pediatric LTS had minimal to no disease progression.

To assess the safety, pharmacokinetics, and antiviral effects of intravenous recombinant CD4 immunoglobulin G (CD4-IgG), a 12-week Phase One study with an optional maintenance phase was performed. Twenty-two subjects with advanced human immunodeficiency virus (HIV) infection were enrolled; 15 subjects completed the initial 12 weeks. CD4-IgG doses were 30, 100, or 300 micrograms/kg weekly; 1,000 micrograms/kg once, twice, or three times per week; or 3,000 micrograms/kg twice weekly. Serum concentrations of CD4-IgG increased linearly with dose, with average peak serum concentrations of 22 micrograms/ml with 1,000 micrograms/kg. CD4-IgG was well tolerated; one patient had self-limited tachycardia and flushing associated with CD4-IgG therapy. No changes were seen in CD4 cell counts, hematologic or coagulation studies, serum chemistries, HIV p24 antigen titers, or plasma HIV titers. No subject developed anti-CD4 antibodies. HIV isolates from five patients had IC90 values that were higher than the peak concentrations of CD4-IgG achieved in those patients. Additional studies that achieve higher CD4-IgG concentrations are necessary to evaluate the antiviral activity of this compound.

Recombinant CD4-immunoglobulin G (rCD4-IgG) is a 98-kDa human immunoglobulin-like protein that is produced by fusing the gp120 binding domain of CD4 to the Fc portion of the human IgG1 heavy chain. This hybrid molecule was given to human immunodeficiency virus (HIV)-infected pregnant women at the onset of labor by intravenous bolus at 1 mg/kg of body weight (group A; n = 3) and 1 week prior to and at the onset of labor by the same route and at the same dose (group B; n = 3). In addition to pharmacokinetic studies, safety in the mothers and infants was determined through routine chemistries, hematology, and urinalysis; immunologic and HIV infection statuses in the infants were assessed through lymphocyte cultures, p24 antigen level determination, culture of HIV from plasma, PCR, lymphocyte subset enumeration, quantitative immunoglobulin analysis, and lymphocyte proliferation. Thirty minutes after the rCD4-IgG injection, concentrations in maternal serum were 12 to 23 micrograms/ml. These concentrations declined slowly, with initial and terminal half-lives (mean +/- standard deviation) of 9.95 +/- 3.23 and 47.6 +/- 22.3 h, respectively. Infants were born 2.6 to 46.5 h after rCD4-IgG administration; concentrations of rCD4-IgG in cord blood ranged from 28 to 107 ng/ml. The half-life of rCD4-IgG in infants ranged from 5 to 29 h. These data demonstrate that the transfer of rCD4-IgG from the mother to the fetus is rapid and that newborns do not appear to have any difficulty eliminating rCD4-IgG. No safety concerns in mothers or infants were encountered. Although the study did not address the question of efficacy, none of the infants was HIV type 1 infected 36 months later. In summary, these findings document that bifunctional immune molecules can be transported across the placenta, and this general approach may be used in the future to block vertical transmission of HIV type 1.

The next decade of HIV/AIDS must resolve critical issues. It will be necessary to probe deeply to examine what is currently known, identify what needs to be known, and find ways to solve the issues that must be confronted. How to best achieve solutions in a timely manner must also be determined. Seven priorities of major importance have been identified. There are others, and there will be new ones. Each issue is complex, but each one must be faced with the hope that solutions will be found. After 10 years, HIV infection is at risk of becoming institutionalized, bringing with it an acceptance of the issues as inherent to the disease. Patients look to the medical profession and scientific community to provide hope. But there are also significant educational, psychological, social, and public health issues that must be resolved. The first decade of AIDS consisted of recognition, diagnosis, and early treatment. If hope is to be brought to our children and their parents, the next decade must consist of the prevention and therapeutic control of HIV and its complications.

We hypothesize that graft-versus-host disease (GVHD) does not occur in HIV-1-infected subjects because graft cells (or host cells recognizing antigenic differences in other host cells) mediating the graft-versus-host reaction are CD4+ T cells that become infected with HIV-1 and are rendered immunologically incompetent. GVHD has been documented in all forms of genetic or acquired severe T-cell deficiencies, except in patients with AIDS. Its striking absence in multiply transfused patients suggests that HIV-1 infection prevents its occurrence. We propose the following sequence of events. Transfusion of immunocompetent cells into HIV-1-infected subjects results in an in vivo allogeneic cell response. The activated CD4+ T cells become infected with HIV-1 and are rendered immunologically incompetent or are destroyed and cannot, therefore, initiate GVHD. Suggestions have been made by others that a GVHD-like mechanism results from HIV-1 infection and is a potentially important factor in the pathogenesis of AIDS and that, therefore, immunosuppressive therapy should be evaluated in HIV-infected patients. However, since most immunosuppressive therapy cannot be targeted to a specific functional immune cell, and since enhancement of immunity is more likely to prevent many of the complications of HIV-1 infection that ultimately cause death, treatment of HIV-1-infected patients should be directed toward improving immune function rather than immunosuppression.

Ten patients with AIDS were enrolled in a phase I/II protocol of recombinant CD4-IgG (rCD4-IgG) treatment. Patients' peripheral blood leukocytes (PBL) were tested before, during, and after therapy with rCD4-IgG for T helper (TH) cell function assessed by antigen- and mitogen-stimulated proliferation and interleukin-2 production in response to influenza A virus, allogeneic PBL (alloantigens), and phytohemagglutinin. Although clinical benefit was not evident, rCD4-IgG treatment was associated with rapid and potent improved TH cell function for two of three stimuli tested in 90% of the patients. These data are complemented by an in vitro experimental model that demonstrates the opposing immunologic effects of rgp120 and rCD4-IgG on TH cell function of PBL from uninfected individuals. Thus, restoration of TH cell function by rCD4-IgG in the absence of increased CD4 cell counts could be due to removal of an immunosuppressive factor, possibly gp120. These findings suggest that rCD4-IgG can induce partial restoration of immune function in AIDS patients, even in the absence of apparent short-term clinical benefit.

A novel implantable device, the analytic bone implant, was used in order to establish a model for studies of bone-healing and the evaluation of factors that augment the process, such as transforming growth-factor beta (TGF-beta). This device was implanted into the tibiae of four baboons. After healing, bone was removed from the center chamber. Recombinant human TGF beta-1 was then delivered to the core of the device. After twenty-two days of healing, the device was disassembled and the newly formed bone was removed from the core of the implant for histomorphometric analysis. An analysis of the bone revealed a substantial effect of TGF-beta on osteoblastic activity and proliferation compared with that seen in control and placebo groups. However, despite increased osteoblastic activity, trabecular bone volumes at twenty-two days were equivalent among the groups. The number of osteoclasts and the erosion of the surface were also increased, although not significantly so. Substantial endochondral formation of bone was seen in the supraperiosteal tissues directly over the implants that contained TGF-beta but not over the implants in the control and placebo groups. These data demonstrate the utility of this bone-implant model for studies of bone-healing with minimally invasive methods. In addition, use of the device provided the first in vivo data on the effects of TGF-beta at an intermediate (twenty-two-day) time-point in the healing process in a non-human primate.

The effects of recombinant human transforming growth factor beta 1 (rhTGF-beta 1) on wound healing were examined in a rabbit ear ulcer model in which rhTGF-beta 1 was applied to full-thickness biopsy ulcers on the ears. The influence of perichondrium on healing was studied by comparing ulcers with and without perichondrium on 1) formation of total healing wound area (HWA, the newly formed connective and granulation tissues within the ulcer) over time and 2) the amount of collagen synthesized by the wound tissue at day 5. The HWA of ulcers with intact perichondrium increased sharply with time and reached a plateau at day 7, whereas a slower healing occurred in the perichondrium-free model where maximal HWA appeared at day 14. Topical application of 100 ng of rhTGF-beta 1 per wound accelerated healing by increasing HWA in both models. The enhancement of healing by rhTGF-beta 1 was associated with increased collagen synthesis. The percent collagen synthesis in the rhTGF-beta 1 was doubled in the perichondrium-intact ulcers and increased 40% in the perichondrium-free ulcers. DNA synthesis in the perichondrium-intact ulcers was not altered by rhTGF-beta 1 when measured at day 5 by in vitro labeling with [3H]thymidine ([3H]TdR). Autoradiography indicated that the primary cells labeled in the wound tissue were epithelial cells and rhTGF-beta 1 enhanced the migration of these cells from the wound margin towards the center. To evaluate the effects of rhTGF-beta 1 on fibroblasts derived from the granulation tissue of the wound, cells were treated with increasing concentrations of rhTGF-beta 1 and DNA and collagen synthesis were determined. rhTGF-beta 1 elicited a biphasic change in percent collagen synthesis with a maximal increase of 50% at 20 pM followed by a decline. A twofold increase in [3H]TdR incorporation that plateaued at 1 nM was also observed. Our results indicate that the cellular responses to rhTGF-beta 1 differ in vivo and in vitro. The perichondrium-intact ulcers contain more wound tissue and have larger responses to rhTGF-beta 1 stimulation, which allows better examination of biochemical and cellular events. The in vivo mechanisms are multi-factorial, which may involve cell migration and recruitment as results of numerous cell/cell and cell/matrix interactions.

A single application of recombinant human transforming growth factor beta 1 (rhTGF-beta 1) adjacent to cartilage was found to induce bone formation in rabbit ear full-thickness skin wounds. At doses that optimally promote soft tissue healing, 25-100 ng rhTGF-beta 1 per wound caused osseous tissue formation starting 21 days after wounding to reach a peak incidence and area of bone formation at day 42. Bone formation was followed by active remodeling, resulting in lower incidence and area of bone formation at days 56 and 70. The early phase of bone formation was located overlying the cartilage and involved perichondrial cells that appeared to differentiate directly into osteoblasts forming bone matrix without a cartilage precursor. Cartilage was replaced with bone at later time points. rhTGF-beta 1 was able to increase the ratio of osteoblasts to osteoclasts lining the trabecular surface of bone and thus increase the net amount of bone formation. The present studies suggest a potential therapeutic role for rhTGF-beta 1 in hard tissue repair.

We examined the effects of interferon-gamma (IFN-gamma) on development of the surfactant system in alveolar epithelial cells of fetal lung. Explants of second-trimester human fetal lung were cultured for 1 to 6 days in serum-free medium containing recombinant human IFN-gamma (0.03 to 30 ng/ml) and/or dexamethasone (10 or 100 nM). Treatment for 3 days with IFN-gamma alone, dexamethasone alone, and IFN plus dexamethasone increased the content of surfactant protein A (SP-A, 28 to 36 kD) by approximately 3-, 2.5-, and 10-fold, respectively. The biphasic response pattern of SP-A to dexamethasone (stimulation initially and inhibition with continued culture) was not altered by the presence of IFN-gamma. IFN-gamma also stimulated accumulation of SP-A mRNA (2.7-fold at 24 h) but did not affect the levels of mRNAs for surfactant protein B (18 kD) and surfactant protein C (5 kD). To assess the effect of IFN-gamma on synthesis of surfactant lipids, we determined the content of phosphatidylcholine, the rate of labeled choline incorporation into phosphatidylcholine, saturation of newly synthesized phosphatidylcholine, and the activity of fatty acid synthetase, a glucocorticoid-inducible enzyme. Treatment of explants for 5 days with IFN-gamma had no effect on these parameters. Studies by light and electron microscopy revealed little difference between control and IFN-treated explants with regard to cell viability and epithelial cell differentiation. We conclude that IFN-gamma has a selective stimulatory effect on SP-A among surfactant components.(ABSTRACT TRUNCATED AT 250 WORDS)

A new animal model to study secondary intention wound healing and the effects of topically applied rhTGF-beta 1 was developed. A time course study was performed of full thickness 6 mm punch wounds placed on the backs of anesthetized pigs and treated once with either 3% methylcellulose or rhTGF-beta 1 in 3% methylcellulose or left untreated. Wounds receiving rhTGF-beta 1 had enhanced tensile strength at days 4 and 7 compared to controls. Studies of the response on days 4 and 7 to graded doses of rhTGF-beta 1 showed that a dose of 250 or 2500 ng rhTGF-beta 1 gave a similar enhanced wound strength, while 25 ng rhTGF-beta 1 had no effect. Blood flow to treated granulating wounds as measured by 141Ce microspheres indicate an increase in flow in wounds treated with 250, 500 or 2500 ng rhTGF-beta 1 compared to controls. These results indicate a possible use for rhTGF-beta 1 in enhancing wound healing clinically.

A dermal ulcer wound-healing model was established in rabbit ear to examine the effects of recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) in wound healing. Histomorphometric examination of the wounds indicate a biphasic healing response 7 days after a single application of rhTGF-beta 1 at the time of wounding. Statistically significant healing occurred at 5-100 ng but not at higher doses of 500 or 1000 ng rhTGF-beta 1/wound. Enhanced collagen synthesis as determined by [3H]proline incorporation occurred at 15 and 25 ng and was significantly depressed at 500 ng rhTGF-beta 1/wound. Multiple doses of 100 ng rhTGF-beta 1 applied to the wound at the time of wounding and for 3 days after wounding provided results comparable to the single application of growth factor. Delaying treatment 24 hr after wounding did not enhance wound healing compared with vehicle. Our findings suggest that rhTGF-beta 1 can be a valuable growth factor to improve the healing of ulcer wounds.

Previous studies have demonstrated that TGF-beta possesses many of the biologic properties necessary for acceleration of the normal wound healing process. We report that recombinant human TGF-beta 2 (rhuTGF-beta 1) increases wound strength and accelerates wound closure when applied topically to experimental wounds. Doses of 5 to 1,000 ng/wound increased wound strength in a dose-response manner and wound strength increase as high as 161% above control in the rat incisional wound model. Increased wound strength was observed as early as 3 days following rhuTGF-beta 1 application and continued to Day 28. In the rabbit ear ulcer model, acceleration of wound closure was observed following doses of 5 to 100 ng/wound applied a single topical application. No adverse effects of rhuTGF-beta 1 were observed. The amount of fibrous tissue, scar formation, and mitotic figures were not significantly greater than control. Epithelialization of rhuTGF-beta 1-treated wounds was not impeded. rhuTGF-beta 1 induced bone formation in the rabbit ear ulcer model but not in the rat incisional model, suggesting that precursor cells, such as perichondrial cells, are required for the bone forming activities of TGF-beta 1.

To assess safety and efficacy of high-dose intravenous immunoglobulin therapy in patients with primary immunodeficiency syndromes we treated a group of 19 patients with a monthly dose of 400 mg/kg of reduced and alkylated, maltose-containing immunoglobulin (Gamimune, Cutter Biological, Berkeley, California) and compared their responses with a group of 16 patients receiving 100 mg/kg per month intravenously. Side effects observed were mild to moderately severe and similar in both groups. In one adult patient receiving the high dose a severe enough reaction developed during the first infusion to exclude her from the study. Serum IgG levels of patients receiving high-dose immunoglobulin showed a stepwise increase in both trough and peak values until a new plateau was reached after four to six infusions. None of the patients receiving the low dose showed such a stepwise increase. On average, serum IgG levels rose by approximately 250 mg/dl for each 100 mg/kg immunoglobulin infused. The mean catabolic rate of the infused IgG was estimated to be 26 days in patients receiving high-dose immunoglobulin infusions. We demonstrated that 400 mg/kg immunoglobulin given intravenously every four weeks to patients with immunodeficiency results in a substantial increase in serum IgG during the postinfusion period, suggesting persistence of specific antibody throughout the interval between infusions.

The acquired immunodeficiency syndrome has been observed with increasing frequency in children with associated hemophilia, high-risk environmental backgrounds, and blood transfusions. AIDS should be considered in the differential diagnosis of childhood immunodeficiency, and it must be distinguished from congenital disorders. We emphasize the importance of epidemiologic, clinical, and laboratory data in diagnosis and aggressive management of infectious complications. The relationship between human retrovirus infection and AIDS remains to be precisely defined, especially with regard to cofactors that may play a role in the development of severe immunodeficiency following exposure to the agent.

A 5-year-old girl with a history of recurrent infection and anaemia has no measurable purine nucleoside phosphorylase (N.P.) activity in her red blood-cells. Her serum-immunoglobulin levels are normal, as are her antibody responses to thymus dependent and independent antigens. However, she has severe lymphopenia, pronounced depression of lymphocyte response to mitogenic and allogeneic cell stimuli, and greatly decreased T-cell rosette formation. Her parents are second cousins; their red cells contain less than half the normal level of N.P. activity. They also share an unusual N.P. isozyme pattern indicative of molecular hybridisation between catalytically active and inactive subunits, which strongly supports the assumption that they are heterozygous and their daughter is homozygous for a "silent" allele at the N.P. gene locus. Inherited deficiency of adenosine deaminase, an enzyme catalysing a reaction only one metabolic step away from that of N.P., is known to cause immunodeficiency. It is therefore very likely that this patient's lack of demonstrable N.P. activity is responsible for her syndrome.

We evaluated the effects of recombinant interleukin 2 (IL-2) on the proliferative responses to mitogens of peripheral blood mononuclear cells (PBMC) from three adenosine deaminase (ADA)-deficient patients. There was significant enhancement by IL-2 of the proliferative responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) of PBMC from all three patients. We found that normal PBMC respond with increased numbers of CD3-positive cells when exposed to PHA or PWM and that the response by normal CD8-positive cells was greater than that by CD4-positive cells. In contrast, we found that in ADA-deficient cells the response is almost entirely due to the CD3/CD4-positive population of lymphocytes. These results could not be explained by either the culture conditions or the possibility of a mixed chimeric state. When we evaluated an in vitro cell model of ADA deficiency using an ADA inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), we found that the inhibitory effect of EHNA plus deoxyadenosine on mitogen-stimulated PBMC could not be prevented by IL-2. These results suggest that the immunodeficiency in ADA deficiency includes the absence or failure of a subset of T cells to make IL-2 and the failure of the CD8-positive subset to respond to IL-2. Also, the in vitro cell model of ADA deficiency using EHNA as the ADA inhibitor is limited in its use in understanding the pathogenesis of this disease.

To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P less than 0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection.

T-helper:T-suppressor cell ratios of 1 or less were found in 2 of 42 homosexual men without antibodies to cytomegalovirus but in 33 of 67 homosexual men with antibodies (p less than 0.001). Of 34 men without antibody who were followed prospectively, 12 became seropositive for cytomegalovirus and all 12 developed helper: suppressor ratios of less than 1.0. These ratios remained at 1 or less for an average of 9.6 months but persisted for 15 months or more in 3 men. None of the men in the prospective study developed antibodies to the acquired-immunodeficiency-syndrome-associated retrovirus. These results indicate that in the homosexual men studied, abnormally low T-lymphocyte helper: suppressor ratios occurred almost exclusively in those who were infected with cytomegalovirus, and in those prospectively followed low ratios did not reflect contact with the syndrome-associated retrovirus. Abnormal ratios were rarely seen in men who had never been exposed to cytomegalovirus. Thus, cytomegalovirus infection may be an important cofactor in the immunologic disorders leading to the acquired immunodeficiency syndrome.