Asymptomatic HIV-infected Persons Research Articles

Seronegative Infection with Toxoplasma gondii in Asymptomatic Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Patients and in Blood Donors.

Background: Toxoplasmosis is a common opportunistic infection in AIDS patients. The routine diagnostics is based on serologic testing and IgG avidity index, but it may have limited utility in immunodeficient patients; thus, it is recommendable to detect T. gondii DNA in subjects with advanced HIV disease. The results of the studies published so far focused on patients with clinical symptoms of toxoplasmosis. Our study encompassed a group of HIV-infected subjects on cART therapy, without immunological disturbances and clinical symptoms of T. gondii infection. Methods: The study was retrospective, and samples were collected between 2013 and 2016. We evaluate the prevalence of serological (IgM, IgG, and avidity IgG) and molecular (DNA) T. gondii infection markers in asymptomatic HIV-infected patients and the control group using serologic (ELISA) and quantitative (real-time PCR) molecular testing. Results: Of 152 HIV-infected in routine follow-up tested for T. gondii IgM and IgG, 6 (3.9%) and 50 (32.9%) were positive, respectively. Of 168 serum samples from blood donors, 1 (0.6%) and 49 (29.2%) were IgM+ and IgG+ positive, respectively. IgM seroprevalence in HIV-infected patients was significantly higher than in blood donors. T. gondii DNA (genotype II) was identified in 47 (30.9%) HIV-infected patients, with 13 (8.6%) IgM−IgG− samples. In blood donors, T. gondii DNA was present in 15 (8.9%) IgM−IgG−. Conclusions: In both groups, T. gondii DNA was detectable in seronegative subjects, implying the need to supplement the routine serological testing via the molecular method. It can help the accurate monitoring of the reactivation of infection in asymptomatic HIV-infected persons, and the quick introduction of specific therapy, in blood donors, would be of high importance for safe blood donations.

LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY.

SUMMARYAIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcus species. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.

Diversity and antifungal resistance patterns of prevalent opportunistic pathogenic yeasts colonizing the oral cavities of asymptomatic human immunodeficiency virus-infected individuals, and their relation to CD4(+) counts.

Yeasts are important opportunistic pathogens, in individuals infected with human immunodeficiency virus (HIV). Yeast species inhabiting the oral mucosa of HIV-infected persons can act as source of oral lesions, especially as the individual progresses towards immunocompromised state. Present study was conducted to evaluate the diversity of yeasts in oral cavities of asymptomatic HIV-infected persons and their association with CD4(+) cell counts. 100 HIV seropositive subjects and 100 healthy controls were screened for oral yeast carriage using standard procedures. Of the 100 HIV-seropositive persons screened, 48 were colonized by different yeasts, either alone or in association with another species. Candida albicans was the most common species (56.90%) while non C. albicans Candida (NCAC) accounted for 39.65%. Among NCAC, Candida tropicalis and Candida krusei were most common. One isolate each of rare opportunistic pathogenic yeasts, Geotrichum candidum and Saccharomyces cereviseae, was recovered. The control group had an oral candidal carriage rate of 23%; C. albicans was the predominant species, followed by Candida glabrata, C. tropicalis and Candida parapsilosis. Antifungal susceptibility testing revealed no resistance in C. albicans, to the commonly used antifungal agents, whereas resistance or dose dependent susceptibility to fluconazole was observed in some of the NCAC species. Oral carriage of opportunistic pathogenic yeasts was greater in HIV-seropositive persons heading towards immunocompromised state, as evidenced by their CD4(+) cell count. The predominant yeast isolated in this study (C. albicans), was found to be susceptible to commonly used antifungals.

Diversity and antifungal resistance patterns of prevalent opportunistic pathogenic yeasts colonizing the oral cavities of asymptomatic human immunodeficiency virus-infected individuals, and their relation to CD4+ counts

Background:Yeasts are important opportunistic pathogens, in individuals infected with human immunodeficiency virus (HIV). Yeast species inhabiting the oral mucosa of HIV-infected persons can act as source of oral lesions, especially as the individual progresses towards immunocompromised state. Present study was conducted to evaluate the diversity of yeasts in oral cavities of asymptomatic HIV-infected persons and their association with CD4+ cell counts.Materials and Methods:100 HIV seropositive subjects and 100 healthy controls were screened for oral yeast carriage using standard procedures.Results:Of the 100 HIV-seropositive persons screened, 48 were colonized by different yeasts, either alone or in association with another species. Candida albicans was the most common species (56.90%) while non C. albicans Candida (NCAC) accounted for 39.65%. Among NCAC, Candida tropicalis and Candida krusei were most common. One isolate each of rare opportunistic pathogenic yeasts, Geotrichum candidum and Saccharomyces cereviseae, was recovered. The control group had an oral candidal carriage rate of 23%; C. albicans was the predominant species, followed by Candida glabrata, C. tropicalis and Candida parapsilosis. Antifungal susceptibility testing revealed no resistance in C. albicans, to the commonly used antifungal agents, whereas resistance or dose dependent susceptibility to fluconazole was observed in some of the NCAC species.Conclusion:Oral carriage of opportunistic pathogenic yeasts was greater in HIV-seropositive persons heading towards immunocompromised state, as evidenced by their CD4+ cell count. The predominant yeast isolated in this study (C. albicans), was found to be susceptible to commonly used antifungals.

Study on quality of life of asymptomatic HIV infected persons with traditional Chinese medicine

Study on quality of life of asymptomatic HIV infected persons with traditional Chinese medical, which can provide the clinical basis for improving the quality of life. This study applied a randomized, double-blind, and placeb-parallel control designed method to select 1 200 persons in the asymptomatic period of HIV infection as the subjects. The subjects were randomly divided into the treatment group and the control group at the ratio of about 2:1. According to the results of monthly differential diagnosis of TCM, the test group and the control group were given homologue Chinese drugs preparations and model Chinese drugs. The total study period was 18 months. Using PRO scale and the world health organization AIDS determination of quality of life short scale form (WHOQOL-HIV-BREF) to investigate asymptomatic HIV infected persons, according to different times, we calculated the total score and each domain score of quality of life of the treatment group and control group, we did statistical analysis. Form the PRO scale,we can see that the treatment group showed a trend of stability, compared with the control group with significant statistical difference (P < 0.05) after 6 months; from the WHOQOL-HIV scale analysis, we can see that compared with before treatment, the quality of life of the treatment group was increased, the difference was significant (P < 0.05), but the quality of life of the control quality of life was decreased, the differences was significant (P < 0.05). Dialectical therapy of Chinese medicine can significantly improve the patient's quality of life, which can provide the basis for the prevention and control policy formulation and implementation with asymptomatic HIV infected persons.

When to start antiretroviral therapy: the need for an evidence base during early HIV infection

BackgroundStrategies for use of antiretroviral therapy (ART) have traditionally focused on providing treatment to persons who stand to benefit immediately from initiating the therapy. There is global consensus that any HIV+ person with CD4 counts less than 350 cells/μl should initiate ART. However, it remains controversial whether ART is indicated in asymptomatic HIV-infected persons with CD4 counts above 350 cells/μl, or whether it is more advisable to defer initiation until the CD4 count has dropped to 350 cells/μl. The question of when the best time is to initiate ART during early HIV infection has always been vigorously debated. The lack of an evidence base from randomized trials, in conjunction with varying degrees of therapeutic aggressiveness and optimism tempered by the risks of drug resistance and side effects, has resulted in divided expert opinion and inconsistencies among treatment guidelines.DiscussionOn the basis of recent data showing that early ART initiation reduces heterosexual HIV transmission, some countries are considering adopting a strategy of universal treatment of all HIV+ persons irrespective of their CD4 count and whether ART is of benefit to the individual or not, in order to reduce onward HIV transmission. Since ART has been found to be associated with both short-term and long-term toxicity, defining the benefit:risk ratio is the critical missing link in the discussion on earlier use of ART. For early ART initiation to be justified, this ratio must favor benefit over risk. An unfavorable ratio would argue against using early ART.SummaryThere is currently no evidence from randomized controlled trials to suggest that a strategy of initiating ART when the CD4 count is above 350 cells/μl (versus deferring initiation to around 350 cells/μl) results in benefit to the HIV+ person and data from observational studies are inconsistent. Large, clinical endpoint-driven randomized studies to determine the individual health benefits versus risks of earlier ART initiation are sorely needed.The counter-argument to this debate topic can be freely accessed here: http://www.biomedcentral.com/1741-7015/11/147.

Invasive Amebiasis as an Emerging Parasitic Disease in Patients With Human Immunodeficiency Virus Type 1 Infection in Taiwan

Whether risk of invasive amebiasis due to Entamoeba histolytica is higher among human immunodeficiency virus (HIV)-infected persons than uninfected persons remains unclear, although intestinal colonization by Entamoeba dispar is common among men who have sex with men. Our objective was to determine the prevalence of invasive amebiasis and intestinal colonization by E histolytica and E dispar in HIV-infected persons and uninfected controls. We assessed the prevalence of invasive amebiasis by case review of 951 HIV-infected persons and by serologic studies of 634 of the 951 HIV-infected persons, 429 uninfected controls with gastrointestinal symptoms, and 178 uninfected healthy controls using indirect hemagglutination antibody assay. We assessed the rate of intestinal colonization by E histolytica and E dispar by fecal antigen and polymerase chain reaction tests in 332 asymptomatic HIV-infected persons and 144 of the 178 uninfected healthy controls. Forty-nine (5.2%) of 951 HIV-infected persons had 51 episodes of invasive amebiasis. A high indirect hemagglutination antibody titer was detected in 39 (6.2%) of 634 HIV-infected persons compared with 10 (2.3%) of 429 uninfected controls with gastrointestinal symptoms and 0 of 178 uninfected healthy controls (P<.001). Stool specimens from 40 (12.1%) of 332 HIV-infected persons and 2 (1.4%) of 144 uninfected healthy controls were positive for E histolytica or E dispar antigen (P<.001). Ten (25.0%) of the 40 antigen-positive stool specimens from HIV-infected persons contained E histolytica. Persons infected with HIV in Taiwan are at increased risk for invasive amebiasis and exhibit a relatively high frequency of elevated antibody titers and intestinal colonization with E histolytica.

Are there predictors for sexual risk behavior in HIV-infected patients?

The influence of four coping strategies ("rumination," "search for affiliation," "threat minimization," and "search for information"), four social network dimensions ("affectively positive," "affectively negative," "accepting confidants," and "liking confidants") and sociodemographics on the sexual risk behavior of HIV-infected persons were analyzed in sexual encounters with steady and casual partners. The analysis examines bi- and multivariately the predictors for sexual risk behavior. The study population consisted of 103 asymptomatic HIV-infected persons (80 men, 23 women, mean age 34 years, range 21-69 years) who participated in our prospective study and reported their sexual contacts during the previous 6 months. In sexual encounters with steady partners, the risk of unprotected behavior increased with the frequency of sexual contact. In these encounters, coping strategies and social network had no influence on sexual risk behavior. In sexual contacts with casual partners, the number of contacts with these partners was also of importance. The coping strategy "rumination" correlates significantly with enhanced risk behavior. In sexual contacts with casual partners, there was no correlation between sexual risk behavior and the three other coping strategies or social network. In multivariate analysis, the number of sexual contacts was the only significant predictor for sexual risk behavior with steady partners as well as casual ones. As sexual activity with HIV-infected persons is not absolutely safe, further prevention campaigns have to focus more on the motivation for safe sex, its situational aspects, and partners' responsibility.

HIV-1 alters T helper cytokines, interleukin-12 and interleukin-18 responses to the protozoan parasite Leishmania donovani.

To investigate the in vitro and in vivo effect of HIV-1 on lymphoproliferative and T helper (Th) cytokine responses in leishmaniasis. Th1 [interleukin (IL)-2 and interferon (IFN)-gamma] and Th2 (IL-4 and IL-10) as well as IFN-gamma-inducing cytokines (IL-12 and IL-18) were measured in antigen and mitogen-stimulated culture supernatants of peripheral blood mononuclear cells (PBMC) of healthy donors, HIV-infected and visceral leishmaniasis (VL) patients with or without HIV co-infection. Proliferative responses to phytohaemagglutinin (PHA) were significantly lower in PBMC from VL and asymptomatic HIV-infected persons compared with responses in healthy individuals. VL-HIV co-infected patients showed the lowest responses. Although there was no significant difference in the Leishmania-induced proliferative responses among the healthy group and those infected with HIV only, VL patients (with or without HIV) exhibited very low proliferation. When cultured with PHA or Leishmania, PBMC from healthy donors produced high levels of a Th1 cytokine (IFN-gamma) and low levels of Th2 cytokines (IL-4 and IL-10). In addition, co-culturing PBMC from healthy donors with a killed HIV preparation abrogated the production of IFN-gamma induced by Leishmania and augmented IL-4 and IL-10 production. Cells from HIV-infected patients produced low levels of IFN-gamma, but high levels of IL-10. The addition of anti-IL-10 did not increase Leishmania-induced proliferative responses or IFN-gamma production. Both IL-12 and/or IL-18 responses were lower in VL patients, HIV-infected, or VL-HIV co-infected patients as compared with those of healthy donors. The data suggest that the inhibitory effect of HIV and VL on proliferation and IFN-gamma production is not due to IL-10 alone, but that the defect induced by HIV and VL probably operates at the level of regulation of IFN-gamma-inducing factors, such as IL-12 and IL-18.

Predictors of unprotected sexual contacts in HIV-infected persons in Switzerland.

Predictors of sexual risk behavior with regular and casual partners among HIV-infected heterosexual and gay persons were addressed. Sociodemographic data as well as self- and interviewer-reported data on sexual behavior were obtained from 117 asymptomatic HIV-infected persons enrolled in the Zurich part of the Swiss HIV Cohort Study (SHCS). Participants who reported sexual intercourse at least once (vaginal and/or anal) without condom use in the 6 months prior to interview were considered to have risk behavior. Sexual risk behavior was analyzed separately in contacts with regular and casual partners. In the 6-month preinterview period, 92% (108 of 117) of the HIV-infected study population reported sexual contacts, and 30/117 (26%) had at least one unprotected vaginal and/or anal contact. Among 93 persons using condoms, 25% of the heterosexual and 10% of the homosexual participants reported breakage of the condom. The main predictor for unprotected sexual behavior with regular partners was an elevated number of contacts. Predictors for sexual risk behavior with casual partners were the combination of alcohol and sexual encounters and the change of sexual behavior since the epidemic of AIDS. These findings did not differ between persons with hetero- and homosexual behavior. Considering that these contacts may have passed the virus on to the seronegative population, that the probability of unsafe sex increased with the growing number of contacts, and that the number of condom breakages was remarkable, it is imperative that this group be educated and motivated to take the active role in insisting on safer sex practices in each encounter.

Role of Fas Ligand and Receptor in the Mechanism of T-Cell Depletion in Acquired Immunodeficiency Syndrome: Effect on CD4+ Lymphocyte Depletion and Human Immunodeficiency Virus Replication

AbstractDirect killing of CD4+ lymphocytes by human immunodeficiency virus-1 (HIV-1) probably cannot account for the magnitude of the loss of these cells during the course of HIV-1 infection. Experimental evidence supports a pathophysiologic role of the apoptotic process in depletion of CD4 cells in acquired immunodeficiency syndrome (AIDS). The Fas-receptor/Fas-ligand (Fas-R/Fas-L) system mediates signals for apoptosis of susceptible lymphocytes and lympoblastoid cell lines. A number of investigators have recently reported increased expression of the Fas receptor in individuals with HIV infection, along with increased sensitivity of their lymphocytes to anti-Fas antibody mimicking Fas ligand. We attempted to determine the role of Fas-mediated apoptosis in disease progression and viral replication. Increased Fas-receptor (CD95) expression on CD4+ and CD8+ lymphocytes was found in a large group of HIV-1–infected patients compared with normal controls; individuals with a diagnosis of AIDS and a history of opportunistic infection had significantly more Fas receptor expression than did asymptomatic HIV-infected persons and normal blood donor controls (P < .01). Triggering of the Fas-R by agonistic anti-Fas monoclonal antibody, CH11, was preferentially associated with apoptosis in the CD4+ cells; this effect was more pronounced in lymphocytes derived from HIV+ individuals. Soluble and membrane-bound forms of Fas-L were produced in greater amounts in peripheral blood mononuclear cells (PBMC) cultures and in plasma obtained from HIV-1–infected persons than from normal controls. Furthermore, triggering of lymphocytes from HIV-infected persons by CH11 increased levels of interleukin-1β converting enzyme (ICE), a protein associated with apoptosis. When PBMC were cultured in the presence of CH11, p24 production per number of viable cells was decreased as compared with the same PBMC without CH11 (P < .01). These findings suggest that multiple mechanisms, including increased production of Fas-L by infected PBMC, increased Fas-R expression, and induction of a protease of ICE family, may play roles in the apoptotic depletion of CD4+ cells in HIV infection.

Peripheral V gamma 9/V delta 2 T cell deletion and anergy to nonpeptidic mycobacterial antigens in asymptomatic HIV-1-infected persons.

Gamma delta T cells represent a minor population of human peripheral lymphocytes, the majority of them expressing the V delta 2/V gamma 9 TCR. Their accumulation in infectious disease lesions and their reactivity toward mycobacterial Ags suggest that V gamma 9/V delta 2 T cells play a role during infectious diseases. We have shown previously a significant expansion of the V delta 1 subset parallel to a dramatic decrease of the V delta 2 subset in PBMC from HIV-infected persons. To understand the mechanisms involved in the deletion of V delta 2 T cells, we analyzed their ability to respond in vitro to several V gamma 9/V delta 2 t cell-specific ligands. We observed that in 60% of asymptomatic HIV-infected persons, V delta 2 T cells exhibited a functional anergy to Daudi and to Mycobacterium tuberculosis stimulations. These observations were supported by the defective expansion of this subset to the recently described nonpeptidic phosphorylated Ag, TUBAg-1. Since V delta 2 responsiveness to mycobacterial Ags was shown to be normally dependent on IL-2 secretion by Th1-type CD4 T cells, the ability of IL-2 to restore V delta 2 T cells' responsiveness to TUBAg-1 was tested. V delta 2 T cell anergy persisted in spite of the presence of IL-2, and was frequently correlated with a defect in CD25 expression on stimulated V delta 2 T cells. Since V delta 2 anergy was associated with an in vivo depletion of this subset, we studied whether programmed cell death could be involved in this process, particularly because of their activated phenotype. Although peripheral V delta 2 T cells from some HIV-infected persons showed an increased susceptibility to spontaneous and activation-induced apoptosis, statistical comparison between HIV+ and HIV- donors indicated that there was no difference between both groups in the rate of V delta 2 apoptosis. Finally, V delta 2 complementarity-determining region 3 TCR analysis indicated that, in vivo, the remaining V delta 2 T cells were still polyclonal. All together these results suggest that the qualitative and quantitative alterations of the V delta 2 subset in the course of HIV infection are the consequence of a chronic antigenic stimulation, and raise the question of the contribution of a cellular ligand induced or modified by chronic HIV infection.

Why can't cytotoxic T cells handle HIV?

11) give us a glimpse of the battle. In symptomatic AIDS patients with CD4+ T-cell counts less than 500/mm3 of blood it appears that around 109 HIV virions, about one-third of the total viral load, are being produced and cleared daily. In addition, about the same number of CD4+ T cells, representing about 1% of total, are produced and destroyed daily. Decreasing the viral load to about 1% of the starting steady-state levels with drugs directed against the viral reverse transcriptase or the protease was used to reveal these dynamic figures. The antiviral treatments also revealed that drug-resistant variants emerge and reestablish the levels of viremia and the gradual CD4+ T-cell loss within a 2-week interval. This has refocused attention on the importance of the genetic variability of the pathogen, which is due to the error-prone reverse transcriptase coupled with the rate of virus replication (12). Although similar kinetic data are not available for asymptomatic HIV-infected persons, such individuals do maintain a plasma viremia, albeit 10- to 100-fold lower than that in AIDS patients, and it is likely that a similar rate of virus production from newly infected cells is occurring at this stage of HIV infection. So why can't the specific immune effectors, including CTLs, eliminate all productively infected cells? Suggestions for this have centered on the escape of the virus by epitope mutation-i.e., antigenic drift (13). This would clearly seem to be a feasible option for HIV, based on what was seen in the drug treatment studies. Another possible answer comes from studies on persistent infection of mice with lymphocytic choriomeningitis virus (LCMV), which have led to the idea that prolonged, high-level antigen exposure may exhaust the CTL response (14). The paper in this issue of the Proceedings by Moss et al. (15) reconfirms that HIVinfected individuals do maintain a high number of circulating CTLs specific for HIV epitopes. Up to 1% of the circulating CD8+ T cells score as HIV specific. In this study, sequence analysis of the T-cell receptor genes showed that some CTL

Keynote address: variations in the natural history of HIV infection.

In general, the natural history of HIV infection as revealed by prospective cohort studies such as the Multicenter AIDS Cohort Study (MACS) is consistent with our current understanding of the immunopathogenesis of HIV disease. Although the limitations of CD4+ T cell counts as a predictor of response to therapy are now recognized, enumeration of these cells remains an important predictor of outcome. Additional information regarding prognosis can be obtained using other immunological and virological information. Analysis of data from cohort studies has revealed varying patterns of CD4+ lymphocyte count decline associated with differing evidence of immune activation, specific antibody responses, CD8+ T cell responses, and level of viral burden. Of interest, some asymptomatic HIV-infected persons appear to show immune stability in the absence of therapeutic interventions. In addition, the combination of antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia (but apparently not prophylaxis for fungal or Mycobacterium avium-intracellulare infections) has prolonged survival in patients with AIDS.

Trends in hospital resource utilization by HIV-infected persons, January 1987–June 1990

Trends in the utilization of various hospital resources by HIV-infected persons between January 1987 and June 1990 have been studied to support health care planning. Data on 126 asymptomatic and symptomatic HIV-infected persons have been recorded at a patient level and analyzed at half-yearly intervals. At a hospital level, increasing utilization trends were observed. At the patient level, a decreasing utilization intensity was measured for admissions, inpatient days, inpatient diagnostic examinations, and outpatient consultations. Increasing utilization intensity was measured for care during admissions. A constant utilization intensity was observed for outpatient diagnostic examinations and inpatient medication days. Use of interventions tended to increase at the end of the study period. Discriminating between trends in the utilization of different hospital resources can improve the management of hospital health care demands of HIV-infected people.

High viral load in lymph nodes and latent human immunodeficiency virus (HIV) in peripheral blood cells of HIV-1-infected chimpanzees.

We have examined human immunodeficiency virus type 1 (HIV-1) infection in chimpanzees by analyzing HIV-1 DNA and RNA in lymph nodes and peripheral mononuclear cells (PBMCs). Like certain asymptomatic HIV-infected persons, these chimpanzees had no detectable viral replication in their PBMCs. However, viral replication and a high viral load were observed in the lymphatic tissue. Despite the absence of viral replication in PBMCs, 1/1,000 to 1/10,000 of the PBMCs contained HIV-1 proviral DNA, and HIV transcription could be rapidly induced in these cells in vitro. These results provide direct evidence of cellular latency of HIV in vivo and suggest that HIV infection in chimpanzees may be a useful model for clinical latency of HIV infection in humans.

Cognitive changes associated with the acquired immunodeficiency syndrome

T HE ACQUIRED immunodeficiency syndrome (AIDS), a result of infection with the human immunodeficiency virus (HIV), disrupts immunological and neurological functioning (Merrill C Rosenberg & Fauci, 1991; Swanson, Cronin-Stubbs, & Colletti, 1990). Cognitive or neuropsychological impairment has been reported in 40% to 60% of persons with AIDS and in a subset of persons with AIDS-related complex (ARC), an HIV-induced syndrome involving the central nervous system (CNS) that is characterized by fever and weight loss. However, it is not clear whether or not cognitive impairment is present in asymptomatic HIV-infected persons. Therefore, the purposes of this study were (a) to determine the number and percentage of individuals exhibiting neuropsychological impairment at four stages of HIV infection and (b) to determine if a relationship exists between stage of HIV infection and cognitive functioning.

Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine.

The Centers for Disease Control recommends that, because of a greatly increased susceptibility to pneumococcal infection, all persons infected with human immunodeficiency virus (HIV) receive pneumococcal vaccine. Using an ELISA specific for antibody to capsular polysaccharide, a postvaccination antibody was evaluated to five commonly infecting serotypes of Streptococcus pneumoniae. Thirty-nine HIV-infected persons with less than or equal to 500 CD4 cells exhibited significantly fewer responses than did healthy controls; overall, only 46 (24%) of 195 possible responses were positive compared with 45 (75%) of 60 in 12 HIV-infected subjects with greater than 500 CD4 cells and 92 (74%) of 125 in 25 healthy controls (P less than .001). Subjects with less than or equal to 500 CD4 cells responded to a mean of 1.1 antigens versus a mean of 3.8 and 3.7 in those with greater than 500 CD4 cells and controls, respectively (P less than .001). There were no differences between responses in those with less than 200 and those with 200-500 CD4 cells. Within groups stratified by CD4 cell counts, further stratification by clinical status did not reveal significant differences. Since asymptomatic HIV-infected persons with less than 500 CD4 cells show abnormal responses, pneumococcal vaccine should be given when HIV infection is first detected.

The management of early human immunodeficiency virus infection

The outcome of treatment in patients with early asymptomatic HIV disease has recently improved. Clinical trials with zidovudine have demonstrated efficacy and greatly reduced toxicity when the drug is used in asymptomatic HIV-infected persons who have fewer than 500 CD4+ cells/mm3, and resistance to this drug in these patients is less frequent and severe. Also, the optimum dosage of zidovudine is less than previously believed, probably in the range of 500-600 mg daily given in oral divided doses. The use of antibiotics to prevent Pneumocystis carinii pneumonia is also of clear value in HIV-infected asymptomatic or symptomatic persons with fewer than 200 CD4+ cells/mm3. Oral regimens such as trimethoprim/sulfamethoxazole or dapsone alone appear to be effective and are gaining preference over aerosolized pentamidine that is considerably more expensive. Together these medical advances argue for the encouragement of voluntary HIV testing to enable early diagnosis and, hence, optimum medical monitoring and appropriate intervention. These issues and recommendations for laboratory and clinical monitoring will be provided in this review.

Recent advances in the medical management of early HIV disease

The management of patients who have HIV disease, particularly those in early, asymptomatic disease stages, has recently improved. Clinical trials with zidovudine have demonstrated efficacy and greatly reduced toxicity when the drug is used for asymptomatic HIV-infected persons who have fewer than 500 CD4+ cells/mm3. Also, the optimum dose of zidovudine is lower than previously believed, probably in the range of 300-500 mg daily in oral divided doses. The use of antibiotics to prevent Pneumocystis carinii pneumonia (PCP) is also of clear value for HIV-infected asymptomatic or symptomatic persons with fewer than 200 CD4+ cells/mm3. While aerosolized pentamidine is the only regimen approved for PCP prophylaxis, oral drugs, such as trimethoprim/sulfamethoxazole or dapsone, also appear effective. Together, these and similar advances argue for the widespread use of voluntary HIV testing to enable optimum medical monitoring and appropriate intervention. These issues and recommendations for laboratory and clinical monitoring are provided in this review.