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Response to treatment, mortality, and CD4 lymphocyte counts in HIV-infected persons with tuberculosis in Abidjan, Côte d'Ivoire.

We examined the severity of immune deficiency in patients with HIV-associated tuberculosis in Côte d'Ivoire and assessed its effect on mortality and response to treatment. Consecutive patients attending a tuberculosis treatment centre in Abidjan with smear-positive pulmonary or clinically diagnosed extrapulmonary tuberculosis were tested for HIV-1 and HIV-2 infections and had CD4 lymphocyte counts measured. Patients received standard short-course chemotherapy. Analysis of outcome (restricted to smear-positive tuberculosis patients) was done at 6 months. The 247 HIV-positive patients were significantly more likely than the 312 HIV-negative patients to have CD4 lymphocyte counts of less than 200/microL (43% vs 1%; odds ratio 56.9; [95% CI 19.7-185.3]) and 200-499/microL (39% vs 14%, odds ratio 3.8; [2.5-5.9]). Among HIV-positive patients, median CD4 lymphocyte counts in those with extrapulmonary tuberculosis (198/microL; n = 67) was lower, but not significantly so, than among those with pulmonary tuberculosis (257/microL; n = 180). Among 460 patients with pulmonary tuberculosis, the overall mortality rate was significantly higher in HIV-positive than HIV-negative persons (6% vs 0.4%; relative risk 17.1 [2.2-131.4]), and increased with the severity of immune deficiency; mortality rates in HIV-positive patients with CD4 counts of < 200/microL and 200-499/microL were 10% and 4%, relative risk 27.6 (3.5-220.8); and 11.5 (1.2-109), respectively, compared to HIV-negatives. Among patients completing treatment, cure rates were similar in HIV-positive patients (93%) and HIV-negative patients (92%), and were not related to CD4 counts. Severity of immune deficiency was the major determinant of mortality in HIV-associated tuberculosis. Among people completing treatment, microbiological response was satisfactory irrespective of serological or immune status.

AIDS-Related Opportunistic Infections↗

Initial low CD4 lymphocyte counts in recent human immunodeficiency virus infection and lack of association with identified coinfections.

Initial CD4 lymphocyte counts were studied in 244 patients with human immunodeficiency virus (HIV) seroconversion. The CD4 cell counts at initial presentation after seroconversion were normally distributed (mean, 579/mm3; SD, 252). The mean percentage of CD4 cells was 26.1% (SD, 5.6). CD4 cell counts were < 500/mm3 in 41% and < 200/mm3 in 4%. The mean calculated duration of HIV infection was 7.7 months, which was not significantly different between the highest and lowest CD4 count quartiles (8.1 vs. 7.9). Age, sex, race, and serologic evidence of toxoplasmosis, cytomegalovirus, hepatitis B, syphilis, and varicella-zoster virus were not associated with initial low CD4 cell counts; however, never-married men were significantly overrepresented in the lowest quartile. These findings suggest that extensive CD4 lymphocyte depletion is common in early HIV infection and that frequent screening is necessary to identify newly infected patients who would benefit from antiretroviral therapy.

Adult↗

CD4 lymphocyte count in HIV-positive persons exposed to Cryptococcus neoformans.

A report is presented on four HIV-positive homosexual men examined after several months of exposure during cleaning of a flat from masses of pigeon droppings heavily colonized by Cryptococcus neoformans. Only one out of the four persons, with a CD4 lymphocyte count of 50/microL, fell sick from systemic cryptococcosis, but not the others, with CD4 lymphocyte counts of 180, 250, and 630/microL, respectively; they remained clinically and mycologically inconspicuous and free from C. neoformans. Open questions in view of the epidemiology of opportunistic pathogens in AIDS are discussed with regard to the CD4 cell count as a parameter indicating a predisposition for cryptococcosis as an airborne AIDS-defining opportunistic infection. This has been confirmed by specific cultural diagnosis of the agent in both the environment and the patient. Already in 1987/88, the probable source of infection had been the subject of epidemiological studies on C. neoformans in Berlin.

AIDS-Related Opportunistic Infections↗

Increased serum lipids are associated with higher CD4 lymphocyte count in HIV-infected women.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has been associated with dyslipidaemia; however, the roles of immune status and non-HIV-disease risk factors remain unclear. METHODS: A cross-sectional analysis of fasting lipids was carried out for 231 women, of whom 132 were HIV-infected and 99 were uninfected. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B (apo B) were measured. CD4 lymphocyte count, hepatitis C status, demographics, diet, and anthropometrics were also assessed. RESULTS: A total of 132 women were HIV-infected [30 were antiretroviral-naive, 68 were on protease inhibitors (PIs), and 34 were on non-PI HAART]. HIV infection was associated with higher triglycerides, lower HDL-C, and, among obese women, higher total cholesterol and LDL-C. Non-PI and PI HAART were each independently associated with higher total cholesterol, LDL-C, and apo B, compared with being ART-naive. Among HIV-infected women, after adjustment for HAART use, women with a CD4 lymphocyte count > or =500 cells/microL had total cholesterol 41.8 mg/dL (P = 0.002) and LDL-C 28.8 mg/dL (P = 0.01) higher, on average, than women with a CD4 count <200 cells/microL. Women with a CD4 count of 200-499 cells/microL had total cholesterol 26.31 mg/dL higher, on average, than those with a CD4 count <200 cells/microL (P = 0.04), although differences in LDL-C did not reach significance (15.51 mg/dL; P = 0.12). A higher CD4 count was also associated with higher apo B (P < 0.001). Active hepatitis C infection was associated with lower total cholesterol, LDL-C, triglycerides, and apo B. CONCLUSIONS: Higher CD4 lymphocyte counts were associated with higher lipid levels, suggesting that immune competence may independently affect the dyslipidaemia seen in the HAART era. In addition, it is important that hepatitis C status be assessed in studies of dyslipidaemia in the HIV-infected population.

Adult↗

Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl.

OBJECTIVE: To assess rates of sexual activity, contraceptive use, genital infections and dysplasia, and other gynecologic symptoms among well-characterized populations of HIV-seropositive women enrolled in two Adult AIDS Clinical Trials Group (AACTG) randomized studies. METHODS: Gynecologic data were collected using standardized interview and examination forms from women enrolled in two protocols: ACTG 175, an antiretroviral trial (CD4+ lymphocyte counts 200-500 cells/microl) and ACTG 196, a Mycobacterium avium complex prophylaxis trial (CD4+ counts < or =100 cells/microl). RESULTS: Women enrolled in the two studies were similar in age, race, weight, and history of illicit or injection drug use, but women in ACTG 196 (n = 67) had lower median CD4+ counts (median, 35 cells/microl; range, 0-135 cells/microl versus median, 356 cells/microl; range, 131-620 cells/microl; p < .0005), were less likely to be antiretroviral naive (6% versus 38%; p < .0005), and were more likely to have a Karnofsky score <80 (28% versus 5%; p < .0001) than women in ACTG 175 (n = 185) at baseline. Recent changes in menstrual cycle were not different between groups. Women enrolled in ACTG 196 were less likely to be sexually active (40% versus 61%; p < .005), but both groups reported high levels of contraceptive use. Papanicolaou smear results in ACTG 196 and ACTG 175 respectively, were: normal, 38% and 50%, atypia, 24% and 39%, low-grade squamous intraepithelial lesions (SIL), 27% and 10%, and high-grade SIL, 11% and 0.7% (p < .001). CONCLUSIONS: Gynecologic complications are common among HIV-seropositive women with CD4+ lymphocyte counts < 500 cells/microl and are more common and severe among those with more advanced immunosuppression.

Adult↗

Changes in CD4 lymphocyte counts after interruption of therapy in patients with viral failure on protease inhibitor-containing regimens. Royal Free Centre for HIV Medicine.

OBJECTIVE: To describe the short-term changes in CD4 lymphocyte counts after the interruption of antiretroviral HIV therapy in order to increase the understanding of CD4 lymphocyte dynamics, and so that appropriate monitoring strategies can be designed. METHODS: We studied 35 HIV-infected patients with late-stage disease who had therapy interruptions leading to high viral load levels, median greater than 750 000 RNA log10 copies/ml, and in whom two CD4 cell counts (median 28 days apart) were available before beginning a salvage regimen. RESULTS: Overall, there was a substantial decline in CD4 cell counts from a median of 125 to 83 cells/mm3 in the average 28 day period, with median proportionate and absolute losses of 26% and 24 cells/mm3 per month, respectively (P < 0.008). This tended to be greater in individuals studied sooner after interrupting therapy (P = 0.03) and in those with CD4 cell counts above the pre-therapy baseline (P = 0.06). There was a strong negative correlation between the proportionate increase in viral load and the absolute change in CD4 cell count (-0.66, P = 0.0002). CONCLUSION: Patients with relatively advanced HIV infection interrupting antiretroviral therapy after failing a protease inhibitor-containing regimen require frequent monitoring because CD4 cell counts appear to fall quite rapidly, at least in the first few weeks after interruption.

Adult↗

Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age.

OBJECTIVE: To examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. DESIGN: A prospective study. HIV-infected children were enrolled during the first year of life and followed for more than 2 years at the Queen Elizabeth Central Hospital in Blantyre, Malawi (southeast Africa). METHODS: Morbidity and mortality information was collected every 3 months, and physical examination and blood testing (for viral level and CD4 cell percentage) were performed every 6 months. Kaplan-Meier analyses and proportional hazards models were used to estimate survival and to examine the association of primary predictors with mortality. RESULTS: Of 155 HIV-infected children originally enrolled, 115 (74%) had viral load testing and 82 (53%) had both viral load and CD4 cell percentage testing after their first year. Among children over one year of age, significant associations were found between mortality and the log10 viral load and CD4 cell percentage in both univariate and multivariate models. Independent of the CD4 cell value, a one unit log10 increase in HIV RNA level increased the hazard of child mortality by more than twofold. Children with low CD4 cell counts (< 15%) and high viral loads (> or = 250,000 copies/ml median value) had the worst survival; children with high CD4 cell counts (> or = 15%) and low viral loads (< 250,000 copies/ml) had the best survival. CONCLUSION: As in developed countries, viral load and CD4 cell count are the main predictors of mortality among African children. Making these tests available adds to the challenges to be considered if antiviral therapies were to be adopted in these countries.

CD4 Lymphocyte Count↗

Long-term methadone treatment: effect on CD4+ lymphocyte counts and HIV-1 plasma RNA level in patients with HIV infection.

The objective was to examine the effect of methadone on CD4+ lymphocyte counts and viral load and to expect to document the safety of methadone maintenance in patients with human immune deficiency syndrome. This is a retrospective chart analysis comparing the trends in CD4+ count and viral load in two populations of 21 human immunodeficiency virus (HIV) infected patients, one on methadone maintenance and a methadone non-using group. Each methadone user was matched with a control methadone non-user that had a similar CD4+ at the beginning of the study. For the CD4+ count we compared the slope of regression for each couple of patients. In 15 patients we also collected the viral load, which was measured at 4-6 monthly intervals. The mean length of follow-up was 811 days for the methadone group and 797 days in the control group. There was no statistical difference in the treatment received by the two groups of patients during the study. The slope of regression of CD4+ count showed a significantly steeper decline in the methadone-using patients compared with the methadone non-users (r= 0.487; p< 0.05). The evolution of the HIV-1 RNA levels was the same during the follow-up of mean 186 months in a few of the patients in each of the two groups. Long-term methadone use was associated with a significantly faster decrease of CD4+ count in HIV-1 affected patients compared with methadone non-users. HIV-1 RNA data were found in too few patients to enable any conclusions about the development of viral load in the two groups.

Adult↗

CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3.

BACKGROUND: The optimal timing of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients with > or = 200 absolute CD4 lymphocytes/mm3 is unknown. CD4 lymphocyte percentage could add prognostic information. METHODS: Persons who initiated HAART between 1 January 1998 and 1 January 2003, received > or = 30 days of therapy, and had baseline CD4 lymphocyte data available were included in the study. The log-rank test for time to event and Cox proportional hazards models were used to determine predictors of a new acquired immunodeficiency syndrome-defining illness or death. RESULTS: A total of 788 patients met the inclusion criteria. At baseline, subjects had a median of 225 CD4 lymphocytes/mm3 and 17% CD4 lymphocytes. Subjects with < 17% CD4 lymphocytes had earlier disease progression, compared with subjects with > or = 17%, both in the entire cohort (P<.0001) and of those subjects with > 350 absolute CD4 lymphocytes/mm3 at baseline (P=.03). CD4 lymphocyte percentage < 17% was the strongest predictor of disease progression among subjects in this latter group (hazard ratio, 3.57; P=.045). CONCLUSIONS: In this cohort, CD4 lymphocyte percentage predicted disease progression in HIV-infected subjects who initiated therapy with > 350 CD4 lymphocytes/mm3. This information may help identify persons who will derive the greatest benefit from initiation of HAART.

Adolescent↗

CD4 lymphocyte count as an indicator of delay in seeking human immunodeficiency virus-related treatment.

BACKGROUND: As many as half of patients infected with the human immunodeficiency virus who are medically eligible for Pneumocystis prophylaxis and zidovudine treatment have not received these treatments. We used the CD4 lymphocyte count as an indicator of delay in seeking treatment among patients infected with human immunodeficiency virus and assessed whether insurance status was associated with the stage of illness when care is initiated. METHODS: Data from 96 patients who initiated medical care at a university acquired immunodeficiency syndrome clinic from August 1989 to January 1991 were retrospectively reviewed. RESULTS: Patients initiated care at a relatively late stage of illness (mean CD4 lymphocyte count, 0.37 x 10(9)/L [369/mm3]), and 29% were below the threshold for Pneumocystis prophylaxis. Patients with private insurance had significantly lower CD4 counts (mean, 0.27 x 10(9)/L) than did individuals with public insurance (mean, 0.46 x 10(9)/L). CD4 counts did not increase during the 18-month study period. CONCLUSIONS: The majority of patients infected with human immunodeficiency virus are eligible for medical therapy and could benefit by initiating care sooner. Private insurance was not associated with initiating early care, supporting anecdotal reports that some privately insured individuals may be reluctant to seek care for a human immunodeficiency virus-related condition.

Adult↗

Survival in children with perinatal HIV infection and very low CD4 lymphocyte counts.

OBJECTIVES: To evaluate clinical conditions associated with mortality in HIV-infected children with CD4+ counts <100 cells/microl. METHODS: The Pediatric Spectrum of HIV Disease Project is a longitudinal medical record review study with eight study sites in the United States, which have been enrolling children since 1989. Survival time from baseline very low CD4 count (<100 cells/microl) to death was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the effect of clinical variables on mortality. RESULTS: Of 522 children (>/=1 year of age) with serial CD4+ T-lymphocyte measurements, the median age at the first very low CD4 count was 4.8 years. The estimated median survival following the first very low CD4 count was 36 months. The following factors present at the first very low CD4 count were independently associated with a higher risk of death: younger age, weight-for-age >2 standard deviations below the mean, and previously diagnosed AIDS. The subsequent development of cytomegalovirus (CMV)-associated disease, Mycobacterium avium intracellulare (MAI) infection, wasting syndrome, or esophageal candidiasis was also independently associated with a higher risk of death. CONCLUSION: Survival in HIV-infected children with very low CD4 counts before introduction of highly active antiretroviral therapy was highly variable. Poor nutritional status and the development of CMV disease or MAI infection were associated with the shortest survival times.

Age Factors↗

Predominance of detrimental humoral immune responses to HIV-1 in AIDS patients with CD4 lymphocyte counts less than 400/mm3.

The humoral immune response to human immunodeficiency virus type 1 (HIV-1) was studied in 25 AIDS patients with CD4 lymphocyte counts of less than 400/mm3. Humoral immune responses against tissue culture adapted strains of HIV-1, and two limited-passage patient isolates were investigated. Total anti-HIV antibody levels were not significantly different between different individuals. Neutralizing titres against HIVLA1 and HIVSF2 were 10- to 100-fold higher than against clinical isolates. The complement-mediated, antibody-dependent enhancement of HIV-1 infection titre was high (mean 1:14,000). Antibody-complement mediated cytotoxicity of both HIVLA1 and HIVSF2 was ineffective using human complement as a complement source. The antibody-dependent, cell-mediated cytotoxicity (ADCC) activity varied against the four isolates with tissue culture-adapted strains being more susceptible than clinical isolates. Finally, an ADCC effector cell function, natural killer or NK activity, was measured for all 25 patients, and NK activity of patients was decreased by nearly 75% compared to uninfected individuals. In summary, beneficial humoral immune responses are low in HIV-1 infected individuals with CD4 counts of less than 400/mm3 if the in vitro assay system is constructed to best mimic the in vivo situation. These results suggest that the lack of functional antibody responses to HIV may play an important role in viral pathogenesis.

Acquired Immunodeficiency Syndrome↗

Oral soft tissue manifestations and CD4 lymphocyte counts in HIV-infected children.

This study investigated the prevalence of oral soft tissue lesions in children infected with HIV and the relationship of CD4 lymphocyte levels with the prevalence of those lesions. Sixty HIV-positive children enrolled in the Children's Hospital AIDS Program (age 5.8 +/- 3 years) were selected for study. Only five subjects (8%) had healthy gingiva and a low mean plaque index (22%). The remainder had gingivitis or periodontitis with relatively high plaque indices (47, 55, and 94%, respectively). A declining CD4 lymphocyte count (1357 to 35) was associated with an increasing severity of gingival disease.

AIDS-Related Opportunistic Infections↗

Genetic polymorphisms in CX3CR1 predict HIV-1 disease progression in children independently of CD4+ lymphocyte count and HIV-1 RNA load.

BACKGROUND: The impact of CX3CR1 polymorphisms on human immunodeficiency virus type 1 (HIV-1) pathogenesis is controversial, with conflicting reports of their role in disease progression in HIV-1-infected adults. METHODS: A cohort of 1055 HIV-1-infected children were genotyped for 2 CX3CR1 polymorphisms, V/I249 and T/M280, and their impact on HIV-1-related disease progression, including central nervous system (CNS) impairment, was evaluated. RESULTS: Children with the CX3CR1 I/I249 genotype experienced more-rapid disease progression (I/I249 vs. V/V249: relative hazard [RH], 2.19 [95% confidence interval {CI}, 1.30-3.68], P=.003; I/I249 vs. V/I249: RH, 1.77 [95% CI, 1.00-3.14], P=.05) and a trend toward more CNS impairment (I/I249 vs. V/V249: RH, 2.19 [95% CI, 1.00-4.78], P=.049; I/I249 vs. V/I249: RH, 2.02 [95% CI, 0.85-4.83], P=.11). Children with the V249-T280 haplotype experienced significantly less disease progression (RH, 0.42 [95% CI, 0.24-0.73]; P=.002) and CNS impairment (RH, 0.39 [95% CI, 0.39-0.22]; P=.001). Of note, these effects remained significant after CD4+ lymphocyte count and plasma HIV-1 RNA load at baseline were adjusted for and in a longitudinal, multivariate analysis. CONCLUSIONS: CX3CR1 genotypes and haplotypes impact HIV-1 disease progression independently of CD4+ lymphocyte count and plasma HIV-1 RNA load, suggesting that the fundamental role of CX3CR1 in the alteration of disease progression might be the recruitment of immunomodulatory cells responsible for the control of HIV-1.

CD4 Lymphocyte Count↗

Relationship of neurological manifestations, CD4+ lymphocyte count and plasma viral load in HIV infected patients.

The aim of the study was to assess the relationship between the neurological manifestations of HIV infection, CD4+ lymphocyte count and the levels of HIV-1 RNA (viral load) in plasma. A total of 62 adult antiretroviral naïve HIV infected patients were enrolled in the study. Among them 26 had neurological complications of HIV infection (1st group), 16 patients had symptomatic disease without neurological involvements (2nd group) and 20 were asymptomatic patients (control group). Measurement of CD4 count was performed by indirect immunofluorescent assay by using the monoclonal antibodies and viral load (VL) in plasma--by RT PCR method. CD4 count was significantly lower in the 1st and 2nd group compared to the control group. There was correlation between the level of CD4 count and type of neurological manifestation. VL was comparable between the 1st and 2nd groups and was higher than in control group. There is a significant correlation between the level of CD4 count and type of neurological manifestation of HIV infection. Presence of neurological complication as well as other clinical manifestations is associated with decreased CD4 count and increased VL. Level of CD4 count can serve as an indicator for initiation of prophylaxis treatment of certain opportunistic pathogens.

Adult↗

Recombinant human gamma interferon in human immunodeficiency virus-infected children: safety, CD4(+)-lymphocyte count, viral load, and neutrophil function (AIDS Clinical Trials Group Protocol 211).

Nineteen children with human immunodeficiency virus (HIV) infection were treated with recombinant human gamma interferon (rIFN-gamma) (50 microg/m2 subcutaneously three times each week during weeks 1 through 12 and 100 microg/m2 subcutaneously three times each week during weeks 13 through 24) in a phase I/II clinical trial. All children continued to receive previously prescribed therapy with oral zidovudine or didanosine. Children were assessed clinically and with laboratory studies during 24 weeks of study treatment and for 12 weeks after completion of rIFN-gamma therapy. In general, rIFN-gamma therapy was well tolerated. There were two clinical or laboratory adverse events thought to be possibly or probably study drug associated. One child developed acute pancreatitis; another child developed granulocytopenia. Median CD4(+)-lymphocyte counts and plasma HIV RNA concentrations did not change significantly during therapy. In vitro neutrophil bactericidal activity against Staphylococcus aureus and superoxide production were not significantly affected by rIFN-gamma therapy. We conclude that rIFN-gamma therapy in HIV-infected children receiving single-agent antiretroviral therapy is safe and does not produce consistent changes in CD4(+)-lymphocyte count, plasma HIV RNA concentration, or in vitro neutrophil function.

Anti-HIV Agents↗

Low CD4 lymphocyte count in a patient with P. carinii pneumonia after autologous bone marrow transplantation.

Authors report a case of P. carinii pneumonia in a child with 5% CD4 lymphocytes (absolute number 5/microliters) after autologous bone marrow transplantation followed by pulmonary irradiation. Serial evaluation of CD4 lymphocyte count or percentage or, at least, detection of significant and persistent lymphopenia could be useful for detecting a high risk of developing P. carinii pneumonia.

Antineoplastic Combined Chemotherapy Protocols↗

Use of beta 2-microglobulin level and CD4 lymphocyte count to predict development of acquired immunodeficiency syndrome in persons with human immunodeficiency virus infection.

Serum beta 2-microglobulin (beta 2M) levels were measured by radioimmunoassay in 962 unmarried men recruited by probability sampling from areas in San Francisco, Calif, most severely affected by the epidemic of acquired immunodeficiency syndrome (AIDS). From July 1984 to December 1987, 65 incident AIDS cases occurred in 388 homosexual/bisexual men infected by the human immunodeficiency virus (HIV) at the time of recruitment. The mean level of beta 2M in uninfected individuals at entry was 170 nmol/L. In HIV-seropositive patients who had not developed AIDS, the mean beta 2M level was 254 nmol/L, and in those who had developed AIDS, the beta 2M level was 347 nmol/L. After 36 months of follow-up, 34% of individuals with beta 2M levels greater than 322 nmol/L at entry developed AIDS, 21% of individuals with levels between 246 and 322 nmol/L developed AIDS, while only 7.3% of those with levels below 246 nmol/L developed AIDS. The beta 2M level predicted the development of AIDS independently of the CD4 lymphocyte count in HIV-seropositive individuals. Thus, 65.5% of HIV-seropositive individuals with beta 2M levels above 322 nmol/L and CD4 lymphocyte counts of below 500/microL developed AIDS in 3 years. This represents an 18.4-fold increased relative hazard at 3 years over individuals with beta 2M and CD4 cell counts within the reference range for uninfected individuals. A nomogram is provided that allows the easy calculation of the probability of an HIV-infected person developing AIDS in 36 months depending on prevalent levels of CD4 lymphocytes and serum beta 2M.

Acquired Immunodeficiency Syndrome↗