Relapse rates after short-course (6-month) treatment of tuberculosis in HIV-infected and uninfected persons.

OBJECTIVE: To determine the rate of tuberculosis relapse among HIV-seropositive and -seronegative persons treated for active tuberculosis with short-course (6-month) therapy. DESIGN: Consecutive cohort study. SETTING: City of Baltimore tuberculosis clinic. PATIENTS: Tuberculosis patients treated between 1 January 1993 and 31 December 1996. INTERVENTION: Patients received 2 months of isoniazid, rifampin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampin. MAIN OUTCOME MEASURE: Passive follow-up for tuberculosis relapse was performed through September 30, 1998. RESULTS: There were 423 cases of tuberculosis during the study period; 280 patients completed a 6-month course of therapy. Therapy was directly-observed for 94% of patients. Of those who completed therapy, 47 (17%) were HIV-seropositive, 127 (45%) were HIV-seronegative, and 106 (38%) had unknown HIV status. HIV-infected patients required more time to complete therapy (median 225 versus 205 days; P = 0.04) but converted sputum culture to negative within the same time period (median 77 versus 72 days; P = 0.43) as HIV-seronegative or unknown patients. Relapse occurred in three out of 47 (6.4%) HIV-infected patients compared to seven out of 127 (5.5%) HIV-seronegative patients (P = 1.0). Relapse rates also did not differ when HIV-seropositive patients were compared with HIV-seronegative and patients with unknown HIV status (6.4% versus 3.0%; P = 0.38). Of the 10 patients with tuberculosis relapse, restriction fragment length polymorphism data were available for five; all five relapse isolates matched the initial isolate. CONCLUSIONS: These results support current recommendations to treat tuberculosis in HIV-infected patients with short-course (6-month) therapy.     

Impact of HIV infection on invasive cervical cancer in Kenyan women

OBJECTIVES: To determine the association between invasive cervical cancer (ICC) and HIV infection in Kenyan women. STUDY DESIGN: Case-control, with ICC patients as cases, and women with uterine fibroids as controls. METHODS: Medical and socio-demographic data were collected from 367 ICC patients, and 226 women with fibroids. After informed consent, HIV testing was done. RESULTS: ICC patients were older than fibroid patients (48 versus 41 years; P < 0.001), with an HIV seroprevalence of 15% and 12% respectively (P > 0.05). However, cases younger than 35 years were 2.6-times more likely to be HIV positive than controls of similar age [35% versus 17%; odds ratio (OR), 2.6; P = 0.043]. ICC HIV-seropositive patients were, on average, 10 years younger than HIV-seronegative patients (40 versus 50 years; P < 0.001). Eighty per cent of HIV-seropositive and 77% of HIV-seronegative ICC patients were in FIGO stage IIb or above. However, the odds of having poorly differentiated tumours was three times higher for HIV-seropositive than for HIV-seronegative ICC patients (77% versus 52%; OR, 3.1; P = 0.038) after adjusting for histological cell type and clinical stage. Mean CD4 cell count was 833 x 10(6) cells/l in ICC and 1025 x 10(6) cells/l in fibroid patients (P = 0.001). CONCLUSION: Young women with ICC were more often HIV infected than women with fibroids of the same age groups. HIV infection was associated with poor histological differentiation of the tumours. These findings suggest an accelerated clinical progression of premalignant cervical lesions to ICC in HIV-infected women.     

Human immunodeficiency virus infection in tuberculosis patients

Human immunodeficiency virus (HIV) serology was performed in non-Asian-born patients 18-65 years old with newly diagnosed tuberculosis at a county tuberculosis clinic, and demographic and clinical features of HIV-seropositive and HIV-seronegative patients were compared. Sixty of 128 eligible patients agreed to participate, of whom 17 (28%) were seropositive. Risk of HIV was associated with homosexual contact, intravenous drug use, or both; however, 4 (24%) of the 17 seropositives denied risk behaviors. Significantly more blacks (48%) than whites (10%) or Latinos (20%) were HIV-seropositive (P less than .01). Site of disease, tuberculin reactivity, response to therapy, drug toxicity, and relapse did not differ significantly between groups. HIV-seropositive patients had significantly lower median CD4+ cell counts (326/mm3, range 23-742/mm3, vs. 929/mm3, range 145-2962/mm3, P less than .0005) and median CD4+:CD8+ ratios (0.50, range 0.14-1.07 vs. 1.54, range 0.35-4.36, P less than .0001). HIV infection is associated with clinically typical tuberculosis and HIV screening of tuberculosis patients is recommended in areas where HIV is endemic.     

Differences in laboratory values in HIV infection by sex, race, and risk group.

OBJECTIVES: To determine differences in CD4+ and CD8+ lymphocyte values, beta 2-microglobulin (beta 2M), and HIV p24 antigenemia by sex and race among HIV-seropositive and HIV-seronegative injecting drug users (IDU), and to compare these values with those in homosexual men of equivalent status. DESIGN: Baseline values from a cohort of 206 HIV-seropositive and 173 HIV-seronegative IDU were compared with values from a cohort of 288 HIV-seropositive homosexual men and 176 HIV-seronegative controls, who were prospectively followed at 6-month intervals, to examine differences in laboratory values in HIV-infected individuals by sex, race, and risk group. METHODS: Among HIV-seropositives, we compared white and black IDU only (n = 167), and white male IDU (n = 38) with white homosexual men (n = 256). Laboratory values from the cohort of homosexual men at 24, 36 and 48 months of follow-up were compared with IDU values. RESULTS: HIV-infected female IDU had significantly higher CD4+ lymphocyte counts (P < 0.03) and percentages of CD4+ lymphocytes (P < 0.004) than male IDU, resulting in higher CD4:CD8 ratios (P < 0.002). White IDU had significantly higher serum beta 2M levels than black IDU (P < 0.02). Black female IDU were much less likely to be HIV p24-antigenemic (1%) than all other groups (P < 0.005). Compared with homosexual men, male IDU had significantly elevated beta 2M levels (0.58 mg/l higher). When controlled for CD4+ lymphocyte values as a surrogate for length of time HIV-infected, beta 2M and HIV p24 antigenemia differences persisted. CONCLUSIONS: These differences should be considered when HIV p24 antigen, CD4+ lymphocyte counts and beta 2M levels are used as surrogate markers in clinical trials and management of HIV disease.     

A retrospective cohort study of the risk of tuberculosis among women of childbearing age with HIV infection in Zaire

To determine the risk of active tuberculosis associated with HIV infection, we retrospectively studied a cohort of HIV-seropositive and HIV-seronegative women participating in an HIV perinatal transmission study in Kinshasa, Zaire. After a median follow-up of 32 months, new cases of proven pulmonary or clinically diagnosed tuberculosis occurred in 19 of the 249 HIV-seropositive women (7.6%, 3.1 cases per 100 person-years) compared with 1 of the 310 HIV-seronegative women (0.3%, 0.12 cases per 100 person-years), for a relative risk of 26 (95% confidence interval, 5 to 125). Proven pulmonary tuberculosis was diagnosed in 7 HIV-seropositive women (2.8%, 1.2 cases per 100 person-years) and 1 HIV-seronegative woman (0.3%, 0.12 cases per 100 person-years), for a relative risk of 10 (95% confidence interval, 1.5 to 47). We estimated that 66 cases of proven pulmonary tuberculosis in 100,000 person-years of follow-up in women of childbearing age could be attributed to HIV; this is 35% of their estimated total incidence of proven pulmonary tuberculosis. Among those followed for 2 yr, 27 (11%) of 243 HIV-seropositive women died during 2 yr of follow-up compared with none of 296 HIV-seronegative women (p less than 0.001). In HIV-seropositive women with proven or clinically diagnosed tuberculosis mortality was even higher: 5 (26%) of the 19 HIV-seropositive women with proven pulmonary or clinically diagnosed tuberculosis died during follow-up compared with 22 (10%) of the 224 HIV-seropositive women not diagnosed as having tuberculosis (relative risk 2.7; 95% confidence interval, 1.1 to 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)     

The incidence of tuberculosis in drug users with small tuberculin reaction sizes.

SETTING: In persons infected with the human immunodeficiency virus (HIV), a decreased tuberculin reaction cut-point of > or = 5 mm induration is recommended. OBJECTIVE: To determine tuberculosis risk in non-anergic HIV-infected persons with 5-9 mm tuberculin reactions. DESIGN: A prospective study with semi-annual tuberculin and anergy testing, HIV antibody and T cell subset assays, and active surveillance for tuberculosis. RESULTS: Participants were 572 HIV-seronegative and 241 HIV-seropositive non-anergic drug users. No tuberculosis occurred in HIV-seronegative persons. Tuberculosis incidence among HIV-seropositive drug users was 3.3, 7.7, 0, and 0.34 per 100 person-years in those with tuberculin reaction sizes of > or = 10 mm, 5-9 mm, 1-4 mm, and 0 mm, respectively, and was significantly increased in persons with 5-9 mm induration compared with those with 0-4 mm induration (rate ratio 27.7, 95%CI 2.9-268). Among persons with reaction sizes of 5-9 mm, tuberculosis occurred exclusively in those with CD4+ lymphocyte counts <500/mm3 at the time of their 5-9 mm tuberculin reactions. CONCLUSION: HIV-infected persons with tuberculin reaction sizes of 5-9 mm are at increased risk for tuberculosis compared to non-anergic persons with smaller (0-4 mm) reaction sizes. However, this increased risk may be limited to those with low CD4+ lymphocyte counts at the time of tuberculin testing.     

The chest roentgenogram in pulmonary tuberculosis patients seropositive for human immunodeficiency virus type 1

To determine the impact that co-infection with HIV has on the radiographic presentation of pulmonary tuberculosis, we examined the chest roentgenograms obtained before treatment in 225 HIV-tested adult Haitians with bacillary (smear or culture or both) positive pulmonary tuberculosis. There were 67 HIV-seropositive and 158 HIV-seronegative patients. Intrathoracic adenopathy alone was more common and parenchymal infiltrates less common in HIV-seropositive patients (p less than 0.05). Although a parenchymal infiltrate was less likely to be cavitating in the HIV-seropositive group (p less than 0.05) when cavitary parenchymal disease was present, HIV seropositivity did not affect the number of cavities (single or multiple) or the size of the largest cavity. Patients with AIDS were significantly more likely to have a chest radiographic pattern consistent with primary tuberculosis (80 percent) than HIV-seropositive patients without AIDS (30 percent), and the latter were significantly more likely to have such a pattern than HIV-seronegative patients (11 percent) (p less than 0.05). The HIV-seropositive patients were equally infectious, regardless of the pattern of disease (primary vs postprimary). Even though pulmonary tuberculosis in an HIV-seropositive adult probably results from reactivation of dormant foci or reinfection, the pattern on the chest roentgenogram often suggests primary disease, especially if the patient has AIDS.     

Interleukin-2 accelerates CD4 cell reconstitution in HIV-infected patients with severe immunosuppression despite highly active antiretroviral therapy: the ILSTIM study--ANRS 082

BACKGROUND: Despite effective highly active antiretroviral therapy (HAART), some patients infected with HIV have persistently low CD4 cell counts with risk of HIV disease progression. The addition of interleukin-2, a cytokine that stimulates CD4 T lymphocyte helper cells, may benefit patients with discordant responses. METHODS: A total of 72 HIV-infected patients with CD4 cell counts of 25-200 x 10(6) cells/l (median 145) and plasma HIV RNA < 1000 copies/ml were randomized in a multicentre study to receive open-label 4.5 x 10(6) IU interleukin-2 subcutaneously twice daily for 5 days every 6 weeks plus their ongoing HAART or were maintained on HAART alone (control group). After 24 weeks, all patients received interleukin-2 therapy plus HAART up to week 80. Primary end-point was the CD4 T cell area under the curve minus baseline up to week 24. RESULTS: After four cycles of interleukin-2, in an intent-to-treat analysis, the respective median CD4 cell area under the curve minus baseline values were +51 and +11 cells in the interleukin-2 (n = 34) and the control group (n = 36) (P < 0.0001). The percentage of patients in the two groups with CD4 cell counts > 200 x 10(6) cells/l was 81% and 33%, respectively (P < 0.0001). At week 80, the median CD4 cell counts in the two groups were 380 and 270 x 10(6) cells/l, respectively. Interleukin-2 treatment was reasonably well tolerated and did not result in sustained increases in plasma HIV RNA levels. CONCLUSIONS: Administration of interleukin-2 produces significant and sustained increase in CD4 cell counts in HAART-treated patients with persistent CD4 cell counts < 200 x 10(6) cells/l.     

Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa

BACKGROUND: A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. METHODS: Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count < 200 x 10 cells/l. The programme used standardized protocols (using generic medicines whenever possible), a team-approach to clinical care and a patient-centred approach to promote adherence. RESULTS: Two-hundred and eighty-seven adults naive to prior ART were followed for a median duration of 13.9 months. The median CD4 lymphocyte count was 43 x 10 cells/l at initiation of treatment, and the mean log10 HIV RNA was 5.18 copies/ml. The HIV RNA level was undetectable (< 400 copies/ml) in 88.1, 89.2, 84.2, 75.0 and 69.7% of patients at 3, 6, 12, 18 and 24 months respectively. The cumulative probability of remaining alive was 86.3% at 24 months on treatment for all patients, 91.4% for those with a baseline CD4 lymphocyte count > or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. CONCLUSIONS: ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.     

Survival in a cohort of human immunodeficiency virus-infected tuberculosis patients in New York City. Implications for the expansion of the AIDS case definition.

BACKGROUND. The occurrence of pulmonary tuberculosis in human immunodeficiency virus (HIV)-infected persons is believed to represent a less severe stage of HIV-related disease with a more favorable prognosis than other acquired immunodeficiency syndrome (AIDS)-defining conditions; therefore, it has been excluded from the AIDS definition established by the Centers for Disease Control (Atlanta, Ga) criteria. METHODS. To determine the prognosis of patients with HIV-related tuberculosis, we assessed the clinical, immunologic, and HIV infection status of a cohort of male subjects aged 20 to 44 years who were hospitalized with tuberculosis but without AIDS in New York City hospitals from 1985 through 1986, and we determined their mortality through May 1991. RESULTS. The 58 patients who agreed to participate were largely (90%) nonwhite and had a high prevalence of pulmonary tuberculosis (90%) and HIV infection (53%). Patients who were HIV seropositive had significantly lower CD4 cell counts (median, 0.136 x 10(9)/L; range, 0.013 x 10(9) to 2.314 x 10(9)/L vs median, 0.765 x 10(9)/L; range, 0.284 x 10(9) to 2.333 x 10(9)/L), and, during the follow-up period, an 83% mortality rate that was 7.5 times higher than the 11% rate in seronegative subjects. Survival analyses revealed that for all HIV-seropositive subjects the probability of death at 30 months was 72% and the median survival was 21 months (95% confidence interval, 15.5 to 26.5 months), while for HIV-seropositive subjects with CD4 cell counts of 0.2 x 10(9)/L or less, the probability of death at 30 months was 92% and the median survival was 15.75 months (95% confidence interval, 14.0 to 17.6 months). CONCLUSION. The prognosis for patients with HIV-related pulmonary tuberculosis is poor, and those with CD4 cell counts of 0.2 x 10(9)/L or less have survival patterns similar to that of patients with AIDS. We believe that these data support the expansion of the AIDS case definition to include persons with both pulmonary tuberculosis and severe HIV-related immunosuppression.     

Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda

BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active tuberculosis accelerates the progression of HIV infection. The validity of these findings has been questioned because of their retrospective design, diverse study populations, variable compliance with anti-tuberculous therapy and use of anti-retroviral medication. To assess the impact of tuberculosis on survival in HIV infection we performed a prospective study among HIV-infected Ugandan adults with and without tuberculosis. METHODS: In a prospective cohort study, 230 patients with HIV-associated tuberculosis and 442 HIV-infected subjects without tuberculosis were followed for a mean duration of 19 months for survival. To assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and controls were selected and matched according to baseline CD4 lymphocyte count, age, sex and tuberculin skin test status. RESULTS: During the follow-up period, 63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442 controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI), 1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x 10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1-year survival proportion was slightly lower in the cases than in the controls (0.91 versus 0.96), but by 2 years the survival proportion was significantly lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer, the survival proportion at 1 year for the controls was lower than cases (0.59 versus 0.64), but this difference was not statistically significant (P = 0.53; logrank test). After adjusting for age, sex, tuberculin skin test status, CD4 lymphocyte count, and history of HIV-related infections, the overall relative hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62-5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI, 0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer. CONCLUSION: The findings from this prospective study indicate that active tuberculosis exerts its greatest effect on survival in the early stages of HIV infection, when there is a reserve capacity of the host immune response. These observations provide a theoretical basis for the treatment of latent tuberculous infection in HIV-infected persons.     

Tuberculosis-associated severe CD4+ T-lymphocytopenia in HIV-seronegative patients from Dakar. SIDAK Research Group

OBJECTIVES: To determine the frequency and associated features of severe CD4+ T-lymphocytopenia (<300 cells/mm(3)) in HIV-seronegative patients with tuberculosis. METHODS: Statistical analysis of 430 consecutively enrolled HIV-seronegative inpatients with tuberculosis in two teaching hospitals in Dakar, Senegal. RESULTS: The mean CD4 + cell count was 602+/-318.3 cells/mm(3). CD4 + cell counts were below 300 cells/mm(3)in 62 patients (14.4%). Patients with fewer than 300 CD4+ cells/mm(3)differed from those with higher counts in being less likely to have a positive smear for acid-fast bacilli; in having a higher frequency of extrapulmonary involvement (pleural effusion, adenopathy and miliary disease) and oral candidiasis; and in having smaller tuberculin reactions, lower haemoglobin levels, less cavitation and less patchy infiltration. After adjustment for gender and age, all differences remained except miliary disease. CONCLUSIONS: A substantial percentage (14.4%) of HIV-seronegative hospitalized patients for tuberculosis in a West African country presented with severe CD4 + T-lymphocyte depletion and had clinical and radiographic features indicative of more advanced disease and accompanying immunodepression. These results and those already published suggest that tuberculosis should be regarded as one of the diseases associated with a subgroup of patients with "idiopathic CD4 + T-lymphocytopenia".     

Plasma cytomegalovirus DNA, pp65 antigenaemia and a low CD4 cell count remain risk factors for cytomegalovirus disease in patients receiving highly active antiretroviral therapy

OBJECTIVE: To study the natural history and the current risk factors for cytomegalovirus (CMV) disease in the context of highly active antiretroviral therapy (HAART). SETTING: Prospective multicentre cohort in 15 university hospitals in France. METHODS: A group of 198 patients with CD4 cell count < 100 x 10(6) cells/l (or < 200 x 10(6) cells/l under HAART for at least 2 months), no previous CMV disease and CMV-positive serology were followed every 4 months clinically and for virological testing including HIV RNA and CMV blood markers (culture, pp65 antigenaemia, plasma CMV DNA and CMV late mRNA by the polymerase chain reaction). RESULTS: At inclusion, median CD4 was 77 x 10(6) cells/l (0-308) and 85% of the patients received protease inhibitors. The percentage of patients receiving HAART reached 99% at 12 months. After a follow-up of 23.6 months, the incidence of CMV disease was 3.2/100 patient-years [95% confidence interval (CI) 1.3-5.0]. In univariate Cox models, all the CMV markers, a CD4 cell count remaining < 75 x 10(6) cells/l and an HIV viral load > 100,000 copies/ml were predictive for CMV disease. The hazard ratios for CMV disease were 11 for blood culture; 14 and 70 for pp65 antigenaemia of > or = 1 and > or = 100 nuclei/200,000 cells, respectively; 35 for plasma CMV DNA; 6 for CMV mRNA; 29 for CD4 < 75 x 10(6) cells/l; and 12 for HIV RNA > 100,000 copies/ml. In a stepwise multivariate analysis, only three covariates were independently associated with the occurrence of a disease: plasma CMV DNA, pp65 antigenaemia > or = 100 nuclei/200,000 cells and a CD4 count < 75 x 10(6) cells/l. CONCLUSION: CMV blood markers and CD4 count < 75 x 10(6) cells/l remain risk factors for CMV disease in patients receiving HAART. Analysis of plasma CMV DNA by the polymerase chain reaction is a reproducible and standardized tool that could be used as a decision marker for initiating CMV pre-emptive therapy.     

Impact of human immunodeficiency virus type 1 on tuberculosis in rural Haiti

We conducted a case-control study to determine the relative and attributable risk of HIV seropositivity for bacillary-positive (smear and/or culture) pulmonary tuberculosis in Haiti. There were 274 patients with tuberculosis and an equal number of control subjects. Antibodies to HIV were present in 67 (24%) patients and eight (3%) control subjects. Odds ratios suggested that the risk of pulmonary tuberculosis was 15.7 times as great (95% confidence interval, 4.8 to 5.0; p less than 0.05) in patients 20 to 39 yr of age who were HIV-seropositive than in HIV-seronegative patients. In contrast, the relative risk in those 40 to 59 yr of age was elevated (3.0 times), though not significantly (lower 95% confidence interval, 0.8). In the 20- to 39-yr age group, 31% of tuberculosis was attributable to HIV infection (95% confidence interval between 23 and 39%). HIV-seropositive and HIV-seronegative patients did not differ with respect to sputum smear positivity. HIV-seronegative patients were twice as likely to be infected with resistant organisms, though this was not significant. We conclude that HIV infection is a major risk factor for pulmonary tuberculosis in young adult residents of Haiti. This, together with the fact that similar proportions of HIV-seropositive and HIV-seronegative patients were potentially infectious, suggests that without vigorous counteraction tuberculosis will become a greater problem for Haiti.     

Reduction of IFN-gamma and IL-2 production by peripheral lymphocytes of HIV-exposed seronegative subjects.

OBJECTIVES: In order to evaluate the role played by cytokine profile as a co-factor involved in the resistance to HIV infection in couples serodiscordant for HIV, we studied HIV-seronegative subjects with multiple unprotected sexual exposures. DESIGN AND METHODS: Twenty-one HIV-exposed seronegative subjects (HEPS), their 21 HIV-seropositive partners and 10 HIV-seronegative unexposed individuals were studied for T helper (Th) types 1-2 cell pattern and CCR5 receptor. RESULTS: Twelve out of 21 HIV-seropositive partners of HEPS showed a CD4 cell count below 200 lymphocytes/microl. HIV strains were isolated from peripheral blood mononuclear cells (PBMC) in 17 patients (81%): seven subjects with syncytium-inducing strains and 10 with non-syncytium-inducing isolates. Low Th1 cytokine production and high levels of IL-4 were detected in HIV-seropositive subjects. A significant reduction of IL-2 and IFN-gamma expression in the CD4 and CD8 cells of HEPS was found compared with HIV-seronegative unexposed individuals. Similar levels of low IL-4 were present in both HEPS and controls. The partial deletion of a single allele (wild type/delta32) of CCR5 was found in only one HEPS. CONCLUSION: The downregulated Th1 profile we observed in HEPS could be related to a cellular anergy state with a protective role in the transmission rate of HIV. Low levels of IL-2 and IFN-gamma could be involved in a low-grade activation state of CD4 lymphocytes. A decrease of IFN-gamma levels could render macrophage cells incapable of antigen presentation, thus resulting in a reduction of the cell-to-cell spread of infection.     

Correlation between CD4 cell counts and cellular and plasma viral load in HIV-1-seropositive individuals.

We conducted a study of 152 HIV-1-seropositive individuals in order to evaluate the possible correlations between the isolation of HIV from peripheral blood mononuclear cells or from plasma and CD4 cell counts. HIV was isolated from only 36% of plasma samples, and the isolation rate was closely related to CD4 cell counts, increasing gradually from 0% in subjects with greater than 800 x 10(6)/l CD4 cells to 88% in those with less than 100 x 10(6)/l CD4 cells. In contrast, HIV was isolated from 92% of cell samples (99% in subjects with less than 900 x 10(6)/l CD4 cells, 46% in those with CD4 counts greater than or equal to 900 x 10(6)/l). Since most cell samples were positive, a scoring method was designed to quantify the cellular viral load. The results obtained demonstrated that the cellular viral load was closely related to CD4 counts. We also found that the cellular viral load was higher in subjects with either positive plasma isolation or positive p24 antigenaemia. The measurement of the cellular viral load by this scoring method appears to be useful for the management of HIV-seropositive individuals and for the evaluation of therapeutic trials.     

Detection of opportunistic and non-opportunistic intestinal parasites and liver flukes in HIV-positive and HIV-negative subjects

We assessed the frequency and distribution of infection with opportunistic and non-opportunistic intestinal parasites and the liver fluke, Opisthorchis viverrini, in HIV-seropositive and HIV-seronegative subjects. Age- and sex-matched HIV-seropositive (n = 78) and HIV-seronegative patients (n = 78) from two hospitals in Khon Kaen Province, Thailand, participated in this study from November 1998 to August 2000. These subjects were divided according to the presence of diarrhea and CD4 counts. A single stool sample was obtained and analyzed by using specific techniques. Opisthorchis viverrini, was the most common parasite (19.2%) in each group. The prevalence rates of Cryptosporidium spp (11.5%) and Strongyloides stercoralis (17.9%) in the HIV-seropositive group were significantly (p < 0.05) higher than those in the HIV-seronegative group (1.0% for Cryptosporidium spp and 7.7% for S. stercoralis infections). The prevalences of these two parasites were 28% for Cryptosporidium spp and 20% for S. stercoralis in HIV-seropositives with diarrhea and CD4 counts lower than 100 cells/mm3, and were higher compared with patients without diarrhea or with high CD4 counts. These results suggest that infection with these parasites increases during HIV infection. The epidemiological distribution of Cryptosporidium and S. stercoralis may have implications for AIDS-related diseases.     

Low HIV-1 proviral DNA burden detected by negative polymerase chain reaction in seropositive individuals correlates with slower disease progression.

During 1989, 316 members of a cohort of homosexual men were tested for HIV-specific DNA by the polymerase chain reaction (PCR) using a pair of gag-region primers. Of 125 HIV-seronegative subjects, 123 (98.4%) were PCR-negative while 158 (82.7%) of 191 HIV-seropositive subjects were PCR-positive. Fewer of the 33 subjects who were seropositive and PCR-negative were at Centers for Disease Control (CDC) stage IV than the seropositive, PCR-positive subjects (6 versus 25%; P = 0.030). The seropositive, PCR-negative group had higher mean CD4 counts (640 versus 490 x 10(6) cells/l; P = 0.006), higher CD4: CD8 ratios (0.92 versus 0.64; P = 0.004), lower immunoglobulin (Ig) G levels (1290 versus 1645 mg/dl; P = 0.002), lower IgA levels (168 versus 251 mg/dl; P less than 0.001), and lower C1q binding activity (8 versus 14%; P = 0.010) than the seropositive, PCR-positive subjects. The median rate of CD4 cell decline in the 3 years preceding the PCR sample was less marked in the seropositive, PCR-negative group than the seropositive, PCR-positive group (-58 versus -77 x 10(6) cells/l per year; P = 0.028). To control for duration of infection, we restricted the analysis to the subgroups of 11 seropositive, PCR-negative subjects and 34 seropositive, PCR-positive subjects who had seroconverted earlier in the cohort study. Both subgroups had similar durations of infection, yet the same pattern of differences persisted.(ABSTRACT TRUNCATED AT 250 WORDS)     

CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy

OBJECTIVE: To evaluate the safety of treatment interruption guided by CD4+ cell count in HIV-infected patients followed up prospectively. METHODS: Patients on highly active antiretroviral therapy with CD4+ cell counts > 500 x 10(6) cells/l discontinued therapy with instructions to start therapy again before their CD4+ count dropped below 200 x 10(6) cells/l. Any patients who resumed therapy would be eligible to interrupt treatment again once their CD4+ cell count increased above 500 x 10(6) cells/l. RESULTS: Data on 71 HIV infected patients is reported. Their median nadir CD4+ cell count before antiretroviral treatment was 352 x 10(6) cells/l [interquartile range (IQR), 294-445 x 10(6) cells/l]. The median CD4+ cell count at the time of first interruption was 790 x 10(6) cells/l (IQR, 657-1041 x 10(6) cells/l). The median follow-up after starting the first treatment interruption was 28.3 months (IQR, 21.4-37.0 months). During the follow-up 49 patients restarted therapy and 22 patients remain off therapy; 24 patients have interrupted therapy twice, nine patients have interrupted therapy three times and six patients four times. No AIDS-defining illnesses occurred during the follow-up. The median duration of the first interruption was 15 months (IQR, 6-26 months). The overall reduction of time on therapy was 71.1%. The duration of the first interruption and the reduction of time on therapy were related to nadir CD4+ cell count. The patients who resumed HAART rapidly regained CD4+ cells and achieved viral suppression. CONCLUSION: If carefully monitored, treatment interruptions guided by CD4+ cell count in patients with an initially high CD4+ cell counts are clinically safe, decrease exposure to the drugs and do not reduce the efficacy of therapy when this is re-started.