Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: implications for when to initiate therapy

BACKGROUND: The optimal time to initiate highly active antiretroviral therapy (HAART) remains unclear. METHODS: Five hundred eighty-three human immunodeficiency virus (HIV)-seropositive and 920 HIV-seronegative injection drug users (IDUs) were followed from 1997 to 2000. HIV-seropositive participants were categorized according to receipt of HAART (either initiated or switched to HAART) and initial CD4 cell count. Survival analysis that included delayed-entry and Cox proportional-hazards models was used to evaluate the effect of HAART, with adjustments for factors associated with access to HAART. RESULTS: Compared with HIV-seronegative participants, overall survival was similar in HIV-seropositive participants who received HAART at >350 CD4 cells/microL, but mortality was higher both in participants with >350 CD4 cells/microL who did not receive HAART and in participants who received HAART at 200-350 CD4 cells/microL (mortality rates, 19.9, 24.0, 43.0, and 50.5/1000 person-years, respectively). In proportional-hazards models in which HIV-seronegative participants were the reference group and in which age, sex, race, frequency of drug use, substance-abuse treatment, and health-care utilization were adjusted for, hazard ratios were 1.01 (95% confidence interval [CI], 0.41-2.45), 2.28 (95% CI, 1.38-3.78), and 2.09 (95% CI, 1.07-4.10) for the latter 3 groups. In HIV-seropositive participants, HAART significantly improved survival when initiated at CD4 cell counts < 200 cells/microL. CONCLUSIONS: Survival of HIV-seropositive participants receiving HAART approximated that of HIV-seronegative participants only when therapy was given at CD4 cell counts > 350 cells/microL. These data, restricted to IDUs, suggest initiating or switching to HAART at higher CD4 cell levels than are currently recommended.     

DISCORDANCE BETWEEN BODY MASS INDEX AND ANTHROPOMETRIC MEASUREMENTS AMONG HIV-1-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY AND WITH LIPOATROPHY/LIPOHYPERTROPHY SYNDROME

Introduction:

Highly Active Antiretroviral Therapy (HAART) has improved and extended the lives of thousands of people living with HIV/AIDS around the world. However, this treatment can lead to the development of adverse reactions such as lipoatrophy/lipohypertrophy syndrome (LLS) and its associated risks.

Objective:

This study was designed to assess the prevalence of self-reported lipodystrophy and nutritional status by anthropometric measurements in patients with HIV/AIDS.

Methods:

An observational study of 227 adult patients in the Secondary Immunodeficiencies Outpatient Department of Dermatology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo (3002 ADEE-HCFMUSP). The sample was divided into three groups; Group 1 = 92 patients on HAART and with self-reported lipodystrophy, Group 2 = 70 patients on HAART without self-reported lipodystrophy and Group 3 = 65 patients not taking HAART. The nutritional status of individuals in the study sample was determined by body mass index (BMI) and percentage of body fat (% BF). The cardiovascular risk and diseases associated with abdominal obesity were determined by waist/hip ratio (WHR) and waist circumference (WC).

Results:

The prevalence of self-reported lipoatrophy/lipohypertrophy syndrome was 33% among women and 59% among men. Anthropometry showed depletion of fat mass in the evaluation of the triceps (TSF) in the treatment groups with HAART and was statistically independent of gender; for men p = 0.001, and for women p = 0.007. Similar results were found in the measurement of skin folds of the upper and lower body (p = 0.001 and p = 0.003 respectively). In assessing the nutritional status of groups by BMI and % BF, excess weight and body fat were more prevalent among women compared to men (p = 0.726). The WHR and WC revealed risks for cardiovascular and other diseases associated with abdominal obesity for women on HAART and with self-reported LLS (p = 0.005) and (p = 0.011).

Conclusions:

Anthropometric measurements were useful in the confirmation of the prevalence of LLS. BMI alone does not appear to be a good parameter for assessing the nutritional status of HIV-infected patients on HAART and with LLS. Other anthropometric measurements are needed to evaluate patients with the lipoatrophy/lipohypertrophy syndrome.     

Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women

We examined incidence and correlates of progression and regression of abnormal cervical cytologic test results, defined as at least low-grade squamous intraepithelial lesions (SILs), in 774 human immunodeficiency virus (HIV)-seropositive and 391 HIV-seronegative women monitored semiannually for up to 5.5 years. During follow-up, 224 (35%) HIV-seropositive women and 34 (9%) HIV-seronegative women had incident SILs detected by Pap test; 47 (7%) HIV-seropositive women developed high-grade lesions. The incidence of SILs was 11.5 cases among HIV-seropositive and 2.6 cases among HIV-seronegative women per 100 person-years of observation (rate ratio, 4.5; 95% confidence interval, 3.1-6.4; P<.001). Risk of incident SILs and likelihood of Pap test progression were increased among HIV-seropositive women with CD4(+) lymphocyte counts <500 cells/mm(3) and among women with human papillomavirus (HPV) infection, with risk-ordering from low- to high-risk HPV type. SIL regression was less likely among HIV-seropositive women with higher HIV loads. No beneficial effect of highly active antiretroviral therapy was demonstrated.     

Attitudes toward HIV treatments influence unsafe sexual and injection practices among injecting drug users

OBJECTIVE: To determine if HIV treatment-related attitudes are associated with unprotected sex and needle sharing among HIV-seropositive and -seronegative injecting drug users (IDU) in Baltimore, Maryland. DESIGN AND METHODS: IDU participating in a cohort study seen between December 2000 and July 2001 completed an interviewer-administered questionnaire on attitudes toward HIV treatment and risk behaviors (593 HIV-seronegative, 338 HIV-seropositive), including: perceived HIV transmissibility through unprotected sex and needle sharing, and safer sex and injection fatigue. Logistic regression was used to examine the role of attitudinal factors on needle sharing and unsafe sex. RESULTS: Almost two-thirds of sexually active participants engaged in unprotected sex and approximately half of those injecting drugs shared needles. Among HIV-seropositive IDU, perception of reduced HIV transmissibility through unprotected sex was significantly associated with unprotected sex [adjusted odds ratio (AOR), 3.33; 95% confidence interval (CI), 1.05-10.55). Safer injection fatigue was independently associated with needle sharing among HIV-seropositive IDU (AOR, 6.55; 95% CI, 1.69-25.39). Among HIV-seronegative IDU, safer sex fatigue and safer injection fatigue were independently associated with unprotected sex (AOR, 3.12; 95% CI, 1.17-8.35) and needle sharing (AOR, 5.15; 95% CI, 2.33-11.37), respectively. CONCLUSION: Among HIV-seropositive IDU, perceiving that HIV treatments reduce HIV transmission was significantly associated with unprotected sex. Risk reduction fatigue was strongly associated with unsafe sexual and injection behaviors among HIV-seronegative individuals. HIV prevention interventions must consider the unintended impact of HIV treatments on attitudes and risk behaviors among IDU.     

Association of human immunodeficiency virus and anal human papillomavirus infection among homosexual men.

BACKGROUND--A previous study of men with proctitis, proctocolitis, or enteritis showed an association of anal human papillomavirus (HPV) infection with human immunodeficiency virus (HIV) infection. Because anorectal abnormalities may confound an observed association between anal HPV DNA and HIV seropositivity, the present study was undertaken among consecutive homosexual men seeking HIV serologic testing who were unselected for anorectal symptoms. METHODS--Consecutive homosexual men underwent a standardized interview, physical examination, and collection of specimens for HIV serologic testing and detection of anal HPV DNA. RESULTS--Anal HPV DNA was detected in eight (31%) of 26 HIV-seropositive men and in 10 (8%) of 119 HIV-seronegative men (odds ratio, 5.8; 95% confidence interval, 1.1 to 30.1, adjusted for history of sexually transmitted disease, current anorectal symptoms, and age). When men with anorectal symptoms were excluded from the analysis, anal HPV DNA was detected in 27% of seropositive men compared with 8% of seronegative men (odds ratio, 4.4; 95% confidence interval, 1.4 to 13.4). There was no difference between HIV-seropositive and HIV-seronegative men with respect to distribution of type of HPV DNA. Men with group II or III and group IV HIV disease were 4.1 and 10.9 times, respectively, more likely than HIV-seronegative men to have anal HPV DNA detected. CONCLUSIONS--Because HIV-seropositive men appear to be at increased risk for the detection of anal HPV DNA, the natural course of anal HPV infection should be compared among HIV-seropositive and HIV-seronegative homosexual men.     

Population-based study of malignancies and HIV infection among injecting drug users in a New York City methadone treatment program, 1985-1991.

OBJECTIVE: To study the incidence of AIDS-defining and non-AIDS-defining malignancies in injecting drug users with and without HIV infection in a methadone maintenance treatment program (MMTP). DESIGN: Prospective study within a hospital-affiliated MMTP with on-site primary medical services. The MMTP has been the site of a voluntary longitudinal cohort study of HIV infection since 1985. METHODS: Active surveillance for all new cancer cases occurring among patients in the MMTP between July 1985 and August 1991. Cancer cases were identified by review of clinic and hospital records, hospital-based tumor registries, and New York City vital records. Cancer incidence was determined for the overall MMTP population and for HIV-seropositive and HIV-seronegative cohort study subgroups. RESULTS: During the study period the MMTP population comprised 2174 patients followed for 5491 person-years; 844 patients (380 HIV-seropositive, 464 HIV-seronegative) also participated in the cohort study. Fifteen non-AIDS-defining malignancies occurred among all MMTP patients (2.73 cases per 1000 person-years); the most frequent sites were lung, larynx, and cervix (n = 6, 2 and 2, respectively). Eighty per cent of patients with these cancer diagnoses and known HIV serologic status were seropositive. Within the cohort study group, six out of 380 HIV-seropositives developed non-AIDS-defining cancers versus one out of 464 HIV-seronegatives (P = 0.05, Fisher's exact test). Lung cancer cases in HIV-seropositive patients tended to occur at an earlier age and was more aggressive than in patients with HIV-seronegative or unknown status. During the same period, two cases of AIDS-defining lymphoma and one case of Kaposi's sarcoma were diagnosed in the MMTP population (0.5 cases per 1000 person-years). CONCLUSION: Solid neoplasms, while infrequent, were associated with HIV infection and were more common than AIDS-defining cancers in this population of drug injectors. Further study is needed to explore the relationship between HIV, behavioral factors, and cancer risk in injecting drug users.     

Cryptogenic liver disease in HIV-seropositive men

Objectives In the era of highly active antiretroviral therapy (HAART), liver disease has become a leading cause of morbidity and mortality in HIV-seropositive individuals. Although liver disease is commonly caused by viral co-infection, it has also been described in patients without viral hepatitis. In this study, we determined clinical factors associated with the development of cryptogenic liver disease in HIV-infected individuals.
Methods HIV-seropositive and -seronegative patients undergoing evaluation for liver transplantation were selected if they met clinical criteria for cryptogenic liver disease. Clinical data were collected retrospectively, and radiological and histological data were reviewed separately.
Results Nine HIV-seropositive individuals were compared with 41 HIV-seronegative patients with cryptogenic liver disease. Only one HIV-seropositive patient (11%) had cirrhosis, compared to 39 HIV-seronegative patients (93%) ( P <0.001). Three HIV-infected patients (33%) had histological evidence of nodular regenerative hyperplasia. HIV-seropositive patients had significantly lower body mass indices, and lower Child–Pugh–Turcotte and Model for Endstage Liver Disease scores than HIV-seronegative patients ( P <0.05).
Conclusions Advanced cryptogenic liver disease in HIV-infected patients is infrequently caused by cirrhosis, and more frequently by nodular regenerative hyperplasia. This disease entity may become more common in the HAART era, and may contribute to an increased morbidity in HIV-infected individuals.     

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.     

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)     

Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study

BACKGROUND: The risk of diabetes mellitus (DM) in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) has not been well defined. METHODS: We conducted an analysis in the Multicenter AIDS Cohort Study to determine the prevalence and incidence of DM in this cohort of HIV-infected and HIV-seronegative men. Prevalence analysis included 1278 men (710 HIV seronegative and 568 HIV infected, 411 receiving HAART) with fasting glucose concentration determinations at baseline. Incidence analysis included 680 of these 1278 men who at the baseline visit had a fasting glucose concentration of 98 mg/dL (5.4 mmol/L) or less, no self-reported history of DM, and no self-reported use of antidiabetic medication. Diabetes mellitus was defined as a fasting glucose concentration of 126 mg/dL (7 mmol/L) or higher, self-reported diagnosis of DM, or self-reported use of antidiabetic medication. RESULTS: Fifty-seven (14%) of the 411 HIV-infected men using HAART at the baseline visit had prevalent DM compared with 33 (5%) of the 711 HIV-seronegative men (prevalence ratio = 4.6; 95% confidence interval, 3.0-7.1, adjusted for age and body mass index [calculated as weight in kilograms divided by the square of height in meters]). The rate of incident DM was 4.7 cases per 100 person-years among HIV-infected men using HAART compared with 1.4 cases per 100 person-years among HIV-seronegative men (rate ratio = 4.11; 95% confidence interval, 1.85-9.16, adjusted for age and body mass index), during the 4-year observation period, based on a median follow-up of 2.3 years. CONCLUSION: The incidence of DM in HIV-infected men with HAART exposure was greater than 4 times that of HIV-seronegative men, representing a risk that is higher than previous estimates.     

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.     

HIV infection in patients with tuberculosis in Kinshasa, Zaire

To better define the interrelationship of infection with human immunodeficiency virus (HIV) and tuberculosis (TB), we conducted three HIV serosurveys of inpatients and outpatients with confirmed or suspected TB in Kinshasa, Zaire. HIV seroprevalence in hospitalized sanatorium patients did not change significantly in serosurveys conducted in 1985 and 1987 (92/231 [40%] versus 85/234 [36%]). These proportions were significantly higher than the 17% HIV seroprevalence observed in a 1987 serosurvey of 509 consecutive patients with an initial diagnosis of pulmonary TB seen at an outpatient TB diagnostic center in Kinshasa (p less than 0.001). HIV seroprevalence was higher in sanatorium patients with extrapulmonary TB (22/46 [48%]) and suspected pulmonary TB (60/132 [45%]) than in patients with bacteriologically confirmed pulmonary TB (94/287 [33%]) (p less than 0.02). Mycobacterium sputum isolation rates were similar in HIV-seropositive (28/34 [82%]) and HIV-seronegative patients (135/159 [85%]). All isolates were Mycobacterium tuberculosis. Eighteen (21%) of 84 HIV-seropositive sanatorium patients in 1987, who were followed for two months after admission, had died, compared with 11 (9%) of 128 HIV-seronegative patients (p less than 0.01). However, clearance rates of acid-fast bacilli from sputum after standard therapy were equally good in HIV-seropositive and HIV-seronegative survivors. With the growing AIDS problem, the serious TB burden in sub-Saharan Africa may become even more onerous and may critically overload the stressed African health care systems.     

The effect of immunodeficiency on cutaneous delayed-type hypersensitivity testing in HIV-infected women without anergy: implications for tuberculin testing. HER Study Group. HIV Epidemiology Research.

SETTING: A collaborative study in four urban medical centers in the United States. OBJECTIVE: To determine the effect of human immunodeficiency virus (HIV) infection and immunodeficiency on delayed type hypersensitivity (DTH) responses and the implications for interpretation of tuberculin reactions in non-anergic women with or at risk for HIV infection. DESIGN: Demographic and behavioral information, HIV antibody testing, CD4+ lymphocyte counts, and cutaneous responses to DTH testing with mumps, Candida, tetanus toxoid, and tuberculin (purified protein derivative-PPD) antigens were obtained in 1184 women. RESULTS: Reactions to one or more of the four antigens occurred in 436 HIV-seropositive and 356 high-risk seronegative women. Among non-anergic women, HIV-seropositives were less likely (P < or = 0.05) to react to mumps (62% vs 81%), tetanus (72% vs 84%), and PPD (13% vs 19%). Induration in HIV-seropositive reactors was associated with CD4+ cell level for mumps (P = 0.004) and tetanus (P < 0.001), but not for Candida or PPD. HIV-seropositive reactors with CD4+ cell counts >500/mm3 did not have significantly smaller reactions than HIV-seronegatives for any antigen tested. PPD sizes were similar among HIV-seropositive reactors with CD4+ cell counts >500/mm3 (12.4 +/- 7.4 mm) and HIV-seronegative reactors (12.0 +/- 8.3 mm); induration > or =10 mm was seen in 16/173 (9.2%) seropositive women with CD4+ cell counts >500/mm3 and 41/356 (11.5%) seronegative women, respectively (P = 0.5). CONCLUSION: Among HIV-infected women able to react to a DTH antigen, induration in response to that antigen was relatively intact at CD4+ counts >500/mm3. This suggests that degree of immunodeficiency should be considered when interpreting PPD reactions in HIV-infected persons.     

Pulmonary tuberculosis in Kigali, Rwanda. Impact of human immunodeficiency virus infection on clinical and radiographic presentation.

The aim of the present study was to compare the clinical and radiographic presentation as well as the therapeutic outcome of pulmonary tuberculosis (PT) in adult patients with and without human immunodeficiency virus type 1 (HIV-1) infection in Kigali, Rwanda. Over a 17-month period 59 consecutive patients with bacteriologically and/or histopathologically documented PT were enrolled. Of these, 48 (81%) patients were HIV seropositive. Among these, 35 fit the WHO clinical criteria for AIDS (WHOCCA) at the time of admission. Significant differences were found between the HIV-seropositive and HIV-seronegative groups of patients: fever (85 versus 36%; p less than 0.001), tuberculin skin test anergy (69 versus 0%; p less than 0.01), mediastinal and/or hilar adenopathies (31 versus 0%; p = 0.05), and pleural effusion (43 versus 9%; p less than 0.05) were more frequently encountered in the HIV-seropositive group, and upper lobe infiltrates (55 versus 16%; p less than 0.02) and cavitation (91 versus 39%; p less than 0.003) were more often seen in the HIV-seronegative group. However, HIV-seropositive patients not meeting WHOCCA were less frequently anergic (0 versus 100%; p less than 0.001) and feverish (53 versus 97%; p less than 0.01) and more often had cavitation (69 versus 28%; p less than 0.02) and less often mediastinal and/or hilar adenopathies (7 versus 40%; p less than 0.04) compared with HIV-seropositive patients meeting WHOCCA. Under antituberculosis treatment, clearance of fever was slower in HIV-seropositive compared with HIV-seronegative patients, and among the HIV-seropositive group it was slower in those fitting WHOCCA.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of human immunodeficiency virus (HIV) infection on antibody responses to influenza vaccines

STUDY OBJECTIVE: To ascertain whether subjects infected with human immunodeficiency virus (HIV) generally develop protective hemagglutination inhibition antibody responses to inactivated influenza vaccines. DESIGN: Prospective study of 104 persons before and after immunization. SETTING: Outpatient clinic and hospital ward. PATIENTS: Persons with the acquired immunodeficiency syndrome (AIDS) (n = 25), AIDS-related complex (n = 14), and HIV-seropositive men with only lymphadenopathy or no symptoms (n = 27). Controls were HIV-seronegative homosexual men (n = 22) and HIV-seronegative heterosexuals (n = 16). INTERVENTIONS: Subjects were immunized with inactivated vaccines containing 15 micrograms of each of the following influenza virus hemagglutinins: A/Taiwan/1/86 (HINI), A/Mississippi/1/85 (H3N2), A/Chile/1/83 (HINI), and B/Ann Arbor/1/86. MEASUREMENTS AND MAIN RESULTS: Fourfold or greater antibody responses occurred less frequently in subjects with HIV infections than in HIV-seronegative controls. Protective levels (1:64 or greater) of hemagglutination inhibition antibodies were attained by 94% to 100% of HIV-seronegative controls, 52% to 89% of HIV-seropositive asymptomatic subjects, and 13% to 50% of subjects with AIDS or AIDS-related complex. No increase in the prevalence or level of serum HIV p24 antigen or clinical deterioration was detected among HIV-infected persons after influenza immunization. CONCLUSIONS: Because of the poor antibody responses to influenza vaccines among HIV-infected subjects, even in many with no or minimal symptoms, alternative strategies for preventing influenza, such as booster doses of influenza vaccine, prophylaxis with amantidine, or both should be considered.     

Bone mineral density is not reduced in HIV-infected Caucasian men treated with highly active antiretroviral therapy

OBJECTIVE: Recent studies have reported low bone mineral density (BMD) in patients infected with human immunodeficiency virus (HIV). Frequently these findings have been attributed to treatment with highly active antiretroviral therapy (HAART). We sought to determine whether BMD in HIV-infected men treated with HAART for at least 3 months is different from that in healthy controls, and, if so, what HIV-related factors might explain this finding. DESIGN: Cross-sectional analysis. PATIENTS: Fifty-nine HIV-infected Caucasian men treated with HAART, and 118 healthy community-dwelling controls. Each HIV-infected man was age-matched (within 5 years) to two controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters. RESULTS: The mean duration of known HIV infection was 8.5 years, and of treatment with HAART was 52 months. There was no significant difference in mean BMD between groups at the lumbar spine (HIV group: 1.23 g/cm2, controls: 1.25 g/cm2; P = 0.53) or total body (HIV group: 1.18 g/cm2, controls: 1.20 g/cm2; P = 0.09). At the total hip the HIV-infected group had significantly lower BMD than the control group (HIV group: 1.03 g/cm2, controls: 1.09 g/cm2; P = 0.01). The HIV-infected group were, on average, 6.3 kg lighter than the controls. After adjusting for this weight difference, HIV infection was not an independent predictor of BMD at any site (lumbar spine P = 0.79; total hip P = 0.18; total body P = 0.76). CONCLUSIONS: HIV-infected men treated with HAART are lighter than healthy controls. This weight difference is responsible for a small decrement in hip BMD. Overall, BMD is not significantly reduced in HIV-infected Caucasian men treated with HAART.     

Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers

BACKGROUND: Previous uncontrolled reports have suggested that HIV-seropositive persons develop an accelerated form of emphysema. OBJECTIVE: To characterize the risk for emphysema in a stable HIV-seropositive outpatient population. DESIGN: Controlled, cross-sectional analysis. SETTING: Midwestern urban community. PARTICIPANTS: HIV-seropositive persons (n = 114) without AIDS-related pulmonary complications and HIV-seronegative controls (n = 44), matched for age and smoking history. MEASUREMENTS: Measurement of pulmonary function, bronchoalveolar lavage, and high-resolution computed tomography of the chest. RESULTS: The incidence of emphysema was 15% (17 of 114) in the HIV-seropositive group compared with 2% (1 of 44) in the HIV-seronegative group (P = 0.025). The incidence of emphysema in participants with a smoking history of 12 pack-years or greater was 37% (14 of 38 persons) in the HIV-seropositive group compared with 0% (0 of 14 persons) in the HIV-seronegative group (P = 0.011). The percentage of cytotoxic lymphocytes in lavage fluid was much higher in HIV-seropositive smokers with emphysema. CONCLUSIONS: Infection with HIV accelerates the onset of smoking-induced emphysema. The results of this study support the emerging concept that cytotoxic lymphocytes may have an important role in emphysema pathogenesis.     

Herpes zoster in African patients: a clinical predictor of human immunodeficiency virus infection

A recent episode or a history of herpes zoster was found in 30 (11%) of 284 patients hospitalized with human immunodeficiency virus (HIV) infection at Mama Yemo Hospital, Kinshasa, Zaire. Of 146 African patients with a history of herpes zoster who were referred to us by physicians at the Mama Yemo Hospital, 133 (91%) were HIV seropositive. The clinical characteristics of the herpes zoster episodes did not differ between HIV-seropositive and -seronegative individuals, except that 23% of the HIV-seropositive patients experienced recurrences compared with none of the HIV-seronegative patients (P = .05). No patient developed a generalized herpes zoster eruption, and only patients with ophthalmic zoster developed related complications. Patients who experienced severe pain during their herpes zoster attack lost more weight than did those who had only minor pain (P = .0003).     

The polymorphisms in DC-SIGNR affect susceptibility to HIV type 1 infection

Dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN) and its homologue DC-SIGNR (DC-SIGN related) have been thought to play an important role in establishing HIV infection by enhancing trans-infection of CD4(+)T cells in the regional lymph nodes. To identify polymorphisms associated with HIV-exposed seronegative (ESN) individuals in Thais, genomic DNA from 102 HIV-seronegative individuals of HIV-seropositive spouses, 305 HIV-seropositive individuals, and 290 HIV-seronegative blood donors was genotyped for two single nucleotide polymorphisms (SNPs) in DC-SIGN promoter (-139A/G and 336A/G), a repeat number of 69 bp in Exon 4 of DC-SIGN and DC-SIGNR, and one SNP in Exon 5 of DC-SIGNR (rs2277998A/G). We found that the proportion of individuals possessing a heterozygous 7/5 and 9/5 repeat and A allele at rs2277998 of DC-SIGNR in HIV-seronegative individuals of HIV-seropositive spouses was significantly higher than HIV-seropositive individuals [p = 0.0373, OR (95% CI) = 0.57 (0.32,1.01); p = 0.0232, OR (95% CI) = 0.38 (0.15,0.98); and p = 0.0445, OR (95% CI) = 0.61 (0.37,1.02), respectively]. Analysis after stratifying by gender showed that these associations were observed only in females but not in males. Moreover, HIV-seropositive females tend to have a homozygous 7/7 repeat more frequently than HIV-seronegative females with a marginal level of significance [p = 0.0556, OR (95% CI) = 1.79 (0.94,3.40)]. Haplotype analysis showed that the proportion of individuals possessing the 5A haplotype in HIV-seronegative females was significantly higher than HIV-seropositive females [p = 0.0133, OR = 0.50 (0.27,0.90)]. These associations suggest that DC-SIGNR may affect susceptibility to HIV infection by a mechanism that is different in females and males. Further studies are warranted to investigate the mechanisms of their function.     

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.