Pilot evaluation of a second-generation electronic pill box for adherence to Bedaquiline and antiretroviral therapy in drug-resistant TB/HIV co-infected patients in KwaZulu-Natal, South Africa.

BACKGROUND: The introduction of Bedaquiline, the first new antimycobacterial drug in over 40 years, has highlighted the critical importance of medication adherence in drug-resistant tuberculosis (DR-TB) treatment to prevent amplified drug-resistance and derive sustained benefit. Real-time electronic dose monitoring (EDM) accurately measures adherence and allows for titration of adherence support for anti-retroviral therapy (ART). The goal of this study was to evaluate the accuracy and acceptability of a next-generation electronic pillbox (Wisepill RT2000) for Bedaquiline-containing TB regimens. METHODS: Eligible patients were DR-TB/HIV co-infected adults hospitalized for the initiation of Bedaquiline-containing treatment regimens in KwaZulu-Natal, South Africa. A one-way crossover design was used to evaluate levels of adherence and patient acceptance of EDM. Each patient was given a Wisepill device which was filled with ART, Levofloxacin or Bedaquiline over three consecutive weeks. Medication adherence was measured using Wisepill counts, patient-reported seven-day recall, and weekly pill count. An open-ended qualitative questionnaire at the end of the study evaluated participant acceptability of the Wisepill device. RESULTS: We enrolled 21 DR-TB/HIV co-infected inpatients admitted for the initiation of Bedaquiline from August through September 2016. In aggregate patients were similarly adherent to Bedaquiline (100%) compared to Levofloxacin (100%) and ART (98.9%) by pill count. Wisepill was more sensitive (100%) compared to seven-day recall (0%) in detecting non-adherence events (p = 0.02). Patients reported positive experiences with Wisepill and expressed willingness to use the device during a full course of DR-TB treatment. There were no concerns about stigma, confidentiality, or remote monitoring. CONCLUSION: In this pilot study patients were highly adherent to Bedaquiline by all adherence measures. However, there was lower adherence to ART by pill count and Wisepill suggesting a possible challenge for adherence with ART. The use of EDM identified significantly more missed doses than seven-day recall. Wisepill was highly acceptable to DR-TB/HIV patients in South Africa, and is a promising modality to support and monitor medication adherence in complex treatment regimens.

Impact of nurse-delivered community-based CD4 services on facilitating pre-ART care in rural South Africa.

BACKGROUND: HIV testing, diagnosis and treatment programs have expanded globally, particularly in resource-limited settings. Diagnosis must be followed by determination of treatment eligibility and referral to care prior to initiation of antiretroviral treatment (ART). However, barriers and delays along these early steps in the treatment cascade may impede successful ART initiation. New strategies are needed to facilitate the treatment cascade. We evaluated the role of on site CD4+ T cell count phlebotomy services by nurses in facilitating pre-ART care in a community-based voluntary counseling and testing program (CBVCT) in rural South Africa. METHODS: We retrospectively evaluated CBVCT services during five continuous time periods over three years: three periods when a nurse was present on site, and two periods when the nurse was absent. When a nurse was present, CD4 count phlebotomy was performed immediately after HIV testing to determine ART eligibility. When a nurse was absent, patients were referred to their local primary care clinic for CD4 testing. For each period, we determined the proportion of HIV-positive community members who completed CD4 testing, received notification of CD4 count results, as well as the time to test completion and result notification. RESULTS: Between 2010 and 2013, 7213 individuals accessed CBVCT services; of these, 620 (8.6 %) individuals were HIV-positive, 205 (33.1 %) were eligible for ART according to South African national CD4 count criteria, and 78 (38.0 % of those eligible) initiated ART. During the periods when a professional nurse was available to provide CD4 phlebotomy services, HIV-positive clients were significantly more likely to complete CD4 testing than during periods when these services were not available (85.5 % vs. 37.3 %, p < 0.001). Additionally, when nurses were present, individuals were significantly more likely to be notified of CD4 results (60.6 % vs. 26.7 %, p <0.001). The time from HIV screening to CD4 test completion was also significantly shorter during nurse presence than nurse absence (median 8 days (IQR 4-19) vs. 35 days (IQR 15-131), p < 0.001). CONCLUSIONS: These findings indicate that in addition to CBVCT, availability of on site CD4 phlebotomy may reduce loss along the pre-ART care cascade and facilitate timely entry into HIV care.

Transmission risk behaviour at enrolment in participants in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: A proportion of HIV-positive people have condomless sex. Antiretroviral treatment (ART) reduces infectiousness, but a substantial proportion of HIV-diagnosed people are not yet on ART. We describe baseline self-reported risk behaviours in ART-naïve Strategic Timing of AntiRetroviral Treatment (START) trial participants. METHODS: All START participants completed a risk behaviour questionnaire. Data were collected on sociodemographics, lifestyle factors, health and wellbeing status and clinical status. Recent sexual behaviour and HIV transmission beliefs in the context of ART were also assessed. The primary interest was in condomless sex with serodifferent partners (CLS-D) in the past two months. RESULTS: A total of 4601 of 4685 HIV-positive participants (98%) completed the questionnaire [2559 men who have sex with men (MSM), 803 heterosexual men and 1239 women]. Region of recruitment was Europe/Israel, 33%; South America/Mexico, 25%; Africa, 22%; other, 21%. Median age was 36 years [interquartile range (IQR) 29, 44 years]. Forty-five per cent reported white ethnicity and 31% black ethnicity. Two per cent had HIV viral load < 50 HIV-1 RNA copies/mL. Seventeen per cent (767 of 4601) reported CLS-D; 20% of MSM compared with 10% of heterosexual men and 14% of women. MSM were also more likely to report multiple CLS-D partners. Possible risk limitation measures (reported by more than half of those who had CLS-D) were seropositioning (receptive anal CLS-D only) or withdrawal (insertive anal CLS-D always without ejaculation). CLS-D was more commonly reported by participants from South America/Mexico and North America compared with Europe; among heterosexual men and women CLS-D was also more commonly reported among participants from Africa compared with Europe. Knowledge of ART impact on transmission risk was low. CONCLUSIONS: A substantial minority recruited to the START study reported CLS-D at baseline. CLS-D reporting was higher in MSM than heterosexuals and varied significantly according to region of recruitment. A substantial proportion of MSM reporting CLS-D appear to take transmission risk limitation measures.

Decentralised management of drug-resistant tuberculosis (MDR- and XDR-TB) in South Africa: an alternative model of care.

SETTING: A growing number of cases of extensively drug-resistant tuberculosis (XDR-TB) have been reported from KwaZulu-Natal, South Africa. OBJECTIVE: To propose an alternative model to centralised care that can be implemented to alleviate the current emergency. DISCUSSION: The current failing TB programme could be improved by borrowing strategies such as decentralisation of care, treatment expertise, high levels of treatment adherence and successful outcomes, all of which have been successfully implemented in the human immunodeficiency virus programme. Patients with multidrug-resistant or XDR-TB could be admitted to institutions closer to their homes for treatment with subsequent discharge to home-based care. CONCLUSION: The longer we support a failed system or wait for a perfect solution, the more the current devastation will continue to grow.

Characteristics of HIV-1-associated Kaposi's sarcoma among women and men in South Africa.

Despite the increase of HIV-1-associated Kaposi's sarcoma (KS), little is known about HIV-associated KS in the African setting, particularly among women. A descriptive study of the demographic, clinical, immunological and virological features of AIDS-associated KS from KwaZulu-Natal, South Africa was undertaken. Consecutively, recruited patients were clinically staged; CD4/CD8 cell counts, HIV-1 viral loads and clinical parameters were evaluated. Of the 152 patients (77 male and 75 female) 99% were black. Females were significantly younger (P = 0.02) and had poorer disease prognosis (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.4-5.4, P = 0.003) and were more likely to have extensive cutaneous KS when compared with males (OR = 3.1, 95% CI = 1.4-6.7, P = 0.003). One-third of patients had coexisting HIV-related disease, most commonly tuberculosis, and these were more frequent in females (56.7 vs. 43.3%). In conclusion, HIV-associated KS in South Africans has an equal female-to-male ratio. Females are younger and have more severe disease than males.

Training social workers to enhance patient-centered care for drug-resistant TB-HIV in South Africa.

KwaZulu-Natal, South Africa, is the epicenter of an epidemic of drug-resistant tuberculosis (DR-TB) and human immunodeficiency virus (HIV) co-infection, characterized by low rates of medication adherence and retention in care. Social workers may have a unique role to play in improving DR-TB-HIV outcomes. We designed, implemented and evaluated a model-based pilot training course on patient-centered care, treatment literacy in DR-TB and HIV coinfection, patient support group facilitation, and self-care. Ten social workers participated in a 1-day training course. Post-training questionnaire scores showed significant overall gains (P = 0.003). A brief training intervention may be a useful and feasible way to engage social workers in patient-centered care for DR-TB and HIV coinfection.

Le KwaZulu-Natal, en Afrique du Sud, est l'épicentre d'une épidémie de coïnfection par la tuberculose pharmacorésistante (TB-DR) et le virus de l'immunodéficience humaine caractérisée par des taux faibles d'adhérence aux médicaments et de rétention en soins. Les travailleurs sociaux pourraient avoir un rôle unique dans l'amélioration des résultats de la coïnfection TB-DR et VIH. Nous avons conçu, mis en œuvre et évalué une formation pilote basée sur un modèle de soins centré sur le patient, de connaissance du traitement de la coïnfection TB-DR et VIH, de facilitation des groupes de soutien aux patients et de soins auto-administrés. Dix travailleurs sociaux ont participé à une formation d'un jour. Les scores des questionnaires après la formation ont montré des gains d'ensemble significatifs (P = 0,003). Une brève intervention de formation pourrait être une façon utile et faisable d'engager les travailleurs sociaux dans la prise en charge centrée sur le patient coïnfecté par la TB-DR et le VIH.

KwaZulu-Natal, en Suráfrica, es el epicentro de una epidemia de coinfección por el virus de la inmunodeficiencia humana (VIH) y la tuberculosis farmacorresistente (TB-DR), que se caracteriza por bajas tasas de cumplimiento terapéutico y una deficiente retención en la atención. Los trabajadores sociales pueden cumplir una función muy útil en el mejoramiento de los desenlaces clínicos de estos casos. En el presente artículo se describe el diseño, la ejecución y la evaluación de un curso experimental de capacitación a partir de un modelo, sobre la atención centrada en el paciente, la divulgación terapéutica relacionada con la coinfección por el VIH y la TB-DR, la facilitación en grupos de apoyo de pacientes y la autoasistencia. Diez trabajadores sociales participaron en un curso de capacitación de un día de duración. La puntuación de los cuestionarios posteriores a la capacitación reveló progresos notables en general (P = 0,003). Una intervención breve de capacitación puede representar un medio útil y viable para fomentar la participación de los trabajadores sociales en la atención centrada en el paciente de los casos de coinfección por el VIH y la TB-DR.

Re-inventing adherence: toward a patient-centered model of care for drug-resistant tuberculosis and HIV.

BACKGROUND: Despite renewed focus on molecular tuberculosis (TB) diagnostics and new antimycobacterial agents, treatment outcomes for patients co-infected with drug-resistant TB and human immunodeficiency virus (HIV) remain dismal, in part due to lack of focus on medication adherence as part of a patient-centered continuum of care. OBJECTIVE: To review current barriers to drug-resistant TB-HIV treatment and propose an alternative model to conventional approaches to treatment support. DISCUSSION: Current national TB control programs rely heavily on directly observed therapy (DOT) as the centerpiece of treatment delivery and adherence support. Medication adherence and care for drug-resistant TB-HIV could be improved by fully implementing team-based patient-centered care, empowering patients through counseling and support, maintaining a rights-based approach while acknowledging the responsibility of health care systems in providing comprehensive care, and prioritizing critical research gaps. CONCLUSION: It is time to re-invent our understanding of adherence in drug-resistant TB and HIV by focusing attention on the complex clinical, behavioral, social, and structural needs of affected patients and communities.

An outbreak of type 4b Listeria monocytogenes infection involving patients from eight Boston hospitals.

During September and October 1979, 23 patients admitted to hospitals in the Boston area had systemic Listeria monocytogenes infection. Twenty (87%) of these isolates were L monocytogenes type 4b, whereas only nine (33%) of the isolates serotyped during the preceding 26 months had been 4b. Patients with type 4b Listeria infection during the epidemic period (case patients) differed from patients with sporadic Listeria infection in the preceding two years in that more of the case patients had hospital-acquired infection (15/20 vs 4/18), had received antacids or cimetidine before the onset of listeriosis (12/20 vs 3/18), and had gastrointestinal tract symptoms that began at the same time as fever (17/20 vs 4/18). In addition, more case patients took antacids or cimetidine compared with patients matched for age, sex, and date of hospitalization (12/20 vs 10/40). Three foods were preferred by case patients more frequently than by control patients: tuna fish, chicken salad, and cheese. However, the only common feature appeared to be the serving of these foods with raw celery, tomatoes, and lettuce. The raw vegetables may have been contaminated with Listeria, which was able to survive ingestion because of gastric acid neutralization and subsequently to cause enteritis, bacteremia, and meningitis in susceptible hosts. However, we cannot exclude pasteurized milk as a source of this outbreak.

The treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.

Forty-four episodes of Pneumocystis carinii pneumonia (PCP) occurred in 36 of 70 patients with the acquired immunodeficiency syndrome. Thirty-four patients with 40 episodes of PCP were treated with trimethoprim-sulfamethoxazole. Therapy was successful in 18 episodes (45%), but was unsuccessful in 15 episodes (37.5%). In the latter cases, two patients died within 72 hours; 13, of whom nine died, had therapy changed to pentamidine. In seven additional episodes (17.5%), trimethoprim-sulfamethoxazole was changed to pentamidine due to adverse reactions; all patients survived. Seven patients (26% of survivors) developed recurrent PCP. Twenty-two patients (65%) developed adverse reactions to trimethoprim-sulfamethoxazole, including leukopenia (20), hepatotoxicity (12), fever (eight), rash (six), and immediate reactions (two). Reactions were most common during the second week of therapy. Patients with the acquired immunodeficiency syndrome who have PCP have a high trimethoprim-sulfamethoxazole failure rate, due either to adverse reactions or unresponsive infection. Late recurrence is common.

Management strategies for urinary and vaginal infections.

Detailed history, physical examination, laboratory and follow-up data were obtained from 821 women coming to a primary care clinic over a two-year period with the symptoms of urinary tract (UTI) or vaginal infection. Using all available information, each patient retrospectively was given one of several mutually exclusive diagnoses. Vaginitis without UTI was diagnosed in 70% of patients, UTI without vaginitis in 12%, UTI and vaginitis in 2%. The conditional probability of the several possible diagnoses was calculated, given various combinations of clinical data; a diagnosis of vaginitis was twice as likely as a diagnosis of UTI in a patient with dysuria. On the basis of these calculations we identified efficient clinical strategies for when to perform a pelvic examination, a urinalysis, and a urine culture, and when to diagnose UTI presumptively on the basis of urinalysis.

Intravenous drug abusers and the acquired immunodeficiency syndrome (AIDS). Demographic, drug use, and needle-sharing patterns.

We studied the demographic characteristics, drug use patterns, and sexual habits of intravenous (IV) drug abusers to further define this population at risk for acquired immunodeficiency syndrome (AIDS). Sixteen IV drug abuser patients with AIDS, 24 IV drug abuser patients with AIDS-related complex (ARC), and 14 IV drug abuser controls without evidence of AIDS or ARC were evaluated. The subjects in each group were similar demographically, in drug use practice, and in sexual orientation and experience. Of the AIDS and ARC patients, 34 (88%) of 40, including all seven homosexual men, shared needles, as did all drug abusers without AIDS or ARC. Seventy-four percent of patients, including all homosexual men, attended "shooting galleries," where anonymous multiple-partner needle sharing took place. Needle sharing supports the hypothesis of AIDS transmission by a blood-borne route, can explain the spread of AIDS and the high rate of seropositivity to the putative AIDS agent among IV drug abusers, and is a logical link between IV drug abusers and male homosexuals, the two largest groups with AIDS.

Attaining higher goals in HIV treatment: the central importance of adherence.

In recent years, advances in HIV therapeutics have changed the nature of HIV/AIDS disease, so that it has now assumed some of the characteristics of a 'chronic' disease. Several factors have, however, qualified these advances. Social, economic, and clinical variables have confounded universal therapeutic success. Access to the highly active antiretroviral therapy is limited among marginalized populations, such as the homeless, or absent in many nations that have poor resources. In addition, study populations are often not fully representative of those actually cared for in clinical practice, who may respond differently to the study medications. Moreover, physiologic differences between patients may alter drug plasma levels, resulting in varying efficacy levels in different patients. Finally, and crucial among determinants of effective therapy, is a patient's level of adherence to the antiretroviral regimen. The magnitude of 'error-prone' viral replication makes resistance to antiretroviral agents invariable. In the presence of partially suppressive therapy, viral replication will select for viral variants with resistance mutations. Therefore, potent and continuous suppressive therapy for the duration of viral replicative capability is necessary for therapy to be effective. Factors that have an impact on adherence include characteristics of the treatment regimen, of patients and clinicians, and of the clinical setting. Successful adherence to therapeutic regimens is the responsibility of clinicians as well as patients. Many patient- and clinician-focused strategies and interventions that can improve adherence exist. The simplification of current antiviral regimens, without the loss of potency, is essential to achieving the goal of complete adherence. Maximizing the long-term benefit of highly active antiretroviral therapy requires knowledge of the technical and biologic aspects of HIV therapeutics, but necessitates an understanding of the behavioral aspects of therapeutics as well.

End-of-life decisions in HIV-positive patients: the role of spiritual beliefs.

OBJECTIVE: To describe the role of spiritual beliefs in HIV-positive patients' end-of-life decisions. DESIGN: Inperson, cross-sectional survey. SETTING: An HIV/AIDS floor of an urban, university teaching hospital. PATIENTS: Ninety hospitalized HIV-positive patients. MAIN OUTCOME MEASURES: Prior discussions about advance directives, possession of a living will (written advance directive), fear of death, professions of hope and purpose in life, religious beliefs and practices, guilt about HIV infection, and perception of HIV as punishment. RESULTS: Of 104 eligible patients, 90 agreed to be interviewed. Twenty-four per cent of patients had discussed their resuscitation status with a physician and 17% possessed a living will; 44% of patients felt guilty about their HIV infection, 32% expressed fear of death, and 26% felt their disease was some form of punishment. Prior discussions about resuscitation status were less likely in those who perceived HIV as punishment (P=0.009) and more likely in those who believed in God's forgiveness (P=0.043). A living will was more common in those who prayed daily (P=0.025) and in those whose belief in God helped them when thinking about death (P=0.065). Fear of death was more likely in those who perceived HIV as punishment (P=0.01) or felt guilty about having HIV (P=0.039), and less likely in those who read the Bible frequently (P=0.01) or attended church regularly (P=0.015). Outcome measures did not vary significantly according sex, race, HIV risk factors, or education level. CONCLUSIONS: In this HIV-positive population, spiritual beliefs and religious practices appeared to play a role in end-of-life decisions. Discussions about end-of-life decisions may be facilitated by a patient's belief in a forgiving God and impeded by a patient's interpretation of HIV infection as punishment. Health-care providers need to recognize patients' spiritual beliefs and incorporate them into discussions about terminal care.

Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadone.

BACKGROUND: Pharmacokinetic interactions complicate and potentially compromise the use of antiretroviral and other HIV therapeutic agents in patients with HIV disease. This may be particularly so among those receiving treatment for substance abuse. OBJECTIVE: We describe seven cases of opiate withdrawal among patients receiving chronic methadone maintenance therapy following initiation of therapy with the non-nucleoside reverse transcriptase inhibitor, nevirapine. DESIGN: Retrospective chart review. RESULTS: In all seven patients, due to the lack of prior information regarding a significant pharmacokinetic interaction between these agents, the possibility of opiate withdrawal was not anticipated. Three patients, for whom methadone levels were available at the time of development of opiate withdrawal symptoms, had subtherapeutic methadone levels. In each case, a marked escalation in methadone dose was required to counteract the development of withdrawal symptoms and allow continuation of antiretroviral therapy. Three patients continued nevirapine with methadone administered at an increased dose; however, four chose to discontinue nevirapine. CONCLUSION: To maximize HIV therapeutic benefit among opiate users, information is needed about pharmacokinetic interactions between antiretrovirals and therapies for substance abuse.

A prospective comparison of neuropsychologic function in HIV-seropositive and seronegative methadone-maintained patients.

A prospective longitudinal study of neuropsychological and psychosocial functioning in a methadone-maintained population was initiated to test the hypothesis that cognitive impairments may be present early in the course of HIV infection, before the onset of other physical symptoms. A total of 220 methadone-clinic patients without evidence of HIV-related illnesses were given baseline psychological screening tests, as well as serological testing for HIV antibodies. At baseline, 83 (38%) had antibodies to HIV and 137 (62%) did not. On initial testing, controlling for race/ethnicity, age, sex and drug use, the seropositives were more cognitively impaired than the seronegatives. The differences were statistically significant for three subtests on univariate analysis: finger tapping (dominant), digit span (forward) and similarities. Ninety-one patients whose current serological status was known were given follow-up neuropsychological and psychosocial assessments after a mean interval of 7.4 months from baseline testing. At follow-up, seropositives continued to be more cognitively impaired than seronegatives, but there was no deterioration in the performance of the initial seropositives over the time interval.

The spectrum of HIV-1-related disease among outpatients in New York City.

OBJECTIVES: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. DESIGN AND METHODS: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. RESULTS: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. CONCLUSIONS: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.

Increased risk of bacterial pneumonia in HIV-infected intravenous drug users without AIDS.

Although patients with AIDS have been noted to be at risk for bacterial pneumonia as well as opportunistic infections, little is known about the risk of bacterial pneumonia in HIV-infected populations without AIDS. To determine the incidence of bacterial pneumonia in a well defined population of intravenous drug users (IVDUs), and to examine any association with HIV infection, we prospectively studied 433 IVDUs without AIDS, enrolled in a longitudinal study of HIV infection in an out-patient methadone maintenance program. At enrollment, 144 (33.3%) subjects were HIV-seropositive, 289 (66.7%) were seronegative. Over a 12-month period, 14 out of 144 (9.7%) seropositive subjects were hospitalized for community-acquired bacterial pneumonia, compared with six out of 289 (2.1%) seronegative subjects. The cumulative yearly incidence of bacterial pneumonia was 97 out of 1000 for seropositives and 21 out of 1000 for seronegatives (risk ratio = 4.7, P less than 0.001). Eleven out of 14 (78.6%) cases among the seropositive patients were due to either Streptococcus pneumoniae [5] or Hemophilus influenzae [6]. Two out of 14 (14.3%) cases among the seropositives were fatal. Stratifying by level of intravenous drug use indicated that even among subjects not reporting active intravenous drug use at study entry, eight out of 82 (9.8%) seropositives compared with three out of 211 (1.4%) seronegatives were hospitalized for bacterial pneumonia over the study period (risk ratio = 6.9, P less than 0.01). This study shows a markedly increased incidence of bacterial pneumonia associated with HIV infection in IVDUs without AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory markers and the risk of developing HIV-1 disease among injecting drug users.

OBJECTIVE: To characterize the progression to HIV-1 disease among injecting drug users (IDU) according to laboratory markers. DESIGN: Prospective study of cohort of HIV-1-seroprevalent IDU, with case-comparison component. METHODS: Different laboratory markers were examined as predictors of progression to HIV-1-associated diseases including AIDS in a cohort of 318 HIV-1-infected IDU. The cohort was enrolled from a methadone treatment program in the Bronx, New York, USA. The independent utility of non-CD4 cell markers was evaluated after adjustment for the association of low CD4 lymphocyte count with AIDS risk. Clinical events in the natural history of HIV-1 were related to changes in levels of two variables related to duration of infection, CD4 lymphocyte count and serum beta 2-microglobulin (beta 2M) concentration. RESULTS: On univariate analysis, AIDS incidence measured from baseline increased with declining CD4 lymphocyte number and percentage, increasing serum beta 2M level, low platelet count, low leukocyte count and p24 antigenemia. Among HIV-1-related outcomes prior to any AIDS diagnosis, the relative risk of pyogenic bacterial infections conferred by these markers was similar to the relative risk of AIDS. For all HIV-1 outcomes, the elevated risk encountered at CD4 lymphocyte number < or = 200 x 10(6)/l was entirely due to the high risk at < or = 150 x 10(6)/l. On multivariate analysis, control for CD4 lymphocyte count eliminated the association of any other marker with increased AIDS hazard. HIV-1-related outcomes tended to occur in this order: multiple constitutional symptoms, oral candidiasis, pyogenic bacterial infections and AIDS. CONCLUSIONS: In HIV-1-infected IDU, several laboratory markers may predict AIDS when analyzed individually. These are not, however, independently related to increased AIDS risk after adjustment for low CD4 lymphocyte count. A CD4 count < or = 150 x 10(6)/l is more strongly related to immediate risk of adverse outcome than a count of 200 x 10(6)/l. A progressive series of clinical events is associated with markers of duration of HIV-1 infection, prior to and including AIDS diagnosis.