Correlates of Intimate Partner Violence, Including Psychological Partner Violence, in a Multisite U.S. Cohort of People in HIV Care.

We examined past-year intimate partner violence (IPV), including psychological violence without physical/sexual violence, and health outcomes among people with HIV (PWH) in care in a multi-site U.S. cohort. Between 2016 and 2022, PWH reported 12-month psychological, physical, and sexual IPV in a routine assessment. We used linear and logistic regression models adjusted for age, race/ethnicity, and site to examine relationships with health outcomes. Among 9748 PWH (median age 50 years, 81% cisgender male/16% cisgender female/1% transgender female; 44% non-Hispanic white/36% non-Hispanic Black/15% Hispanic), 9.3% (n = 905) reported any IPV in the past 12 months; half reported psychological IPV without physical/sexual IPV (n = 453). PWH reporting any type of IPV were on average younger than those who did not experience IPV. In adjusted models, any IPV was associated with increased likelihood of unstable housing, HIV viral load detection (HIV viral load ≥ 75 copies/mL), moderate-to-severe depressive symptoms, anxiety with panic symptoms, substance use (methamphetamines, cocaine/crack, illicit opioids, marijuana, heavy episodic/hazardous drinking), and concern about exposure to sexually transmitted infection. PWH reporting any IPV in the past 12 months had 4.2% lower adherence to antiretroviral therapy, 2.4 more HIV-related symptoms, a 1.9 point higher HIV stigma score, and a 9.5% lower quality of life score than those without IPV. We found similar associations among PWH reporting only psychological IPV, without physical/sexual IPV. IPV was common among PWH. Half reporting IPV reported only psychological IPV and had similarly poor outcomes as those reporting physical/sexual IPV, demonstrating the need to assess psychological as well as physical and sexual IPV.

RESUMEN: Examinamos la violencia de la pareja íntima (intimate partner violence, IPV) del año anterior, incluida la violencia psicológica sin violencia física y sexual, así como los resultados sanitarios entre las personas con VIH (people with HIV, PWH) que reciben atención en una cohorte multicéntrica de los Estados Unidos. Entre 2016 y 2022, las PWH informaron situaciones de IPV psicológica, física y sexual durante los 12 meses en una evaluación de rutina. Se utilizaron modelos de regresión lineal y logística ajustados por edad, raza/etnia y centro para examinar las relaciones con los resultados sanitarios. Entre 9748 PWH (mediana de edad de 50 años, 81% de hombres cisgénero/16% de mujeres cisgénero/1% de mujeres transgénero; 44% de blancos no hispanos/36% de negros no hispanos/15% de hispanos), el 9,3% (n = 905) informaron haber sufrido algún tipo de IPV en los últimos 12 meses; la mitad informó situaciones de IPV psicológica sin IPV física y sexual (n = 453). Las PWH que informaron de cualquier tipo de IPV fueron, en promedio, más jóvenes que las que no sufrieron IPV. En los modelos ajustados, cualquier IPV se asoció con una mayor probabilidad de vivienda inestable, detección de carga viral del VIH (carga viral del VIH ≥ 75 copias/ml), síntomas depresivos de moderados a graves, ansiedad con síntomas de pánico, consumo de sustancias (metanfetaminas, cocaína/crack, opioides ilícitos, marihuana, consumo excesivo episódico/peligroso de alcohol) y preocupación por la exposición a infecciones de transmisión sexual. Las PWH que informaron alguna situación de IPV en los últimos 12 meses tuvieron un 4,2% menos de cumplimiento de la terapia antirretrovírica, un 2,4% más de síntomas relacionados con el VIH, una puntuación de estigma del VIH 1,9 puntos más alta y una puntuación de calidad de vida un 9,5% más baja que las que no sufrieron IPV. Se encontraron asociaciones similares entre las PWH que informaron solo IPV psicológica, sin IPV física y sexual. La IPV fue común entre las PWH. La mitad de las personas que informaron IPV solo informaron IPV psicológica y tuvieron resultados igualmente deficientes que los que informaron IPV física y sexual, lo que demuestra la necesidad de evaluar la IPV psicológica, al igual que la IPV física y sexual.

Alcohol and drug use severity are independently associated with antiretroviral adherence in the current treatment era.

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.

Anemia risk factors among people living with HIV across the United States in the current treatment era: a clinical cohort study.

BACKGROUND: Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking. METHODS: Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site. RESULTS: This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR. CONCLUSION: Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

Associations of food insecurity and psychosocial measures with diet quality in adults aging with HIV.

People aging with HIV face social stressors which may negatively affect their overall nutrition. Here, we assess relationships between self-reported measures of depression, perceived stress, social support, and food insecurity with diet quality in older adults with HIV. A retrospective analysis of self-reported data from parent study at The University of Alabama at Birmingham 1917 HIV Clinic was performed. The study sample consisted of sixty people living with HIV (PLWH) with controlled HIV infection (<50 copies/mL), aged 50 years or older who participated in a cross-sectional microbiome study. Dietary intake was measured using the NHANES 12-month Food Frequency Questionnaire (FFQ) and three Automated Self-Administered (ASA) 24-hr diet recalls to calculate diet quality scores using the Mediterranean Diet Score (MDS); alternative Healthy Eating Index (aHEI); and the Recommended Food Score (RFS) indices. Food insecurity was measured with the Food Security Questionnaire (FSQ). Participants completed the following psychosocial scales: (1) depression - Patient Health Questionnaire-8 (PHQ8); (2) perceived stress - Perceived Stress Scale (PSS-10); (3) social support - Multidimensional Scale of Perceived Social Support (MSPSS). Linear regression models were used to investigate relationships among variables controlling for gender and income. The cohort was characterized as follows: Mean age 56 ± 4.6 years, 80% African-American, and 32% women. Mean body mass index (BMI) was 28.4 ± 7.2 with 55% reporting food insecurity. Most participants reported having post-secondary education (53%), although 77% reported annual incomes <$20,000. Food insecurity was independently associated with measures of poor dietary intake: aHEI (ß = -0.08, p = .02) and MDS (ß = -0.23, p < 0.01) and with low dietary intake of fibre (ß = -0.27, p = .04), vitamin E (ß = -0.35, p = .01), folate (ß = -0.31, p = .02), magnesium (ß = -0.34, p = .01) and copper (ß = -0.36, p = .01). These data indicate food insecurity is associated with poor diet quality among PLWH. Clinical interventions are needed to improve food access for PLWH of low SES.

Antiretroviral pill count and clinical outcomes in treatment-naïve patients with HIV infection.

OBJECTIVES: Treatment guidelines recommend single-tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple-pill formulations of the same regimen. METHODS: We selected treatment-naïve patients starting one-, two- or three-pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one-pill regimen or a three-pill regimen. RESULTS: Among 11 739 treatment-naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow-up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01-1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84-1.68). We estimate that 77 patients would need to be exposed to a one-pill regimen rather than a three-pill regimen for 1 year to avoid one additional AIDS event or death. CONCLUSIONS: This particular single-tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple-pill formulations.

Application of an embryonated chicken egg model to assess the vector competence of Australian Culicoides midges for bluetongue viruses.

Culicoides biting midges (Diptera: Ceratopogonidae) are vectors of a number of globally important arboviruses that affect livestock, including bluetongue virus (BTV), African horse sickness virus and the recently emerged Schmallenberg virus. In this study, a model using embryonated chicken eggs (ECEs) was utilized to undertake vector competence studies of Australian Culicoides spp. for 13 laboratory-adapted or wild-type virus strains of BTV. A total of 7393 Culicoides brevitarsis were reared from bovine dung, and 3364 Culicoides were induced to feed from ECEs infected with different strains of BTV. Of those, 911 (27%) survived the putative extrinsic incubation period of 9-12 days. In some trials, virus was also transmitted onward to uninfected ECEs, completing the transmission cycle. This model does not rely on the use of colonized midges and has the capacity to assess the vector competence of field-collected insects with strains of virus that have not previously been passaged in laboratory culture systems. There is also potential for this model to be used in investigations of the competence of Culicoides spp. for other arboviruses.

Development and evaluation of real-time PCR assays for bloodmeal identification in Culicoides midges.

Culicoides (Diptera: Ceratopogonidae) midges are the biological vectors of a number of arboviruses of veterinary importance. However, knowledge relating to the basic biology of some species, including their host-feeding preferences, is limited. Identification of host-feeding preferences in haematophagous insects can help to elucidate the transmission dynamics of the arboviruses they may transmit. In this study, a series of semi-quantitative real-time polymerase chain reaction (qPCR) assays to identify the vertebrate host sources of bloodmeals of Culicoides midges was developed. Two pan-reactive species group and seven species-specific qPCR assays were developed and evaluated. The assays are quick to perform and less expensive than nucleic acid sequencing of bloodmeals. Using these assays, it was possible to rapidly test nearly 700 blood-fed midges of various species from several geographic locations in Australia.

Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance.

No consensus has previously been formed regarding the types and presentations of infectious pathogens to be considered as 'opportunistic infections' (OIs) within the setting of biologic therapy. We systematically reviewed published literature reporting OIs in the setting of biologic therapy for inflammatory diseases. The review sought to describe the OI definitions used within these studies and the types of OIs reported. These findings informed a consensus committee (infectious diseases and rheumatology specialists) in deliberations regarding the development of a candidate list of infections that should be considered as OIs in the setting of biologic therapy. We reviewed 368 clinical trials (randomised controlled/long-term extension), 195 observational studies and numerous case reports/series. Only 11 observational studies defined OIs within their methods; no consistent OI definition was identified across studies. Across all study formats, the most numerous OIs reported were granulomatous infections. The consensus group developed a working definition for OIs as 'indicator' infections, defined as specific pathogens or presentations of pathogens that 'indicate' the likelihood of an alteration in host immunity in the setting of biologic therapy. Using this framework, consensus was reached upon a list of OIs and case-definitions for their reporting during clinical trials and other studies. Prior studies of OIs in the setting of biologic therapy have used inconsistent definitions. The consensus committee reached agreement upon an OI definition, developed case definitions for reporting of each pathogen, and recommended these be used in future studies to facilitate comparison of infection risk between biologic therapies.

Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Evaluation of the single-item self-rating adherence scale for use in routine clinical care of people living with HIV.

The self-rating scale item (SRSI) is a single-item self-report adherence measure that uses adjectives in a 5-point Likert scale, from "very poor" to "excellent," to describe medication adherence over the past 4 weeks. This study investigated the SRSI in 2,399 HIV-infected patients in routine care at two outpatient primary HIV clinics. Correlations between the SRSI and four commonly used adherence items ranged from 0.37 to 0.64. Correlations of adherence barriers, such as depression and substance use, were comparable across all adherence items. General estimating equations suggested the SRSI is as good as or better than other adherence items (p's <0.001 vs. <0.001-0.99) at predicting adherence-related clinical outcomes, such as HIV viral load and CD4(+) cell count. These results and the SRSI's low patient burden suggest its routine use could be helpful for assessing adherence in clinical care and should be more widespread, particularly where more complex instruments may be impractical.

The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis.

BACKGROUND: We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). METHODS: The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. RESULTS: Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/µL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. CONCLUSION: While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals.

HIV viral load markers in clinical practice.

Plasma HIV RNA determinations are an important prognostic marker of disease progression and, when used appropriately, provide a valuable tool for the management of individual patients. But what constitutes appropriate use?

Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.

T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels. All four subjects receiving 100 mg twice daily had a decline in plasma HIV RNA to less than 500 copies/ml, by bDNA assay. A sensitive RT-PCR assay (detection threshold 40 copies/ml) demonstrated that, although undetectable levels were not achieved in the 14-day dosing period, there was a 1.96 log10 median decline in plasma HIV RNA in these subjects. This study provides proof-of-concept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of HIV replication comparable to anti-retroviral regimens approved at present.

Racial and ethnic disparities in COVID-19 disease incidence independent of comorbidities, among people with HIV in the US.

OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma HIV RNA.

Quantitative analysis of the relationship between virus expression and disease outcome has been critical for understanding HIV-1 pathogenesis. Yet the amount of viral RNA contained within an HIV-expressing cell and the relationship between the number of virus-producing cells and plasma virus load has not been established or reflected in models of viral dynamics. We report here a novel strategy for the coordinated analysis of virus expression in lymph node specimens. The results obtained for patients with a broad range of plasma viral loads before and after antiretroviral therapy reveal a constant mean viral (v)RNA copy number (3.6 log10 copies) per infected cell, regardless of plasma virus load or treatment status. In addition, there was a significant but nonlinear direct correlation between the frequency of vRNA+ lymph node cells and plasma vRNA. As predicted from this relationship, residual cells expressing this same mean copy number are detectable (frequency <2/10(6) cells) in tissues of treated patients who have plasma vRNA levels below the current detectable threshold (<50 copies/ml). These data suggest that fully replication-active cells are responsible for sustaining viremia after initiation of potent antiretroviral therapy and that plasma virus titers correlate, albeit in a nonlinear fashion, with the number of virus-expressing cells in lymphoid tissue.

Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients.

BACKGROUND: Among HIV-infected patients, hepatitis C virus (HCV) coinfection is associated with lower cholesterol levels, but it remains unclear how it affects cardiovascular outcomes. METHODS: We performed logistic regression to evaluate acute myocardial infarction (AMI) and cerebrovascular disease (CVD) events by HCV status among HIV-infected US veterans in the highly active antiretroviral therapy (HAART) era (1996-2004). We then performed survival analyses to evaluate incident AMI and CVD, exploring antiretroviral therapy (ART) as a time-dependent variable. RESULTS: A total of 19 424 HIV-infected patients [31.6% of whom were HCV-coinfected (HIV/HCV)] contributed 76 376 patient-years of follow-up. HCV coinfection was associated with lower rates of hypercholesterolaemia (18.0% in HIV/HCV vs. 30.7% in HIV-only patients; P<0.001), but higher rates of hypertension (43.8%vs. 35.6%; P<0.0001), type 2 diabetes mellitus (16.2%vs. 11.1%; P<0.0001) and smoking (36.7%vs. 24.7%; P=0.009). Rates of AMI and CVD were significantly higher among HIV/HCV than HIV-only patients: 4.19 vs. 3.36 events/1000 patient-years, respectively (P<0.001), for AMI; and 12.47 vs. 11.12 events/1000 patient-years, respectively (P<0.001), for CVD. When analyses were controlled for diabetes mellitus, hypertension, age and duration of ART, hazard ratios (HRs) among those with HIV/HCV (vs. HIV only) were 1.25 [95% confidence interval (CI) 0.98-1.61; P=0.072] for AMI and 1.20 (CI 1.04-1.38; P=0.013) for CVD. Hypertension (HR 2.05; P<0.001), greater age (HR 1.79; P<0.001) and longer duration (cumulative years) of antiretroviral use (HR 1.12; P=0.0411) were also associated with increased risk of AMI in the adjusted model. CONCLUSIONS: In the HAART era, HCV coinfection was associated with a significantly increased risk of CVD and a trend towards an increased risk of AMI among HIV-infected patients.

Measuring depression levels in HIV-infected patients as part of routine clinical care using the nine-item Patient Health Questionnaire (PHQ-9).

Little is known about the psychometric properties of depression instruments among persons infected with HIV. We analyzed data from a large sample of patients in usual care in two US cities (n=1467) using the nine-item Patient Health Questionnaire (PHQ-9) from the PRIME-MD. The PHQ-9 had curvilinear scaling properties and varying levels of measurement precision along the continuum of depression measured by the instrument. In our cohort, the scale showed a prominent floor effect and a distribution of scores across depression severity levels. Three items had differential item functioning (DIF) with respect to race (African-American vs. white); two had DIF with respect to sex; and one had DIF with respect to age. There was minimal individual-level DIF impact. Twenty percent of the difference in mean depression levels between African-Americans and whites was due to DIF. While standard scores for the PHQ-9 may be appropriate for use with individual HIV-infected patients in cross-sectional settings, these results suggest that investigations of depression across groups and within patients across time may require a more sophisticated analytic framework.

High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.

Quantitative competitive polymerase chain reaction (QC-PCR) methods were used to quantify virion-associated human immunodeficiency virus type-1 (HIV-1) RNA in plasma from 66 patients with Centers for Disease Control stage I to IVC1 infection. HIV-1 RNA, ranging from 100 to nearly 22,000,000 copies per milliliter of plasma (corresponding to 50 to 11,000,000 virions per milliliter), was readily quantified in all subjects, was significantly associated with disease stage and CD4+ T cell counts, and decreased by as much as 235-fold with resolution of primary infection or institution of antiretroviral therapy. Plasma virus levels determined by QC-PCR correlated with, but exceeded by an average of 60,000-fold, virus titers measured by endpoint dilution culture. Quantitation of HIV-1 in plasma by QC-PCR may be useful in assessing the efficacy of antiretroviral agents, especially in early stage disease when conventional viral markers are often negative.

Gastrointestinal complications of HIV infection: changing priorities in the HAART era.

It has now been some 25 years since the initial description of AIDS. Following these observations, the epidemiology, natural history and manifestations of this disease have been well characterised. Intense investigation has better characterised HIV, resulting in the development of effective drug therapies to arrest disease progression. These multidrug combinations, termed highly active antiretroviral therapy or HAART, can suppress the viral load to the undetectable range and secondarily halt the destruction of CD4 T lymphocytes. This virological response is associated with a marked improvement in survival and absence of the many complications related to immunodeficiency. For patients who respond to HAART, the current emphasis is on treating side effects from the medications as well as treating other non-AIDS-related disorders. However, given the cost and complexities of these regimens, there are many patients who continue to present with the classic manifestations of AIDS, and, especially in the developing world, we will continue to see these patients for years to come.