Incident HIV-Associated Wasting/Low Weight Is Associated with Nearly Doubled Mortality Risk in the Modern ART Era.

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016-2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death.

Survival Outcomes in a Pediatric Antiretroviral Treatment Cohort in Southern Malawi.

BACKGROUND: Pediatric uptake and outcomes in antiretroviral treatment (ART) programmes have lagged behind adult programmes. We describe outcomes from a population-based pediatric ART cohort in rural southern Malawi. METHODS: Data were analyzed on children who initiated ART from October/2003 -September/2011. Demographics and diagnoses were described and survival analyses conducted to assess the impact of age, presenting features at enrolment, and drug selection. RESULTS: The cohort consisted of 2203 children <15 years of age. Age at entry was <1 year for 219 (10%), 1-1.9 years for 343 (16%), 2-4.9 years for 584 (27%), and 5-15 years for 1057 (48%) patients. Initial clinical diagnoses of tuberculosis and wasting were documented for 409 (19%) and 523 (24%) patients, respectively. Median follow-up time was 1.5 years (range 0-8 years), with 3900 patient-years of follow-up. Over the period of observation, 134 patients (6%) died, 1324 (60%) remained in the cohort, 345 (16%) transferred out, and 387 (18%) defaulted. Infants <1 year of age accounted for 19% of deaths, with a 2.7-fold adjusted mortality hazard ratio relative to 5-15 year olds; median time to death was also shorter for infants (60 days) than older children (108 days). Survival analysis demonstrated younger age at ART initiation, more advanced HIV stage, and presence of tuberculosis to each be associated with shorter survival time. Among children <5 years, severe wasting (weight-for-height z-score

Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia.

OBJECTIVES: To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. DESIGN: Randomised controlled trial. SETTING: Three public ART facilities in Jimma, Oromia region, Ethiopia. PARTICIPANTS: Adults with HIV eligible for ART with body mass index (BMI) >16. INTERVENTION: Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. OUTCOME MEASURES: Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. RESULTS: Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (-0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/µL (24 to 275 cells/µL), of which 112 cells/µL (15 to 209 cells/µL) were CD8 and 25 cells/µL (-2 to 53 cells/µL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. CONCLUSIONS: Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements containing whey were associated with improved immune recovery. Trial registration Controlled-trials.com ISRCTN32453477.

Maternal mortality among HIV-infected pregnant women in Tanzania.

OBJECTIVE: To investigate risk factors for maternal mortality among HIV-infected women in Tanzania. DESIGN: Prospective cohort study. SETTING: HIV care and treatment clinics in Dar es Salaam, Tanzania. POPULATION: HIV-infected pregnant women. METHODS: Data were collected for all patients enrolled in an HIV/AIDS care and treatment program. Between November 2004 and September 2011, there were 18 917 women pregnant at least once during the follow-up. Thirteen percent of these women had more than one pregnancy, with 21 645 pregnancies occurring. Logistic regression was used to explore the predictors of maternal death among these women. MAIN OUTCOME MEASURES: Maternal mortality. RESULTS: During the study period, 363 maternal deaths occurred, giving a maternal mortality ratio of 1729 [95% confidence interval (CI) 1553-1905] per 100 000 live births. Being wasted [odds ratio (OR) 3.38, 95% CI 2.58-4.45] or anemic (OR 2.26, 95% CI 1.70-3.00) was associated with a higher risk of maternal mortality. Women who were initiated on antiretroviral therapy before their pregnancy had a 55% decreased risk of maternal mortality (95% CI 0.29-0.70) compared with women who were not. The risk of maternal mortality decreased with the length of time on antiretroviral therapy during pregnancy, by 8% for each additional month (OR 0.92, 95% CI 0.88-0.96). CONCLUSIONS: Maternal mortality was high among HIV-infected women. Initiating women on antiretroviral therapy as early as possible and providing nutritional interventions during pregnancy should be considered as means to reduce the maternal mortality among these women.

Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection.

BACKGROUND: Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy. METHODS: We determined the association of MRI-measured regional and total skeletal muscle and adipose tissue with 5-year, all-cause mortality in 922 HIV-infected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). RESULTS: After 5 years of follow-up, HIV-infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23%, compared with 11 and 8% for those in the middle and highest tertiles. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, inflammatory markers, and renal disease, we found that lower arm skeletal muscle, lower leg skeletal muscle and higher visceral adipose tissue (VAT) were each independently associated with increased mortality. Those in the lowest tertile of arm or leg skeletal muscle had higher odds of death [arm: odds ratio (OR) = 2.0, 95% confidence interval (CI) 0.96-4.0; leg: OR = 2.4, 95% CI 1.2-4.8] compared with the highest respective tertiles. Those in the highest tertile of VAT had 2.1-fold higher odds of death (95% CI 1.1-4.0) compared with the lowest VAT tertile. CONCLUSION: Lower muscle mass and central adiposity appear to be important risk factors for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on body mass index in clinical practice.

The benefit of supplementary feeding for wasted Malawian adults initiating ART.

Food insecurity is considered to be an important contributor to HIV associated wasting in sub-Saharan Africa. Low body mass index (BMI) is a strong risk factor for early mortality during antiretroviral therapy (ART). Nutritional supplementation has become standard of care in wasted patients starting ART in many countries in the region, but there is no unequivocal evidence base for this intervention. Against this background, we performed a retrospective study to compare food supplementation versus no nutritional intervention in wasted adults starting ART in Blantyre, Malawi. All patients received free nevirapine, lamivudine, and stavudine. Participants in an effectiveness trial of two food supplements received either corn-soy blend (CSB) or ready-to-use food spread (RUFS) during the first 14 weeks of ART. Results were compared with a historical control group receiving no food supplement that was part of an observational cohort study of outcomes of the same ART regimen. Characteristics on initiation of ART were similar in the three groups, except the use of cotrimoxazole prophylaxis which was more frequent in the food-supplemented groups. Linear regression analysis showed that increase in BMI was greatest in the RUFS group and better in the CSB group than in those receiving no food supplementation at 14 weeks. These differences were no longer significant at 26 weeks. Lower BMI, CD4 count and hemoglobin, WHO clinical stage IV, male gender, and not receiving cotrimoxazole prophylaxis were independent risk factors for mortality at 14 and 26 weeks in the logistic regression analysis. Supplementary food use was not directly associated with improved survival.

Nutritional status of Malawian adults on antiretroviral therapy 1 year after supplementary feeding in the first 3 months of therapy.

OBJECTIVE: To test the hypothesis that individuals on antiretroviral therapy (ART) for 3 months with a greater body mass index (BMI) as a result of supplementary feeding with ready-to-use fortified spread would maintain a higher BMI 9 months after the feeding ended. METHODS: Two cohorts of wasted adults with AIDS, after 12 months of ART and 3 months of supplementary feeding with either ready-to-use fortified spread, an energy dense lipid paste; or corn/soy blended flour, were assessed for clinical and anthropometric status, quality of life, and ART adherence after 3 and 9 months. RESULTS: 336 ART patients participated: 162 who had received ready-to-use fortified spread and 174 who had received corn/soy blended flour. 9 months after stopping food supplements, both groups had a similar BMI, fat-free body mass, hospitalization rate and mortality. Binary logistic regression modelling showed that lower BMI, lower CD4 count, and older age at baseline were associated with a higher risk of death (odds ratio for BMI = 0.63, 95% CI 0.47-0.79). Adherence to the ART regimen and quality of life were similar in both cohorts. CONCLUSION: While supplementary feeding with ready-to-use fortified spread can ameliorate the BMI, an established risk factor for mortality, this effect is sustained only during the time of the intervention. Supplementary feeding of wasted patients for longer than 3 months should be investigated.

Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial.

OBJECTIVE: To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy. DESIGN: Randomised, investigator blinded, controlled trial. SETTING: Large, public clinic associated with a referral hospital in Blantyre, Malawi. PARTICIPANTS: 491 adults with BMI <18.5. INTERVENTIONS: Ready-to-use fortified spread (n=245) or corn-soy blend (n=246). PRIMARY OUTCOMES: changes in BMI and fat-free body mass after 3.5 months. SECONDARY OUTCOMES: survival, CD4 count, HIV viral load, quality of life, and adherence to antiretroviral therapy. RESULTS: The mean BMI at enrolment was 16.5. After 14 weeks, patients receiving fortified spread had a greater increase in BMI and fat-free body mass than those receiving corn-soy blend: 2.2 (SD 1.9) v 1.7 (SD 1.6) (difference 0.5, 95% confidence interval 0.2 to 0.8), and 2.9 (SD 3.2) v 2.2 (SD 3.0) kg (difference 0.7 kg, 0.2 to 1.2 kg), respectively. The mortality rate was 27% for those receiving fortified spread and 26% for those receiving corn-soy blend. No significant differences in the CD4 count, HIV viral load, assessment of quality of life, or adherence to antiretroviral therapy were noted between the two groups. CONCLUSION: Supplementary feeding with fortified spread resulted in a greater increase in BMI and lean body mass than feeding with corn-soy blend. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67515515.

Causes of death in the era of highly active antiretroviral therapy: a retrospective analysis of a hybrid hematology-oncology and HIV practice and the Seattle/King county adult/adolescent spectrum of HIV-related diseases project.

BACKGROUND: HIV-infected patients continue to die in the era of highly active antiretroviral therapy (HAART). OBJECTIVE: To describe the cause of mortality in the HAART era between 2 cohorts by conducting a comparative retrospective analysis. METHODS: The Virginia Mason Medical Center (VMMC) cohort was composed of 60 died HIV-infected patients from 600 patients. The second cohort was comprised of 351 died patients from the Seattle portion of the Adult and Adolescent Spectrum of Diseases Project (Seattle-ASD) of 4721 patients. Among the abstracted data were the conditions present at death, defined as any major cause of morbidity present at death for both cohorts. RESULTS: Non-AIDS defining illnesses (non-ADI) were a major source of mortality in 60% and 45% for the VMMC and Seattle-ASD cohorts, respectively. The most common fatal non-ADI in both cohorts were cancer (7% and 19%), bacterial infections (15%), and liver failure (9% and 14%). Cancer (10%) and wasting (7%) were prominent fatal ADI in both cohorts. In each cohort, patients died despite a nondetectable HIV viral load and a CD4 lymphocyte count >200 cells/microL. This included 11 of 60 (18%) VMMC patients (all of whom died of non-ADI) and 35 of 351 (10%) Seattle-ASD patients (81% died with non-ADI). CONCLUSIONS: In 2 well-characterized urban HIV cohorts, non-ADI were a major cause of mortality in the HAART era. A substantial number of these patients died despite nondetectable HIV viral loads and reasonably well-preserved immune function measured by CD4 cell counts.

Vitamin supplements, socioeconomic status, and morbidity events as predictors of wasting in HIV-infected women from Tanzania.

BACKGROUND: Wasting is a strong independent predictor of mortality in HIV-infected persons. Vitamin supplements delay the disease progression, but their effect on wasting is not known. Data are lacking on the risk factors for wasting in African HIV-infected persons. OBJECTIVES: The objectives were to examine the effect of vitamin supplements on wasting in HIV-infected women and to assess the effects of sociodemographic characteristics, morbidity events, and immunologic progression on the risk of wasting. DESIGN: HIV-infected women (n = 1078) from Tanzania were randomly assigned to receive 1 of 4 daily oral regimens: multivitamins (B complex, C, and E), vitamin A plus beta-carotene, multivitamins that included vitamin A plus beta-carotene, or placebo. The endpoints of the study included first episodes of a midupper arm circumference <22 cm or a body mass index (BMI; in kg/m2) <18 and the incidence of weight loss episodes during a median 5.3 y of follow-up. RESULTS: Multivitamins alone significantly reduced the risk of a first episode of a midupper arm circumference <22 cm (relative risk: 0.66; 95% CI: 0.47, 0.94; P = 0.02). In multivariate-adjusted Cox models, the woman's age, education level, and height were inversely related to the incidence of wasting. Episodes of diarrhea, nausea or vomiting, lower respiratory tract infections, oral ulcers, thrush, severe anemia, and low CD4+ cell counts were each significantly related to an increased risk of wasting. CONCLUSIONS: Vitamins C and E and the vitamin B complex have a protective effect on wasting in HIV-infected women. Prevention of diarrhea, severe respiratory tract infections, and anemia are likely to decrease the burden of wasting.

Effect of recombinant human growth hormone on exercise capacity in patients with HIV-associated wasting on HAART.

Over 700 patients with HIV-associated wasting while receiving HAART were randomly assigned to double-blind treatment for 12 weeks with recombinant human growth hormone (rhGH) daily or on alternate days, or to placebo. Maximum exercise intensity increased by a median of 2.35kJ in the alternate-days group and 2.60 kJ in the daily group but decreased by 0.25kJ in the placebo group. The median difference between the daily and placebo groups was 2.85 kJ (P < .0001). These improvements suggest that rhGH treatment may enable patients with wasting to perform activities of daily living that would be exhausting without rhGH treatment.

Increased body weight and improved quality of life in AIDS patients following V-1 Immunitor administration.

OBJECTIVES: Development of affordable and safe therapy to reverse the loss of body mass is of critical importance since AIDS-related wasting is associated with increased mortality. METHOD: We have demonstrated earlier that oral therapeutic HIV vaccine, V-1 Immunitor (V1), tested in a small group of AIDS patients in Thailand not only increases T-cell counts and decreases the viral load but also results in weight gain and prolonged survival. To further expand this observation, we retrospectively analyzed 650 HIV-positive patients who were followed for an average of 23 weeks. RESULTS: The treatment with V1 resulted in a sustained and statistically significant increase in body mass across the whole population (mean+/-s.e.; 1.5+/-0.4 kg; P=6.5E-015). Among them, 384 (59%) patients gained an average of 4.2+/-0.2 kg; 107 (17%) had unchanged weight; and 159 (24%) had lost 3.8+/-0.3 kg. Thus, the prevailing majority of patients (76%) were able to gain or maintain weight. Treatment was well tolerated; in a survey of health status in a comparable but separate group of 382 patients, about 85% reported subjective improvement after V1 treatment, 6% reported no difference, and 9% of the patients reported minor adverse reactions, which did not last more than 1 week. Subjective improvement coincides with the reduction or clearance of oral thrush or mucocutaneous candidiasis in 87.5% of the patients. CONCLUSIONS: In an open label setting, V1 increases body weight, subjective assessment of quality of life, and is safe and effective for HIV patients with weight loss. These data provide the impetus of using V-1 Immunitor as an affordable and easy-to-administer means of treating AIDS-associated wasting and opportunistic infections.

AIDS wasting syndrome: trends, influence on opportunistic infections, and survival.

The authors examined data from a large cohort of HIV-infected persons to demonstrate recent trends in wasting syndrome, to examine the influence of wasting syndrome on the incidence of other opportunistic illnesses, and to explore if any of the commonly prescribed treatments for wasting are associated with improved survival. Kaplan-Meier analysis and multivariate left-truncated Cox models were used to estimate time to death after the first diagnosis of wasting syndrome and to quantify the association between the covariate and mortality, respectively. The incidence of wasting declined during 1992 through 1999, with the most marked rate of decline occurring after 1995. The incidence of AIDS- and non-AIDS-defining illnesses was generally high at or after a diagnosis of wasting syndrome. Factors significantly associated with improved survival include having a CD4+ count of > or =200 cells/L during the interval of the wasting syndrome diagnosis and antiretroviral therapy with two or more drugs at or after the diagnosis of wasting syndrome. Prescription of oxandrolone was associated with improved survival, but the results did not quite reach statistical significance. The authors' study provides supportive information that treatment of wasting syndrome may have a favorable impact on survival.

Weight loss, wasting, and survival in HIV-positive patients: current strategies.

Wasting syndrome has been a common HIV-related condition reported in the United States. Three analyses from the Tufts Nutrition for Healthy Living study shed new light on the syndrome. Analysis of Cox proportional hazards models showed that losses in weight, fat-free mass, body cell mass, and fat mass, both from baseline weight and from weight at previous follow-up, were all significant indicators of mortality in patients with the HIV wasting syndrome. In the second analysis, the prevalence of 5% weight loss from the previous visit was shown to be 35% greater in the late HAART era, from 1998 to 2003, than in the early HAART era of 1995 to 1997 (P < .02). This corresponds with earlier observations that the diagnosis of HIV wasting had been increasing during the decade of the 1990s. In the third analysis, the researchers found that body weight, fat-free mass, and body mass index improved in patients receiving nutritional intervention compared with patients receiving placebo.

Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks.

BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.

Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy.

Weight loss and wasting have long been established as strong predictors of mortality in HIV-infected patients. Today, despite the effectiveness of highly active antiretroviral therapy (HAART), there is evidence that HIV-related wasting is still an important comorbidity in many patients. We conducted a study to determine if wasting is still associated with decreased survival in patients receiving HAART and which parameter (weight, fat-free mass [FFM], body cell mass [BCM], or fat mass [FM]) is most strongly associated with mortality. The study population consisted of 678 HIV-positive participants enrolled in the Nutrition for Healthy Living study. Weight, FFM, BCM, and FM were assessed for all participants at 6-month intervals. At each follow-up visit, percent losses of each parameter were calculated from values at baseline and the previous visit. Cox proportional hazards models were used to estimate and compare the relative risks of death for each parameter, adjusting for potential confounders such as HAART use, body mass index, and CD4 cell counts. In analyses examining the parameters separately and together in the same model, weight loss emerged as the strongest independent predictor of mortality. Weight loss of >or=10% from baseline or the previous visit was significantly associated with a four- to sixfold increase in mortality compared with maintenance or gaining of weight. Even one episode of weight loss of >or=3% from baseline or >or=5% from the previous visit was predictive of mortality. In summary, despite the apparent benefits of HAART use on HIV-related survival, weight loss remains an independent predictor of mortality. In addition, FFM or BCM estimated using bioelectrical impedance analysis does not add further prognostic value over weight loss.

AIDS in Africa--survival according to AIDS-defining illness.

OBJECTIVE: Evaluation of prognostic significance of the type of AIDS-defining illness (ADI) and performance status in a cohort of AIDS patients. DESIGN, SETTING, SUBJECTS, OUTCOME MEASURES: A retrospective analysis of 280 patients with AIDS, as defined by the proposed World Health Organisation (WHO) clinical staging system, who attended two Cape Town-based HIV clinics between 1984 and 1997. Patients were stratified according to the type of initial ADI. Survival associated with each opportunistic event was determined by Kaplan-Meier analysis. Cox proportional hazard analysis was used to determine relative risk for death associated with three strata of ADI. RESULTS: Median survival associated with various initial ADIs varied from less than 3 months (encephalopathy and wasting), to over 2 years (extrapulmonary tuberculosis and herpes simplex virus infection). This effect of ADI on outcome was most striking in patients with relatively preserved CD4 counts (CD4 > 50/microliter). A performance status score 4 predicted 50% mortality at 1 month, irrespective of co-morbidity. CONCLUSION: The type of ADI is an important determinant of survival, particularly in patients with preserved CD4 counts. The stratification of patients by type of ADI and performance status may be useful in the management of patients with advanced HIV infection in resource-limited environments.

Human immunodeficiency virus-related mortality in infants and children: data from the pediatric pulmonary and cardiovascular complications of vertically transmitted HIV (P(2)C(2)) Study.

OBJECTIVES: To identify the causes of mortality in children with vertically transmitted human immunodeficiency virus (HIV) infection and to study age-related mortality trends. METHODS: In the multicenter P(2)C(2) HIV Study, 816 children born to HIV-infected mothers were followed for a median of 3.6 years. Two hundred five study participants with HIV infection were enrolled at a median age of 23 months; 611 were enrolled either prenatally or in the neonatal period before their HIV infection status was known. There were 121 deaths in study patients. The cause of death for all patients, its relationship to HIV infection, and pulmonary or cardiac involvement were determined. Age trends in disease-specific mortality were summarized for the HIV-related deaths. RESULTS: Ninety-three children died of HIV-related conditions. Infection was the most prevalent cause of death for children under 6 years of age with 32.3% caused by pulmonary infection and another 16.9% caused by nonpulmonary infection. The frequency of pulmonary disease as the underlying cause of death decreased significantly with increasing age: 5/9 (55.6%) by age 1, 1/12 (8.3%) after age 10 years. The frequency of chronic cardiac disease as the underlying cause increased with age-0% by age 1 year, 3/12 (25.0%) after age 10 years, as did the frequency of wasting syndrome with disseminated Mycobacterium avium complex-0% by age 1 year, 6/12 (50.0%) after age 10 years. CONCLUSIONS: Children with HIV who survive longer are less likely to die of pulmonary disease or infection and more likely to die of cardiac causes or with wasting syndrome.pediatric acquired immunodeficiency syndrome, mortality, human immunodeficiency virus.

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

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