Decrease In CD4 Cell Count Research Articles

Malaria Treatment Efficacy among People Living with HIV: The Role of Host and Parasite Factors

Identification of an effect of HIV-associated immunosuppression on response to antimalarial therapy would help guide management of malaria infection in areas of high HIV prevalence. Therefore, we conducted an observational study of people living with HIV infection in Blantyre, Malawi. Participants who developed malaria were treated with sulfadoxine-pyrimethamine (SP) and followed for 28 days. Molecular markers for SP resistance were measured. One hundred seventy-eight episodes of malaria were assessed. The 28-day cumulative treatment failure rate was 29.1%. In univariate analysis, CD4 cell count was not associated with treatment failure (hazard ratio 0.6, 95% confidence interval 0.3-1.2). Among children, the risk of treatment failure increased with infection with SP-resistant parasites and anemia. Decreased CD4 cell count was not associated with impaired response to antimalarial therapy or diminished ability to clear SP-resistant parasites, suggesting that acquired immunity to malaria is retained in the face of HIV-associated immunosuppression.

The role of human leukocyte antigen E and G in HIV infection

The role of human leukocyte antigen E and G in HIV infection

Lability of Antiretroviral Drug Resistance Mutations - Correlates with Immunological and Virological Responses

This study assessed the relationship between changes in CD4 T-cell count, HIV Viral Load (VL) level and evolutionary patterns in Antiretroviral (ARV) resistance mutations of circulating HIV in those with persistent viraemia despite treatment. The study examined the dynamics of change in resistance mutations to explore potential predictors of evolution in the circulating virus over a prolonged period. Four longitudinal blood samples from 29 HIV-infected Australian patients at RPAH are analysed for the presence of genotypically resistant HIV virus. The subjects had CD4 cells counts (40-670 cells/mm(3)), VL levels (1.7-5.7 log(10) copies/ml), drug resistance mutations, and had been treated with ARV regimens for varying periods between February 1998 and June 2005 (i.e., 88 months). Parametric and nonparametric tests were used to examine changes in CD4 T-cell counts and VL levels, and in frequencies of mutations at different sample points. Nonparametric LOESS fitting curves were used to analyse changes in CD4 T-cell counts and VL levels. During the study period, changes in mean values of CD4 cell counts and VL levels in patients displaying an evolving genotypic resistance profile differed from those without evidence of an evolving mutational pattern; applied for both Reverse-Transcriptase (RT) and Protease (PR) gene profiles. In patients with Evolution-of-Resistance (EoR) at the RT site, there was a significant decrease in mean CD4 cell count during the first 36 months (-194 cells/mm(3), P=0.0466) but no significant change in the last 52 months or thereafter (-10 cells/mm(3), P=0.8464). Conversely, in patients with EoR at the PR site, there was no significant change in mean CD4 cell count during the first 36 months (-30 cells/mm(3), P=0.6187) but a significant decrease (-155 cells/mm(3), P=0.0348) thereafter. In patients without EoR at the RT site, there was no significant change in mean CD4 count during the first 36 months (-12 cells/mm(3), P=0.8371), however, a significant increase in mean CD4 cell count occurred thereafter (+242 cells/mm(3), P=0.0077). Similarly, in patients without EoR at the PR site there was no significant change in mean CD4 count during the first 36 months (-19 cells/mm(3), P=0.6647) and there was a significant increase in the last 52 months (+145 cells/mm(3), P=0.0348). The only significant decrease in mean value of VL levels occurred in patients without EoR associated with NRTIs thereafter (-1.33 log(10) copies/ml, P=0.0477), while no significant changes in mean value of VL levels in patients with/without EoR associated with any ARV drugs at any other time points (-0.65 to +0.15 log(10) copies/ml, P=0.1855 to 0.7958). Low CD4 cell counts (<250 cells/mm(3)) and high VL levels (>4.50 log(10) copies/ml) in the early stage of HIV infection, a significant decrease in CD4 cell counts during the first 36 months (-50 or more cells/mm(3)), and high frequencies of mutations during the first 36 months of antiretroviral regimen (>3 mutations) emerged as potential predictive factors of EoR associated with NRTI/PRI agents thereafter. Stable VL in the first 36 months correlated with lack of lability of resistance mutations thereafter.

Profile of Immunologic Recovery in HIV-Infected Ugandan Adults after Antiretroviral Therapy

HIV infection is characterized by a decrease in total CD4 cell count, rising viral load, as well as an increase in immune activation levels. Increased activation can lead to an increase in apoptosis and contribute to CD4 depletion. We evaluated the clinical and immunologic responses of 23 HIV-positive Ugandan volunteers following initiation of antiretroviral therapy (ART). All volunteers achieved and maintained complete viral suppression within the first 3 months of therapy (p > 0.05). CD4+ and CD8+ T cell activation also decreased significantly, although it never reached the level of HIV negative Ugandan volunteers. Viral suppression and CD4 cell recovery were also associated with an improved profile in CD8+ T cell functional markers, but had no effect on HIV-specific proliferation. We conclude that ART in a cohort of therapy-naive Ugandans with AIDS partially restores but does not fully reverse the immune dysfunction observed in chronic HIV infection.

Highlights of the 20th International Conference on Antiviral Research (ICAR)

The International Conference on Antiviral Research (ICAR) meetings cover all aspects of antiviral research into human viruses. The meeting included two major award lectures, invited plenary speakers and a minisymposium, based this year on HCV. In addition, there were many contributor presentations, both oral and poster. This report focuses on the major highlights of the contributor presentations. A full report, including summaries of all the invited speakers and the pre-conference clinical update satellite symposium, will be included in the International Society of Antiviral Research (ISAR) news to be published in Antiviral Chemistry and Chemotherapy (18.4).

Transmission of multidrug-resistant HIV-1: 5 years of immunological and virological survey

Multidrug resistant HIV-1 acquired at the time of primary infection in two patients persisted for at least 5 years with and without treatment. In each patient, only one back mutation to wild-type codon in the protease gene occurred, and that was concomitantly associated with a marked CD4 cell count decrease. In both cases, infection was caused by CCR5 viruses and no rapid clinical progression to AIDS after primary infection was observed.

Characteristics of ophthalmic symptoms in the 278 patients with human immunodeficiency virus

To investigate the characteristics of ophthalmic symptoms of patients with human immunodeficiency virus (HIV) and to provide reference for early diagnosis and treatment of HIV. The clinical data of 278 patients with HIV, including ophthalmic symptoms and general condition collected from September 2002 to July 2004, were analyzed retrospectively. These patients were from the Central African Republic. Among the 278 patients with HIV, 102 had pathologic changes in the eyes and were accompanied with chronic dissipative symptoms and decreased CD4 cell counts. The pathogen of 278 patients with HIV at the initial reception were airway infection (n = 87, 31.3%), digestive tract infection (n = 65, 23.4%), skin symptoms (n = 55, 19.8%), multiple organ failure (n = 51, 18.4%) and ophthalmic symptoms (n = 20, 7.2%). Ophthalmic symptoms manifested as opportunistic infection and sarcoma formation, such as HIV retinopathy, chronic uveitis, external ophthalmoplegia, ocular herpes, and Kaposi's sarcoma in the eyelid. HIV-related retinopathy was not specific, which manifested as retinal hemorrhage, cotton wool spots, vascular occlusion, retinal necrosis, retinal detachment and ocular nerve atrophy. Many kinds of ophthalmic symptoms might appear in patients with HIV. Severe retinopathy and uveitis are the main causes of ablepsia. Because of neglecting the ophthalmic symptoms in the early stage, many HIV patients suffer from decreased visual acuity, which may severely affect the quality of their lives. Consequently, ophthalmologists should pay more attention to patients in the early stage of HIV.

Interruption of Antiretroviral Treatment in HIV‐Infected Patients with Preserved Immune Function Is Associated with a Low Rate of Clinical Progression: A Prospective Study by AIDS Clinical Trials Group 5170

We sought to determine the safety of treatment interruption (TI) and to identify parameters that would define patients with human immunodeficiency virus (HIV) for whom TI is safer. AIDS Clinical Trials Group 5170 was a multicenter, 96-week-long, prospective study of HIV-infected patients receiving antiretroviral therapy (ART) who had CD4(+) cell counts >350 cells/mm(3) and who underwent TI. A total of 167 patients were enrolled. The median nadir in CD4(+) cell count was 436 cells/mm(3). The initial decrease (i.e., during the first 8 weeks) in CD4(+) cell count after ART interruption was 20 cells/mm(3)/week; the subsequent decrease was 2.0 cells/mm(3)/week until week 96. Both the CD4(+) cell count before enrollment and the increase in CD4(+) cell count during ART predicted early decrease; later decrease was predicted by the level of interleukin-7 at enrollment. A Centers for Disease Control and Prevention (CDC) diagnosis of a category B or C event was made for 2 and 2 patients, respectively (all had CD4(+) cell counts >350 cells/mm(3)). At week 96, 17 patients had CD4(+) cell counts < or =250 cells/mm(3), and 46 patients had resumed ART; 5 patients died (unrelated to HIV or acquired immunodeficiency syndrome). In a multivariate analysis, a higher nadir in CD4(+) cell count (>400 cells/mm(3)), a lower HIV load (<50 copies/mL) at the time of TI, and an HIV load < or =22,000 copies/mL before ART predicted a longer time to the primary end point (CDC category B or C event, death, CD4(+) cell count < or =250 cells/mm(3), or resumption of ART). Disease progression after TI was low in this cohort. A higher nadir in CD4(+) cell count, a lower HIV load before ART, and an HIV load < or =50 copies/mL at the time of TI predicted a longer time to the primary end point.

Fisher/Gullain–Barré overlap syndrome in advanced AIDS

Human immunodeficiency virus-associated Guillain-Barré syndrome typically occurs early in HIV infection before AIDS develops. We report a 56-year-old male AIDS patient, who developed overlapping Fisher/Guillain-Barré syndrome despite markedly decreased CD4 cell counts. Serum anti-GQ1b IgG antibody was positive. His condition improved rapidly after immunoglobulin treatment. This indicates that Fisher/Guillain-Barré syndrome may occur even in severely immunosuppressed patients and that anti-ganglioside antibody production is possibly mediated by a T cell-independent process.

Relapse of HIV-associated nephropathy after discontinuing highly active antiretroviral therapy

F.H., a 53-year-old African American woman presented to her primary care provider with acute renal failure (creatinine 2.7 mg/dl from baseline of 1.3 mg/dl) and proteinuria (1.6 g of protein per 24 h). Her past medical history was significant only for hypertension and asthma. Evaluation revealed a positive HIV antibody and a CD4 cell count of 281 cells/μl. F.H. was started on antiretroviral therapy with zidovudine, and a renal biopsy demonstrated glomerular capillary loop collapse and a tubulointerstitial lymphocyte infiltrate with cystically dilated tubules and atrophy consistent with HIV-associated nephropathy (HIVAN). In addition to her antiretroviral therapy she was treated with an angiotensin-converting enzyme inhibitor and a course of corticosteroids. Her creatinine level peaked at 4.6 mg/dl and proteinuria was at approximately 3 g per 24 h. Over the next 3 years her creatinine and proteinuria levels stabilized as she was treated with zidovudine and lamivudine with a relatively suppressed viral load and rising CD4 cell count (see Fig. 1). In March 1999, she was started on HAART with stavudine, didanosine and efavirenz resulting in complete viral suppression and a rise in the CD4 cell count to approximately 900 copies/μl for 2 years. During this period the creatinine level declined to 1.8 mg/dl and urinary protein dropped to 500 mg per 24 h. In August 2001, F.H. discontinued HAART as a result of the side effects of therapy. Her viral load quickly rose to over 300 000 copies/ml and her renal function worsened, with a creatinine level of 3.8 mg/dl in May 2002. A renal ultrasound revealed small echogenic kidneys, consistent with chronic disease, and renal biopsy confirmed recurrent active HIVAN. F.H. was again treated with corticosteroids and HAART, now consisting of zidovudine/lamivudine/abacavir and efavirenz. Over the next 3 years her viral load was fully suppressed on this regimen and her renal function, although severely compromised, has stabilized (estimated glomerular filtration rate 15 ml/min per 1.73 m2) avoiding the need for renal replacement therapy. In addition, there was a dramatic decline in proteinuria from an estimated 5 g to 1 g per 24 h.Fig. 1: Serum creatinine (mg/dl) and urine protein to creatinine ratio (grams protein/grams creatinine) versus time, during therapy with HAART. The upper bars indicate the antiretroviral treatment regimen during the corresponding time intervals. The fluctuation in HIV viral load in relation to time and treatment is indicated in the upper graph. CD4 cell count (cells/ml) at various points in time is indicated numerically below the treatment bars. The lower graph indicates serum creatinine (▵) and urine protein to creatinine ratios (□) versus time and in relation to the ongoing treatment indicated in the upper treatment bars. ABC, Abacavir; ddI, didanosine; D4T, stavudine; EFV, efavirenz; 3TC, lamivudine; ZDV, zidovudine.Epidemiological studies have shown a correlation between increasing HIV viral load, decreasing CD4 cell count and the occurrence of proteinuria and renal failure [1], as well as a reduction in the incidence of HIVAN in patients treated with HAART [2]. Previous case reports have demonstrated a reversal of acute renal failure and histological changes on biopsy after short courses of antiretroviral therapy [3]. Several observational cohort studies have demonstrated a decreased need for renal replacement therapy for patients treated with antiretroviral therapy compared with those not so treated [4–6]. This case supports the hypothesis that HIVAN can be treated by the suppression of viral replication with HAART, and when initiated early may remove the need for renal replacement therapy and provide long-term stabilization of disease. Unlike the previous reported cases, this case suggests a risk of relapse of disease after discontinuing HAART. This suggests that a history of HIVAN alone may be an indication for indefinite HAART, even with an adequate CD4 cell count and despite mild to moderate side effects.

Temporal Trends in Postseroconversion CD4 Cell Count and HIV Load: The Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985–2002

To determine whether early postseroconversion CD4 cell counts and human immunodeficiency virus (HIV) loads have changed over time. Our analysis was based on 22 cohorts of people with known dates of seroconversion from Europe, Australia, and Canada (Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration). We focused on individuals seroconverting between 1985 and 2002 who had the first CD4 cell count (n=3687) or HIV load (n=1584) measured within 2 years of seroconversion and before antiretroviral use. Linear regression models were used to assess time trends in postseroconversion CD4 cell count and HIV load. Trends in time to key thresholds were also assessed, using survival analysis. The overall median initial CD4 cell count was 570 cells/ microL (interquartile range [IQR], 413-780 cells/ microL). The median initial HIV load was 35,542 copies/mL (IQR, 7600-153,050 copies/mL; on log(10) scale, 3.9-5.2 log(10) copies/mL). The postseroconversion CD4 cell count changed by an average of -6.33 cells/ microL/year (95% confidence interval [CI], -8.47 to -4.20 cells/ microL/year; P<.001), whereas an increase was observed in log(10) HIV load (+0.044 log(10) copies/mL/year; 95% CI, +0.034 to +0.053 log(10) copies/mL/year). These trends remained after adjusting for potential confounders. The probability of progressing to a CD4 cell count of <500 cells/ microL by 24 months from seroconversion increased from 0.66 (95% CI, 0.63-0.69) for individuals who seroconverted before 1991 to 0.80 (95% CI, 0.75-0.84) for those who seroconverted during 1999-2002. These data suggest that, in Europe, there has been a trend of decrease in the early CD4 cell count and of increase in the early HIV load. Additional research will be necessary to determine whether similar trends exist in other geographical areas.

Treatment interruption for convenience, cost cutting and toxicity sparing

Scheduled treatment interruption appears to be an attractive alternative to continuous treatment in reducing side effects and costs and increasing comfort and quality of life by reducing overall drug exposure. The question is whether such an interruption is safe. The development of resistance, treatment failure, and the occurrence of diseases induced by decreasing CD4 cell counts or virological rebound are matters of concern. Fixed-cycle scheduled treatment interruption and CD4 cell-guided treatment interruption have been evaluated in randomized controlled trials. Scheduled treatment interruptions, particularly guided by CD4 cell counts, dramatically reduce drug exposure by approximately 60%. The results regarding toxicity and quality of life are more confusing. Against expectations, most trials show little or no reduction in drug-related toxicity and no increase in quality of life. Antiretroviral treatment interruption strategies reduce costs significantly but have inconclusive effects on toxicity and quality of life. The progression of HIV and development of resistance have been reported; therefore scheduled treatment interruption cannot be recommended over continuous treatment. Interruptions using a lower threshold of at least 350 CD4 cells/microl, lasting less than 3 months, and considering the pharmacological properties of drugs may be safe for most patients.

HIV‐1 Disease Progression in Breast‐Feeding and Formula‐Feeding Mothers: A Prospective 2‐Year Comparison of T Cell Subsets, HIV‐1 RNA Levels, and Mortality

There is conflicting evidence regarding the effects of breast-feeding on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection, and little is known about the effects of breast-feeding on markers of HIV-1 disease progression. HIV-1-seropositive women were enrolled during pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24 postpartum and were compared between breast-feeding and formula-feeding mothers. Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula-feeding women had a higher education level and prevalence of HIV-1-related illness than did breast-feeding women; however, the groups did not differ with respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24 postpartum, CD4 cell counts decreased 3.9 cells/ microL/month (P<.001), HIV-1 RNA levels increased 0.005 log(10) copies/mL/month (P=.03), and body mass index (BMI) decreased 0.03 kg/m(2)/month (P<.001). The rate of CD4 cell count decline was higher in breast-feeding mothers (7.2 cells/ microL/month) than in mothers who never breast-fed (4.0 cells/ microL/month) (P=.01). BMI decreased more rapidly in breast-feeding women (P=.04), whereas HIV-1 RNA levels and mortality did not differ significantly between breast-feeding and formula-feeding women. Breast-feeding was associated with significant decreases in CD4 cell counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a limited adverse impact of breast-feeding in mothers receiving extended care for HIV-1 infection.

Risk factors for high early mortality in patients on antiretroviral treatment in a rural district of Malawi

Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. A cross-sectional analytical study set in Thyolo district, Malawi. Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P </= 0.001) and decreasing CD4 cell counts (chi for trend = 72.4, P </= 0.001). Individuals who were severely malnourished [body mass index (BMI) < 16.0 kg/m] had a six times higher risk of dying in the first 3 months than those with a normal nutritional status. Among individuals starting ART, the BMI and clinical staging could be important screening tools for use to identify and target individuals who, despite ART, are still at a high risk of early death.

Interactions between HIV and malaria in non-pregnant adults: evidence and implications

Interactions between HIV and malaria in non-pregnant adults: evidence and implications

Efectividad inmunológica de las combinaciones de análogos de nucleósidos/nucleótidos, tenofovir + lamivudina, didanosina + lamivudina y tenofovir + didanosina, en pacientes con infección por el VIH y supresión virológica mantenida

Several recent studies have shown that the combination of ddI plus TDF can produce an unexpected drop in CD4 cell counts, even after correcting the ddI dose. Comparative study of the immunological effectiveness of various once-daily NRTI backbones (ddI plus TDF, ddI plus 3TC or TDF plus 3TC) in antiretroviral-experienced HIV-infected patients achieving viral suppression (PCR, HIV-RNA < 50 copies/microl). Prospective cohort study of 48 weeks' duration following viral load suppression with any of the NRTI combinations studied. The main outcome variable was the increase in CD4+ lymphocyte count from the time that viral load was undetectable or treatment was changed for simplification or toxicity (baseline) up to 48 weeks of follow-up. Differences between the assigned therapies were compared. The variables included in analysis were age, sex, risk group, HCV infection, clinical categories of HIV (CDC criteria), lowest CD4 cell count, reason for change of NRTI backbone, type of antiretroviral treatment (PI, NNRTI, or 3 NRTI) and duration of suppressed viral load. RESULTS. Regimens including ddI plus TDF showed significant decreases in CD4 cell counts with adjustments by type of HAART, reason for change, and duration of suppressed viral load. In patients treated with TDF + 3TC, CD4 count increased by 160 cel/microl (95% CI, 53-266) more than in patients treated with TDF + ddI; and in patients receiving ddI + 3TC, CD4+ count increased by 138 cel/microl (95% CI, 25-266) more than in patients receiving TDF + ddI. The ddI plus TDF backbone seems unadvisable because of the lower associated CD4 cell counts, and because it is poorer than the other options from the immunological standpoint.

HIV Type 2 Demyelinating Encephalomyelitis

A human immunodeficiency virus (HIV) type 2 (HIV-2)-infected African patient developed inflammatory demyelinating lesions of the optic nerves, spinal cord, and brain, which coincided with a decreasing CD4 cell count and with active HIV-2 replication. This case provides evidence that HIV-2 is neurotropic, extends the range of known HIV-2-associated neurological complications, and confirms the overlap between the neurological complications of HIV type 1 and HIV-2 infection.

Syphilis and Human Immunodeficiency Virus (HIV)-1 Coinfection: Influence on CD4 T-Cell Count, HIV-1 Viral Load, and Treatment Response

To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. Cases of syphilis diagnosed during 1 year in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25 treated with doxycycline were the same. Syphilis was associated with a decrease in CD4 cell counts and an increase in HIV-RNA levels that both improved after treatment of syphilis.

Association Between Malaria and CD4 Cell Count Decline Among Persons With HIV

To the Editor: Recent information that episodes of Plasmodium falciparum malaria are associated with an average increase of 0.25 log in HIV viral load for approximately 2 months1 supports previous findings of an association between malaria and viral load.2 It is not known whether this level and duration of increase in viral load affect HIV disease progression,3 however, because CD4 cell count measurements, markers of HIV disease progression, were not conducted at follow-up. To examine the potential long-term effects of clinical malaria on HIV disease, we examined data collected during a 2-year cohort study in Uganda.4,5 Participants with HIV infection provided blood for CD4 cell count testing at baseline, at 5 months just before they began cotrimoxazole prophylaxis, and 1.5 years later. Participants were visited at their homes weekly. If they reported fever, we took a blood smear, and if the smear was positive for malaria, we brought treatment to the participant's home within 24 hours. Of 449 HIV-infected persons with available CD4 cell count data for at least 2 time points and no malaria parasitemia at the time of blood draws, baseline CD4 cell counts were <200 cells/μL for 24%, 200 to 500 cells/μL for 45%, and >500 cells/μL for 31%. There were 1024 slides from fever episodes during follow-up, 112 (11%) of which were associated with parasitemia in 92 participants (22.3 episodes of malaria per 100 person-years). The mean time from malaria to the subsequent CD4 cell count was 123 days (range: 7-553 days). Malaria was associated with a more rapid decline in CD4 cell count. Adjusting for sex, age, and baseline CD4 cell count, the mean difference in CD4 cell decline per each additional malaria episode was 40.5 cells/μL per year (95% confidence interval [CI]: 13.1 to 68.0; P = 0.0038). Compared with people with no malaria episodes, the mean difference in annual CD4 cell count decline for persons with 1 episode was 5.4 (95% CI: −63 to 74) cells/μL; for persons with 2 episodes, it was 84 (95% CI: 11 to 157) cells/μL; and for persons with ≥3 episodes, it was 142 (95% CI: −26 to 311) cells/μL. The association between malaria and CD4 cell count decline was seen across all baseline CD4 strata (P = 0.18 for effect modification of baseline CD4 cell count on the relation between malaria and CD4 cell count decline). Although cotrimoxazole prophylaxis was associated with a decreased incidence of malaria, there was no interaction between prophylaxis, malaria, and CD4 cell count decline. A possible reason for the association between malaria and CD4 cell count decline could be that people with more advanced disease at baseline were more likely to have malaria during follow-up, because CD4 cell count has previously been associated with incidence of malaria.6 We controlled for baseline CD4 cell count, however. In our study, people with malaria were treated promptly; yet, there was still an association with CD4 cell count decline. It may be that the immune reaction to malaria persists beyond the period of acute illness and the 8 to 9 weeks of increased HIV viral load. It would be useful for additional studies to examine the effect of malaria on direct outcomes of HIV disease progression, such as morbidity and mortality. The findings that malaria is associated with increased viral load and a more rapid decrease in CD4 cell count support the importance of malaria prevention among persons with HIV, including the routine use of cotrimoxazole prophylaxis and insecticide-treated bed nets. Jonathan Mermin John R. Lule John P. Ekwaru Centers for Disease Control and Prevention-Uganda, Global AIDS Program, Centers for Disease Control and Prevention, Uganda Virus Research Institute, Entebbe, Uganda

Anemia Is an Independent Predictor of Mortality and Immunologic Progression of Disease Among Women With HIV in Tanzania

To examine the association of anemia with mortality and disease progression among a cohort of women with HIV in Dar es Salaam, Tanzania. Time to all-cause death, AIDS-related death, and a 50% decrease in CD4 cell count among 1078 HIV-positive pregnant women enrolled in a clinical trial of vitamin supplementation from 1995-2003. Adjusted models showed that anemia was associated with an increased risk of all-cause mortality (relative hazard [RH]: 2.06, 95% CI: 1.52 to 2.79 for moderate anemia and RH: 3.19, 95% CI: 2.23 to 4.56 for severe anemia) and AIDS-related mortality (RH: 2.21, 95% CI: 1.53 to 3.19 for moderate anemia and RH: 3.47, 95% CI: 2.25 to 5.33 for severe anemia), independent of CD4 cell count, World Health Organization clinical stage, age, pregnancy, vitamin supplementation, and body mass index. Anemia was also associated with a more rapid decline in CD4 counts, measured as time to a 50% drop in CD4 cell count from baseline. Erythrocyte characteristics suggestive of iron deficiency were also associated with all-cause and AIDS-related death and a 50% decline in CD4 cell count. Anemia is an independent predictor of mortality and disease progression in this cohort. Screening for anemia, coupled with prevention and treatment efforts, should be included in HIV care initiatives, particularly those that target women.