Kate Buchacz

Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections.

Background: Syphilitic ulcers are known to facilitate the transmission of HIV infection, but the effect of syphilis infection on HIV viral loads and CD4 cell counts is poorly understood. Methods: We abstracted medical records for HIV-infected male syphilis patients seen at three clinics in San Francisco and Los Angeles from January 2001 to April 2003. We compared plasma HIV-RNA levels and CD4 cell counts during syphilis infection with those before syphilis infection and after syphilis treatment, using the Wilcoxon signed rank test. Results: Fifty-two HIV-infected men with primary or secondary syphilis had HIV viral load and CD4 cell count data available for analysis; 30 (58%) were receiving antiretroviral therapy. Viral loads were higher during syphilis compared with pre-syphilis levels by a mean of 0.22 RNA log10 copies/ml (P = 0.02) and were lower by a mean of −0.10 RNA log10 copies/ml (P = 0.52) after syphilis treatment. CD4 cell counts were lower during syphilis infection than before by a mean of −62 cells/mm3 (P = 0.04), and were higher by a mean of 33 cells/mm3 (P = 0.23) after syphilis treatment. Increases in the HIV viral load and reductions in the CD4 cell count were most substantial in men with secondary syphilis and those not receiving antiretroviral therapy. Conclusion: Syphilis infection was associated with significant increases in the HIV viral load and significant decreases in the CD4 cell count. The findings underscore the importance of preventing and promptly treating syphilis in HIV-infected individuals.

Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda

BACKGROUND Poverty and limited health services in rural Africa present barriers to adherence to antiretroviral therapy that necessitate innovative options other than facility-based methods for delivery and monitoring of such therapy. We assessed adherence to antiretroviral therapy in a cohort of HIV-infected people in a home-based AIDS care programme that provides the therapy and other AIDS care, prevention, and support services in rural Uganda. METHODS HIV-infected individuals with advanced HIV disease or a CD4-cell count of less than 250 cells per muL were eligible for antiretroviral therapy. Adherence interventions included group education, personal adherence plans developed with trained counsellors, a medicine companion, and weekly home delivery of antiretroviral therapy by trained lay field officers. We analysed factors associated with pill count adherence (PCA) of less than 95%, medication possession ratio (MPR) of less than 95%, and HIV viral load of 1000 copies per mL or more at 6 months (second quarter) and 12 months (fourth quarter) of follow-up. FINDINGS 987 adults who had received no previous antiretroviral therapy (median CD4-cell count 124 cells per muL, median viral load 217,000 copies per mL) were enrolled between July, 2003, and May, 2004. PCA of less than 95% was calculated for 0.7-2.6% of participants in any quarter and MPR of less than 95% for 3.3-11.1%. Viral load was below 1000 copies per mL for 894 (98%) of 913 participants in the second quarter and for 860 (96%) of 894 of participants in the fourth quarter. In separate multivariate models, viral load of at least 1000 copies per mL was associated with both PCA below 95% (second quarter odds ratio 10.6 [95% CI 2.45-45.7]; fourth quarter 14.5 [2.51-83.6]) and MPR less than 95% (second quarter 9.44 [3.40-26.2]; fourth quarter 10.5 [4.22-25.9]). INTERPRETATION Good adherence and response to antiretroviral therapy can be achieved in a home-based AIDS care programme in a resource-limited rural African setting. Health-care systems must continue to implement, evaluate, and modify interventions to overcome barriers to comprehensive AIDS care programmes, especially the barriers to adherence with antiretroviral therapy.

AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study.

Objectives:To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era. Design:A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S. HIV clinics. Methods:We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994–2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period. Results:Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/μl) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994–1997, 1998–2002, and 2003–2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003–2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% of opportunistic illness events occurred at CD4 cell counts at least 200 cells/μl. Conclusions:Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003–2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/μl.

Increased Rates of Bone Fracture among HIV-Infected Persons in the HIV Outpatient Study (HOPS) Compared with the US General Population, 2000–2006

BACKGROUND Among persons with HIV infection, low bone mineral density is common and has raised concerns about increased risk of fracture. METHODS We analyzed data from the HIV Outpatient Study (HOPS), an open prospective cohort study of HIV-infected adults who were followed up at 10 US HIV clinics. We assessed rates of first fractures at any anatomic site during the period 2000-2008. We indirectly standardized the rates of fracture in the HOPS to the general population by age and sex, using data from outpatients in the National Hospital Ambulatory Medical Care Survey (NHAMCS-OPD). We examined factors associated with fractures using Cox proportional hazards modeling. RESULTS Among 5826 active HOPS patients whose data were analyzed (median baseline age, 40 years; male sex, 79%; white race, 52%; exposure to antiretroviral therapy, 73%), 233 patients had incident fractures (crude annual rates, 59.6-93.5 fractures per 10,000 persons). Age-standardized fracture rates increased from 2000 to 2002 (P = .01) and stabilized thereafter. Among persons aged 25-54 years, both fracture rates and relative proportion of fragility fractures were higher among HOPS patients than among patients in the NHAMCS-OPD. In addition to older age and substance abuse, nadir CD4+ cell count <200 cells/mm(3) (adjusted hazard ratio [aHR], 1.60; 95% confidence interval [CI], 1.11-2.31), hepatitis C infection (aHR, 1.61; 95% CI, 1.13-2.29) and diabetes (aHR, 1.62; 95% CI, 1.00-2.64) were associated with incident fractures. CONCLUSIONS Age-adjusted fracture rates among HOPS patients were higher than rates in the general US population during the period 2000-2006. Clinicians should regularly assess HIV-infected persons for fracture risk, especially those with low nadir CD4+ cell counts or other established risk factors for fracture.

Low CD4+ T Cell Count Is a Risk Factor for Cardiovascular Disease Events in the HIV Outpatient Study

BACKGROUND Traditional cardiovascular disease (CVD) risk factors, human immunodeficiency virus (HIV) infection, and antiretroviral (ARV) agents have been associated with CVD events in HIV-infected patients. We investigated the association of low CD4(+) T lymphocyte cell count with incident CVD in a cohort of outpatients treated in 10 HIV specialty clinics in the United States. METHODS We studied patients who were under observation from 1 January 2002 (baseline), categorized them according to National Cholesterol Education Program guidelines into 10-year cardiovascular risk score (10-y CVR) groups , and observed them until CVD event, death, last HIV Outpatient Study contact, or 30 September 2009. We calculated rates of incident CVD events and identified associated baseline risk factors using Cox proportional hazard models. We also performed a nested case-control study to examine the association of latest CD4(+) cell count with CVD events. RESULTS Among 2005 patients, 148 experienced incident CVD events. CVD incidence increased steadily from 0.4 to 3.0 events per 100 person-years from lowest to highest 10-y CVR group (P < .001). In multivariable Cox analyses adjusted for 10-y CVR, CD4(+) cell count <350 cells/mm(3) was associated with incident CVD events (hazard ratio, 1.58 [95% confidence interval, 1.09-2.30], compared with >500 cells/mm(3)), suggesting an attributable risk of approximately 20%. In the multivariable case-control analyses, traditional CVD risk factors and latest CD4(+) cell count <500 cells/mm(3), but not cumulative use of ARV class or individual drugs, were associated with higher odds of experiencing CVD events. CONCLUSION CD4(+) count <500 cells/mm(3) is an independent risk factor for incident CVD, comparable in attributable risk to several traditional CVD risk factors in the HIV Outpatient Study cohort.

Amphetamine use is associated with increased HIV incidence among men who have sex with men in San Francisco

We examined the association between amphetamine use and HIV incidence for 2991 men who have sex with men (MSM) who tested anonymously for HIV in San Francisco. HIV incidence among 290 amphetamine users was 6.3% per year (95% CI 1.9–10.6%), compared with 2.1% per year (95% CI 1.3–2.9%) among 2701 non-users (RR 3.0, 95% CI 1.4–6.5). HIV prevention programmes in San Francisco should include efforts to reduce amphetamine use and associated high-risk sexual behaviors.

HIV Infection and Older Americans: The Public Health Perspective

HIV disease is often perceived as a condition affecting young adults. However, approximately 11% of new infections occur in adults aged 50 years or older. Among persons living with HIV disease, it is estimated that more than half will be aged 50 years or older in the near future. In this review, we highlight issues related to HIV prevention and treatment for HIV-uninfected and HIV-infected older Americans, and outline unique considerations and emerging challenges for public health and patient management in these 2 populations.

Rates of hospitalizations and associated diagnoses in a large multisite cohort of HIV patients in the United States, 1994-2005.

ObjectivesTo assess temporal trends in the rates of hospitalizations and associated diagnoses among HIV-infected patients before and during the era of highly active antiretroviral therapy. DesignA prospective cohort study of 7155 patients enrolled in the HIV Outpatient Study at 10 US HIV clinics. MethodsWe evaluated rates of hospitalizations for major categories of medical conditions during 1994–2005 and modeled trends in these rates using multivariable Poisson regression models for repeated observations. We assessed patient characteristics associated with hospitalization using multiple logistic regression. ResultsThe rates of hospitalizations (per 100 person-years) fell from 24.6 in 1994 to 11.8 in 2005 (P < 0.0001). The rates of hospitalizations for AIDS opportunistic infections decreased from 7.6 in 1994–1996 to 1.0 in 2003–2005 (P < 0.0001). AIDS opportunistic infections were present at 31% of hospitalizations in 1994–1996 versus 9.5% in 2003–2005, and chronic end-organ disease conditions were present at 7.2% of such hospitalizations in 1994–1996 versus 14.3% in 2003–2005. Mean CD4+ cell count at hospitalization increased from 115 cells/μl in 1994 to 310 cells/μl in 2005. Factors independently associated with hospitalization in the highly active antiretroviral therapy era (1997–2005) included older age, history of substance abuse, lower CD4+ cell count, history of AIDS, and public health insurance. ConclusionThe rates of hospitalizations for HIV-infected patients declined substantially during 1994–2005, due mainly to reductions in the AIDS opportunistic infections. Compared with the period 1994–1997, patients in the highly active antiretroviral therapy era were hospitalized with higher CD4+ cell counts and more frequently for chronic end-organ conditions.

Predictive accuracy of the veterans aging cohort study index for mortality with HIV infection: A north american cross cohort analysis

Background:By supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1–5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups. Methods:We used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level. Results:Mean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA <500 copies per milliliter (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups. Conclusions:VACS index scores discriminate risk and translate into accurate mortality estimates over 1–5 years of exposure to ART and for diverse patient subgroups from North American.

Antiretroviral therapy improves renal function among HIV-infected Ugandans

Renal dysfunction is a severe complication of advanced HIV disease. We evaluated the impact of highly active antiretroviral therapy (HAART) on renal function among HIV-infected Ugandans in the Home-Based AIDS Care clinical trial. The patients presented with symptomatic HIV disease or CD4 cell count < or = 250 cells/mm(3) and creatinine clearances above 25 ml/min determined by the Cockcroft-Gault equation. Of the 508 patients at baseline, 8% had a serum creatinine over 133 micromol/l and about 20% had reduced renal function evidenced by a creatinine clearance between 25 and 50 ml/min. After 2 years of HAART, the median serum creatinine was significantly decreased by 16% while the median creatinine clearance significantly increased 21%. The median creatinine clearance of patients with renal dysfunction at baseline, increased by 53% during 2 years of treatment. In multivariable analysis, a baseline creatinine above 133 micromol/l, a weight gain of more than 5 kg over the 2 years, female gender and a WHO stage 4 classification were all associated with greater improvements in creatinine clearance on HAART. Our study shows that renal dysfunction was common with advanced HIV disease in Uganda but this improved following 2 years of HAART.