Receipt Of Highly Active Antiretroviral Therapy Research Articles

HIV-positive patients in the intensive care unit: A retrospective audit.

The indications for and outcomes of intensive care unit (ICU) admission of HIV-positive patients in resource-poor settings such as sub-Saharan Africa are unknown. To identify indications for ICU admission and determine factors associated with high ICU and hospital mortality in HIV-positive patients. We reviewed case records of HIV-positive patients admitted to the medical and surgical ICUs at Groote Schuur Hospital, Cape Town, South Africa, from 1 January 2012 to 31 December 2012. Seventy-seven HIV-positive patients were admitted to an ICU, of whom two were aged <18 years and were excluded from the final analysis. HIV infection was newly diagnosed in 37.3% of the patients admitted during the study period. HIV-positive patients had a median CD4 count of 232.5 (interquartile range 59 - 459) cells/µL. Respiratory illness, mainly community-acquired pneumonia, accounted for 30.7% of ICU admissions. ICU and hospital mortality rates were 25.3% and 34.7%, respectively. Predictors of ICU mortality included an Acute Physiology and Chronic Health Evaluation ΙΙ (APACHE II) score >13 (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1 - 1.7; p=0.015), receipt of renal replacement therapy (RRT) (OR 2.2, 95% CI 1.2 - 4.1; p=0.018) and receipt of inotropes (OR 2.3, 95% CI 1.6 - 3.4; p<0.001). Predictors of hospital mortality were severe sepsis on admission (OR 2.8, 95% CI 0.9 - 9.1; p=0.07), receipt of RRT (OR 1.9, 95% CI 1.0 - 3.6; p=0.056) and receipt of inotropic support (OR 2.0, 95% CI 1.4 - 3.2; p<0.001). Use of highly active antiretroviral therapy (HAART), CD4 count, detectable HIV viral load and diagnosis at ICU admission did not predict ICU or hospital mortality. Respiratory illnesses remain the main indication for ICU in HIV-positive patients. HIV infection is often diagnosed late, with patients presenting with life-threatening illnesses. Severity of illness as indicated by a high APACHE ΙΙ score, multiple organ dysfunction requiring inotropic support and RRT, rather than receipt of HAART, CD4 count and diagnosis at ICU admission, are predictors of ICU and hospital mortality.

Abstract 3649: Significance of HIV viral load and CD4 count on Kaposi sarcoma in the era of highly active antiretroviral therapy

Abstract Background: Approximately 20% of patients with HIV will have Kaposi Sarcoma (KS) and about half will die within 3 months of diagnosis. Incidence and outcomes of KS have traditionally been linked to CD4 counts <350. More recently, KS has been increasingly described in higher CD4 counts and variable presentations in the era of Highly-Active-Antiretroviral-Therapy (HAART). No studies have established the role of Viral Load (VL) on KS. Objective: To determine the effect of CD4 count and HIV VL on KS presentation and outcomes. Methods: Retrospective review of KS patients with HIV admitted over 12 years (2000-2012). KS patients without HIV infection were excluded. Patients were divided into 4 groups based on CD4 count (≥200 or 100,000 or <100,000). Groups were analyzed with regards to KS severity (good vs poor risk), extent (soft tissue vs visceral), receipt of HAART and survival (6months). Statistical analysis was done via Chi-Square test. Results: 43 patients were included. KS affected predominantly young (30-40yrs), male (93%) HIV patients with VL >100,000 (85%) and CD4 counts 100,000 had a statistically significant increased incidence for visceral involvement (96%, p100,000 ((66.7% with good risk), increased survival (59.4% survived >6months) and less use of HAART (20%). Although, these differences were statistically insignificant. Conclusion: HIV VL of >100,000 is correlated with increased severity and extent of KS. Though statistically insignificant, CD4 counts <200 showed a trend for less severe disease and increased survival despite less use of HAART. Larger prospective studies are warranted to elucidate on these differences. Citation Format: Gentry T. King, Shivani Garg. Significance of HIV viral load and CD4 count on Kaposi sarcoma in the era of highly active antiretroviral therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3649. doi:10.1158/1538-7445.AM2014-3649

Chronic obstructive pulmonary disease: an emerging comorbidity in HIV-infected patients in the HAART era?

The objective of our study was to evaluate the presence of respiratory symptoms and chronic obstructive pulmonary disease (COPD) in a human immunodeficiency virus (HIV)-infected outpatient population and to further investigate the role of highly active antiretroviral therapy (HAART) and other possibly associated risk factors. We consecutively enrolled in a cross-sectional study HIV-infected patients and HIV-negative age, sex and smoking status matched controls. All participants completed a questionnaire for pulmonary symptoms and underwent a complete spirometry. We enrolled 111 HIV-infected patients and 65 HIV-negative age- and sex-matched controls. HIV-infected patients had a significantly higher prevalence of any respiratory symptom (p = 0.002), cough (p = 0.006) and dyspnoea (p = 0.02). HIV-infected patients also had a significantly higher prevalence of COPD in respect of HIV-negative controls (p = 0.008). Furthermore, HIV-infected individuals had significantly (p = 0.002) lower forced expiratory volume at one second (FEV1) and FEV1/forced vital capacity (FVC) ratio (Tiffeneau index) (p = 0.028), whereas the total lung capacity (TLC) was significantly higher (p = 0.018). In the multivariate analysis, significant predictors of respiratory symptoms were current smoking [adjusted odds ratio (AOR) 11.18; 95 % confidence interval (CI) 3.89-32.12] and previous bacterial pneumonia (AOR 4.41; 95 % CI 1.13-17.13), whereas the only significant predictor of COPD was current smoking (AOR 5.94; 95 % CI 1.77-19.96). HAART receipt was not associated with respiratory symptoms nor with COPD. We evidenced a high prevalence of respiratory symptoms and COPD among HIV-infected patients. HIV infection, current cigarette smoking and previous bacterial pneumonia seem to play a significant role in the development of respiratory symptoms and COPD. Thus, our results suggest that the most at-risk HIV-infected patients should be screened for COPD to early identify those who may need specific treatment.

Metabolic syndrome among HIV-infected Taiwanese patients in the era of highly active antiretroviral therapy: prevalence and associated factors

Metabolic complications related to antiretroviral therapy are rarely investigated among HIV-infected patients in Asian countries. We investigated the prevalence of and factors associated with metabolic syndrome among HIV-infected patients who are ethnic Chinese in the era of highly active antiretroviral therapy (HAART). A cross-sectional survey was performed to collect information on the demographic and clinical characteristics and antiretroviral therapy prescribed in 877 HIV-infected patients at a university hospital in Taiwan from May 2008 to April 2009. The modified Adult Treatment Panel III criteria were used to define metabolic syndrome after adjusting for the waist circumference criteria for Asians. Of the 877 patients, 75.3% were male homosexuals, 80.7% were receiving HAART and 88.7% had CD4 counts ≥ 200 cells/mm(3). Metabolic syndrome was diagnosed in 210 patients (26.2%). After adjusting for age, gender, smoking status, family history of diabetes mellitus, cardiovascular disease and hypertension, and baseline CD4 and plasma HIV RNA load, use of protease inhibitors (PIs) was significantly associated with the presence of metabolic syndrome (OR 1.63; 95% CI 1.10-2.43). In addition, exposure to PI for ≥ 3 years, to HAART for ≥ 6 years and to nucleoside reverse transcriptase inhibitor(s) for ≥ 6 years was significantly associated with the presence of metabolic syndrome with an adjusted OR of 1.96 (95% CI 1.13-3.42), 1.78 (95% CI 1.03-3.07), and 1.91 (95% CI 1.11-3.30), respectively. Approximately one-fourth of HIV-infected Taiwanese patients developed metabolic syndrome in the HAART era. Receipt of HAART and prolonged exposure to PI and nucleoside reverse transcriptase inhibitor(s) were associated with metabolic syndrome.

Survival of HIV-infected patients admitted to the intensive care unit in the era of highly active antiretroviral therapy

We retrospectively studied outcomes for HIV-infected patients admitted to the intensive care unit (ICU) between January 1999 and June 2009. Patient demographics, receipt of highly active antiretroviral therapy (HAART), reason for ICU admission and survival to ICU and hospital discharge were recorded. Comparison was made against outcomes for general medical patients contemporaneously admitted to the same ICU. One hundred and ninety-two HIV-infected patients had 222 ICU admissions; 116 patients required mechanical ventilation (MV) and 43 required renal replacement therapy. ICU admission was due to an HIV-associated diagnosis in 113 patients; 37 had Pneumocystis pneumonia. Survival to ICU discharge and hospital discharge for HIV-infected patients was 78% and 70%, respectively, and was 75% and 68% among 2065 general medical patients with 2274 ICU admissions; P = 0.452 and P = 0.458, respectively. HIV infection was newly diagnosed in 42 patients; their ICU and hospital survival was 69% and 57%, respectively. From multivariable analysis, factors associated with ICU survival were patient's age (odds ratio [OR] = 0.74 [95% confidence interval (CI) = 0.53-1.02] per 10-year increase), albumin (OR = 1.05 [1.00-1.09] per 1 g/dL increase), Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR = 0.55 [0.35-0.87] per 10 unit increase), receipt of HAART (OR = 2.44 [1.01-4.94]) and need for MV (OR = 0.14 [0.06-0.36]). In the era of HAART, HIV-infected patients should be offered ICU admission if it is likely to be of benefit.

12 Intensive care

From the start of the HIV epidemic, respiratory failure has been the most common indication for patients with HIV infection to be admitted to the intensive care unit (ICU). In the era of highly active antiretroviral therapy (HAART), Pneumocystis jirovecii pneumonia (PCP), bacterial pneumonia and tuberculosis continue to be significant causes of respiratory failure; however, admission to the ICU with non-HIV-associated respiratory causes, including emphysema and asthma, is increasingly encountered [1–3]. An emerging cause of respiratory failure requiring admission to the ICU is immune reconstitution inflammatory syndrome (IRIS) [4]. Non-respiratory causes, including renal and hepatic failure, cardiac disease, drug overdose and severe toxicity from HIV therapy are increasingly recognised [1–4]. Early in the HIV epidemic, HIV-seropositive patients with critical illnesses were deemed incurable. ICU mortality rates were high and long-term survival rates were low [5–7]. The majority of admissions to the ICU were patients with severe PCP. As a direct result of HAART, there has been a sustained reduction in HIV-associated morbidity and mortality. Several studies report improved outcomes for HIV-seropositive patients requiring admission to the ICU in the HAART era [1–3,8,9]. One recent study suggests that outcomes from ICU admission for HIV-seropositive patients are equivalent to those for the general medical (non-HIV-infected) population [3]. HIV-seropositive patients should not be refused ICU admission based merely on the patient's HIV-serostatus (category IV recommendation). Improved survival from HIV-associated PCP after 1996 has been shown to be independent of the use of HAART and likely reflect general improvements in the ICU management of acute lung injury (ALI) [10]. All HIV-seropositive patients with ALI/acute respiratory distress syndrome (ARDS) who are mechanically ventilated should be managed using the same protocols for management of ALI/ARDS as among general populations – with low tidal volumes and controlled plateau pressures, for example using the ARDS Network guidelines [11] (category IV recommendation). It is currently unclear whether starting HAART on the ICU confers improved outcome for HIV-seropositive patients admitted to the ICU [1,3,10]. In such patients, the short-term effect of HIV RNA level and CD4 cell count on mortality is unclear. Among HIV-seropositive patients already in receipt of HAART, there was no apparent improvement in survival when compared with HIV-seropositive patients not taking HAART [3]. The use of HAART in severely unwell HIV-seropositive patients is confounded by several issues, including drug absorption, requirements for dose modification in the presence of intercurrent renal- and hepatic-induced disease, drug–drug interactions (see Table 12.1), HAART-associated toxicity and IRIS. In some circumstances it may be more appropriate to change HIV therapy rather than dose modify. Advice should be sought from an HIV clinician and/or pharmacist prior to planned modification of HAART. Expert daily consultation between HIV and ICU physicians is essential in the management of critically-ill HIV-seropositive patients admitted to the ICU. Additionally, the advice of a pharmacist with expertise of treatment of HIV-associated infection should be sought. In some cases this expertise will be obtained by transfer of the patient to a tertiary centre (category IV recommendation).

The effect of highly active antiretroviral therapy on the survival of HIV-infected children in a resource-deprived setting: a cohort study.

The effect of highly active antiretroviral therapy (HAART) on the survival of HIV-infected children has not been well quantified. Because most pediatric HIV occurs in low- and middle-income countries, our objective was to provide a first estimate of this effect among children living in a resource-deprived setting. Observational data from HAART-naïve children enrolled into an HIV care and treatment program in Kinshasa, Democratic Republic of the Congo, between December 2004 and May 2010 were analyzed. We used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure. At the start of follow-up, the median age of the 790 children was 5.9 y, 528 (66.8%) had advanced or severe immunodeficiency, and 405 (51.3%) were in HIV clinical stage 3 or 4. The children were observed for a median of 31.2 mo and contributed a total of 2,089.8 person-years. Eighty children (10.1%) died, 619 (78.4%) initiated HAART, six (0.8%) transferred to a different care provider, and 76 (9.6%) were lost to follow-up. The mortality rate was 3.2 deaths per 100 person-years (95% confidence interval [CI] 2.4-4.2) during receipt of HAART and 6.0 deaths per 100 person-years (95% CI 4.1-8.6) during receipt of primary HIV care only. The mortality hazard ratio comparing HAART with no HAART from a marginal structural model was 0.25 (95% CI 0.06-0.95). HAART reduced the hazard of mortality in HIV-infected children in Kinshasa by 75%, an estimate that is similar in magnitude but with lower precision than the reported effect of HAART on survival among children in the United States. Please see later in the article for the Editors' Summary.

Prevalence, severity, and duration of thrombocytopenia among HIV patients in the era of highly active antiretroviral therapy

Thrombocytopenia is a clinically relevant outcome in HIV. However, the epidemiology of this condition, including frequency, severity, and duration, has not been well-characterized in the era of highly active antiretroviral therapy (HAART). In this study, we describe the epidemiology of thrombocytopenia using two methods. We conducted a systematic review of the literature published between 1997 and 2009 to characterize the frequency of thrombocytopenia in different populations in the HAART era. Secondly, we examined the frequency, severity, and duration of thrombocytopenia among HIV patients in the Collaborations in HIV Outcomes Research/US (CHORUS) Cohort from 1997 to 2006 and among HIV patients participating in GlaxoSmithKline HIV Clinical Trials between 1996 and 2004. Prevalence estimates of thrombocytopenia (<150 000 platelets/µl) in the literature varied greatly but were generally above 10%. The thrombocytopenia prevalence estimates in the CHORUS Cohort and the HIV Clinical Trials were both 14%. In the CHORUS Cohort, the platelet count was ≤50 000/µl among 3.1% and ≤30 000/µl among 1.7%; in the HIV clinical trials database, the platelet count was ≤50 000/µl among 1.3% and ≤30 000/µl among 0.67%. Duration of severe thrombocytopenia varied greatly, with the medium duration to ≥75 000 platelets/µl taking 147 days in the CHORUS Cohort and 33 days in the HIV clinical trials database. Among 111 patients with severe thrombocytopenia in the CHORUS Cohort, 23% never achieved a higher platelet count over follow-up. In conclusion, while the prevalence of severe thrombocytopenia was low, it occurred at levels associated with bleeding and was persistent among a small proportion of patients despite receipt of HAART.

Drug Use and Receipt of Highly Active Antiretroviral Therapy among HIV-Infected Persons in Two U.S. Clinic Cohorts

ObjectiveDrug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN) and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD) between 1999 and 2005.MethodsParticipants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care.Results1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45–0.84] and OR = 0.58, 95% CI: [0.46–0.73], respectively for CCC and JHU) and less time on HAART at JHU (0.70, [0.55–0.88]), but not statistically associated with time on HAART at CCC (0.78, [0.56–1.09]). NIDU was independently associated with decreased HAART receipt (0.62, [0.47–0.81]) and less time on HAART (0.66, [0.52–0.85]) at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period.ConclusionsPersons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization.

HIV-related medical service use by rural/urban residents: a multistate perspective

Objective: Geographic location may be related to the receipt of quality HIV health care services. Clinical outcomes and health care utilization were evaluated in rural, urban, and peri-urban patients seen at high-volume US urban-based HIV care sites. Methods: Zip codes for 8773 HIV patients followed in 2005 at seven HIV Research Network sites were categorized as rural (population <10,000), peri-urban (10,000–100,000), and urban (>100,000). Clinical and demographic characteristics, inpatient and outpatient (OP) utilization, AIDS-defining illness rates, receipt of highly active antiretroviral therapy (HAART), opportunistic infection (OI) prophylaxis usage, and virologic suppression were compared among patients, using χ2 tests for categorical variables, t-tests for means, and logistic regression for HAART utilization. Results: HIV-infected rural (n=170) and peri-urban (n=215) patients were less likely to be Black or Hispanic than urban HIV patients. Peri-urban subjects were more likely to report MSM as their HIV risk factor than rural or urban subjects. Age, gender, CD4 or HIV-RNA distribution, virologic suppression, HAART usage, or OI prophylaxis did not differ by geographic location. In multivariate analysis, rural and peri-urban patients were less likely to have four or more annual outpatient visits than urban patients. Rural patients were less likely to receive HAART if they were Black. Overall, geographic location (as defined by home zip code) did not affect receipt of HAART or OI prophylaxis. Conclusion: Although demographic and health care utilization differences were seen among rural, peri-urban, and urban HIV patients, most HIV outcomes and medication use were comparable across geographic areas. As with HIV care for urban-dwelling patients, areas for improvement for non-urban HIV patients include access to HAART among minorities and injection drug users.

Admissions to intensive care unit of HIV-infected patients in the era of highly active antiretroviral therapy: etiology and prognostic factors

IntroductionAlthough access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era.MethodsMedical records of all HIV-infected adults who were admitted to ICU at a university hospital in Taiwan from 2001 to 2010 were reviewed to record information on patient demographics, receipt of HAART, and reason for ICU admission. Factors associated with hospital mortality were analyzed.ResultsDuring the 10-year study period, there were 145 ICU admissions for 135 patients, with respiratory failure being the most common cause (44.4%), followed by sepsis (33.3%) and neurological disease (11.9%). Receipt of HAART was not associated with survival. However, CD4 count was independently predictive of hospital mortality (adjusted odds ratio [AOR], per-10 cells/mm3 decrease, 1.036; 95% confidence interval [CI], 1.003 to 1.069). Admission diagnosis of sepsis was independently associated with hospital mortality (AOR, 2.91; 95% CI, 1.11 to 7.62). A hospital-to-ICU interval of more than 24 hours and serum albumin level (per 1-g/dl decrease) were associated with increased hospital mortality, but did not reach statistical significance in multivariable analysis.ConclusionsRespiratory failure was the leading cause of ICU admissions among HIV-infected patients in Taiwan. Outcome during the ICU stay was associated with CD4 count and the diagnosis of sepsis, but was not associated with HAART in this study.

S82 Survival of HIV-infected patients admitted to the intensive care unit

BackgroundSeveral studies from USA and Europe have suggested the outcome for HIV-infected patients admitted to the intensive care unit (ICU) has improved, concurrent with both the introduction of highly active...

Contraceptive Use and Method Preference among Women in Soweto, South Africa: The Influence of Expanding Access to HIV Care and Treatment Services

ObjectivePreventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa.MethodsWe used survey data from 563 sexually active, non-pregnant women (18–44 years) recruited from the Perinatal HIV Research Unit in Soweto (May–December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use.ResultsOverall, 78% of women reported using contraception, with significant variation by HIV status: 86% of HAART users, 82% of HAART-naïve women, and 69% of HIV-negative women (p<0.0001). In adjusted models, compared with HIV-negative women, women receiving HAART were significantly more likely to use contraception while HAART-naïve women were non-significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI: 0.88, 2.85; respectively). Among HIV-positive women, HAART users were non-significantly more likely to use contraception compared with HAART-naïve women (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of barrier (primarily male condoms), permanent, and dual protection contraceptive methods.ConclusionAmong HIV-positive women receiving HAART, the observed higher prevalence of contraceptive use overall and condoms in particular promises to yield fewer unintended pregnancies and reduced risks of vertical and sexual HIV transmission. These findings highlight the potential of integrated HIV and reproductive health services to positively impact maternal, partner, and child health.

Effectiveness of Varicella Vaccine in Children Infected with HIV

Although varicella vaccine is given to clinically stable human immunodeficiency virus (HIV)-infected children, its effectiveness is unknown. We assessed its effectiveness by reviewing the medical records of closely monitored HIV-infected children, including those receiving highly active antiretroviral therapy (HAART) between 1989 and 2007. Varicella immunization and development of varicella or herpes zoster were noted. Effectiveness was calculated by subtracting from 1 the rate ratios for the incidence rates of varicella or herpes zoster in vaccinated versus unvaccinated children. The effectiveness of the vaccine was 82% (95% confidence interval [CI], 24%-99%; P = .01) against varicella and was 100% (95% CI, 67%-100%; P < .001) against herpes zoster. When the analysis was controlled for receipt of HAART, vaccination remained highly protective against herpes zoster.

HAART receipt and viral suppression among HIV-infected patients with co-occurring mental illness and illicit drug use

Mental illness (MI) and illicit drug use (DU) frequently co-occur. We sought to determine the individual and combined effects of MI and DU on highly active antiretroviral therapy (HAART) receipt and HIV-RNA suppression among individuals engaged in HIV care. Using 2004 data from the HIV Research Network (HIVRN), we performed a cross-sectional study of HIV-infected patients followed at seven primary care sites. Outcomes of interest were HAART receipt and virological suppression, defined as an HIV-RNA <400 copies/ml. Independent variables of interest were: (1) MI/DU; (2) DU only; (3) MI only; and (4) Neither. We used chi-squared analysis for comparison of categorical variables, and logistic regression to adjust for age, race, sex, frequency of outpatient visits, years in clinical care, CD4 nadir, and study site. During 2004, 10,284 individuals in the HIVRN were either on HAART or HAART eligible defined as a CD4 cell count ≤350. Nearly half had neither MI nor DU (41%), 22% MI only, 15% DU only, and 22% both MI and DU. In multivariate analysis, co-occurring MI/DU was associated with the lowest odds of HAART receipt (Adjusted Odds Ratio: 0.63 (95% CI: (0.55–0.72]), followed by those with DU only (0.75(0.63–0.87)), compared to those with neither. Among those on HAART, concurrent MI/DU (0.66 (0.58–0.75)), DU only (0.77 (0.67–0.88)), were also associated with a decreased odds of HIV-RNA suppression compared to those with neither. MI only was not associated with a statistically significant decrease in HAART receipt (0.93(0.81–1.07)) or viral suppression (0.93 (0.82–1.05)) compared to those with neither. Post-estimation testing revealed a significant difference between those with MI/DU and DU only, and MI/DU and MI only. Co-occurring MI and DU is associated with lower HAART receipt and viral suppression compared to individuals with either MI or DU or neither. Integrating HIV, substance abuse, and mental healthcare may improve outcomes in this population.

Rate of Comorbidities Not Related to HIV Infection or AIDS among HIV‐Infected Patients, by CD4 Cell Count and HAART Use Status

The rate of comorbidities not related to human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) among HIV-infected patients may be higher than expected. We assessed the incidence of comorbidities not related to HIV infection or AIDS by CD4 cell count and highly active antiretroviral therapy (HAART) use status in an HIV clinical practice. A total of 2824 patients contributed 9172 person-years of longitudinal data during the period 1997-2006. Among patients with a CD4 cell count <350 cells/mm(3), receipt of HAART was associated with a significantly decreased incidence of comorbidities not related to HIV infection or AIDS.

Outcomes of Cryptococcal Meningitis in Uganda Before and After the Availability of Highly Active Antiretroviral Therapy

Cryptococcal meningitis (CM) is the proximate cause of death in 20%-30% of persons with acquired immunodeficiency syndrome in Africa. Two prospective, observational cohorts enrolled human immunodeficiency virus (HIV)-infected, antiretroviral-naive persons with CM in Kampala, Uganda. The first cohort was enrolled in 2001-2002 (n = 92), prior to the availability of highly active antiretroviral therapy (HAART), and the second was enrolled in 2006-2007 (n = 44), when HAART was available. Ugandans presented with prolonged CM symptoms (median duration, 14 days; interquartile range, 7-21 days). The 14-day survival rates were 49% in 2001-2002 and 80% in 2006 (P < .001). HAART was started 35 +/- 13 days after CM diagnosis and does not explain the improved 14-day survival rate in 2006. In 2006-2007, the survival rate continued to decrease after hospitalization, with only 55% surviving to initiate HAART as an outpatient. Probable cryptococcal-related immune reconstitution inflammatory syndrome occurred in 42% of patients, with 4 deaths. At 6 months after CM diagnosis, 18 persons (41%) were alive and receiving HAART in 2007. The median cerebral spinal fluid (CSF) opening pressure was 330 mm H(2)O; 81% of patients had elevated pressure (>200 mm H(2)O). Only 5 patients consented to therapeutic lumbar puncture. There was a trend for higher mortality for pressures >250 mm H(2)O (odds ratio [OR], 2.1; 95% confidence interval [CI], 0.9-5.2; P = .09). Initial CSF WBC counts of <5 cells/mL were associated with failure of CSF sterilization (OR, 17.3; 95% CI, 3.1-94.3; P < .001), and protein levels <35 mg/dL were associated with higher mortality (OR, 2.0; 95% CI, 1.2-3.3; P = .007). Significant CM-associated mortality persists, despite the administration of amphotericin B and HIV therapy, because of the high mortality rate before receipt of HAART and because of immune reconstitution inflammatory syndrome-related complications after HAART initiation. Approaches to increase acceptance of therapeutic lumbar punctures are needed.

Access to HAART and utilization of inpatient medical hospital services among HIV-infected patients with co-occurring serious mental illness and injection drug use

Objective Among HIV-infected individuals, we examined whether having co-occurring serious mental illness (SMI) and injection drug use (IDU) impacts: (a) receipt of highly active antiretroviral therapy (HAART), and (b) utilization of inpatient HIV services, compared to those who have SMI only, IDU only or neither SMI nor IDU. Method Demographic, clinical and resource utilization data were collected from medical records of 5119 patients in HIV primary care at four US HIV care sites in different geographic regions with on-site mental health services in 2001. We analyzed receipt of HAART using multivariate logistic regression and the number of medical hospital admissions using multivariate logistic and Poisson regression analyses, which controlled for demographic factors, receipt of HAART, CD4 count and HIV-1 RNA. Results Those with co-occurring SMI and IDU [adjusted odds ratio (AOR)=0.52; 95% confidence interval (95% CI)=0.41–0.81] and those with IDU alone (AOR=0.64; 95% CI=0.58–0.85) were significantly less likely to receive HAART than those with neither SMI nor IDU, controlling for demographic and clinical factors. Those with co-occurring SMI and IDU were more likely to use any inpatient medical services (AOR=2.22; 95% CI=1.64–3.01) and were significantly more likely to use them more frequently (incidence rate ratio=1.33; 95% CI=1.13–1.55) than those with neither SMI nor IDU, SMI only or IDU only. Conclusion HIV-infected individuals with co-occurring SMI and IDU are significantly more likely to utilize HIV-related medical inpatient services than individuals with no comorbidity or with only one comorbidity. Individuals with both SMI and IDU did not differ from those with IDU only in receipt of HAART. Inpatient hospitalizations are expensive, and efforts should be targeted towards these populations to reduce potentially avoidable inpatient care.

Pregnancy and HIV Disease Progression during the Era of Highly Active Antiretroviral Therapy

Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.

A High Incidence of Lactic Acidosis and Symptomatic Hyperlactatemia in Women Receiving Highly Active Antiretroviral Therapy in Soweto, South Africa

Lactic acidosis and symptomatic hyperlactatemia may complicate nucleoside reverse-transcriptase inhibitor use. Females may be at increased risk for such complications. Our study evaluated the incidence of lactic acidosis and symptomatic hyperlactatemia by sex, analyzed clinical features, and described the safety of reintroducing highly active antiretroviral therapy (HAART) with zidovudine replacing stavudine. A retrospective cohort analysis was performed for 1735 adults (63% of whom were female) who initiated HAART from April 2004 through August 2005 in Soweto, South Africa, with follow-up until February 2006. Patients with lactate levels > or =4.5 mmol/L and no potential cause of elevated lactic acidosis other than receipt of HAART were included in the study. A total of 23 patients (22 of whom were female) experienced lactic acidosis. The overall incidence was 10.6 cases per 1000 patient-years; the incidence was 16.1 cases per 1000 patient-years in female patients and 1.2 cases per 1000 patient-years in male patients. Seven (30.4%) of the patients died. Eight (34.8%) of the patients were obese (body mass index [calculated as weight in kilograms divided by the square of height in meters], >30) at HAART initiation. Forty-four patients (37 of whom were female) had symptomatic hyperlactatemia. The overall incidence was 20.2 cases per 1000 patient-years, with an incidence of 27.0 cases per 1000 patient-years in female patients and 8.7 cases per 1000 patient-years in male patients. None of the patients died. Nine (20.4%) of the patients were obese at HAART initiation. Sixty-six of 67 patients were receiving stavudine, and 5 patients were receiving didanosine. Among 56 patients who restarted HAART with zidovudine for a cumulative nucleoside reverse-transcriptase inhibitor reexposure of 44.6 patient-years--including 41 patients who received treatment for > or =9 months--there were no relapses. Women in Soweto, South Africa, have a higher frequency of symptomatic hyperlactatemia and lactic acidosis than has been reported for patients in other study groups. In cases associated with stavudine use, restarting HAART with zidovudine seemed to be safe and effective for patients with limited nucleoside reverse-transcriptase inhibitor alternatives.