HAART Era Research Articles

Factors influencing cerebrospinal fluid and plasma HIV-1 RNA detection rate in patients with and without opportunistic neurological disease during the HAART era

BackgroundIn the central nervous system, HIV replication can occur relatively independent of systemic infection, and intrathecal replication of HIV-1 has been observed in patients with HIV-related and opportunistic neurological diseases. The clinical usefulness of HIV-1 RNA detection in the cerebrospinal fluid (CSF) of patients with opportunistic neurological diseases, or the effect of opportunistic diseases on CSF HIV levels in patients under HAART has not been well defined. We quantified CSF and plasma viral load in HIV-infected patients with and without different active opportunistic neurological diseases, determined the characteristics that led to a higher detection rate of HIV RNA in CSF, and compared these two compartments.MethodsA prospective study was conducted on 90 HIV-infected patients submitted to lumbar puncture as part of a work-up for suspected neurological disease. Seventy-one patients had active neurological diseases while the remaining 19 did not.ResultsHIV-1 RNA was quantified in 90 CSF and 70 plasma samples. The HIV-1 RNA detection rate in CSF was higher in patients with neurological diseases, in those with a CD4 count lower than 200 cells/mm3, and in those not receiving antiretroviral therapy, as well as in patients with detectable plasma HIV-1 RNA. Median viral load was lower in CSF than in plasma in the total population, in patients without neurological diseases, and in patients with toxoplasmic encephalitis, while no significant difference between the two compartments was observed for patients with cryptococcal meningitis and HIV-associated dementia. CSF viral load was lower in patients with cryptococcal meningitis and neurotoxoplasmosis under HAART than in those not receiving HAART.ConclusionDetection of HIV-1 RNA in CSF was more frequent in patients with neurological disease, a CD4 count lower than 200 cells/mm3 and detectable plasma HIV-1. Median HIV-1 RNA levels were generally lower in CSF than in plasma but some patients showed higher CSF levels, and no difference between these two compartments was observed in patients with cryptococcal meningitis and HIV-associated dementia, suggesting the presence of intrathecal viral replication in these patients. HAART played a role in the control of CSF HIV levels even in patients with cryptococcal meningitis and neurotoxoplasmosis in whom viral replication is potentially higher.

End-stage renal disease and chronic kidney disease in a cohort of African-American HIV-infected and at-risk HIV-seronegative participants followed between 1988 and 2004

HIV-infected African-Americans are at increased risk of end-stage renal disease requiring renal replacement therapy (RRT). To compare the incidence of RRT in HIV-infected and HIV-seronegative African-Americans and describe temporal trends in RRT and chronic kidney disease (CKD) in HIV infection. Cohort study in Baltimore including 4509 HIV-infected and 1746 HIV-seronegative African-Americans. Incident RRT was defined by matching participant identifiers with the US Renal Data System; CKD was defined as an estimated glomerular filtration rate < 60 ml/min per 1.73m for >/= 3 months. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated by indirect adjustment. Risk factors for RRT were assessed by person-time methods and Poisson regression. RRT was initiated in 24 HIV-seronegative subjects over 13 415 person-years of follow-up (SIR, 2.3; 95% CI, 1.5-3.4), in 51 HIV-infected participants without AIDS over 10 780 person-years (SIR, 6.9; 95% CI, 5.1-9.0), and in 125 participants with AIDS over 9833 person-years. SIR, 16.1; 95% CI, 13.4-19.2). In HIV-infected African-Americans, RRT incidences were 5.8 and 9.7/1000 person-years in the pre-HAART and HAART eras, respectively (adjusted rate ratio 1.2; 95% CI, 0.8-1.9). In supplementary analyses, CKD incidence declined significantly in the HAART era compared with pre-HAART, but the CKD period prevalence increased. Nearly 1% of HIV-infected African-Americans initiated RRT annually, a rate that was similar in the HAART and pre-HAART eras. While new cases of CKD decreased, the prevalence of CKD increased in the HAART era, primarily because survival in those with HIV-associated CKD has improved.

Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART

To analyse incidence and determinants of tuberculosis in HIV-seroconverters before and after the introduction of HAART. Data from a multicenter cohort study of 2238 HIV-seroconverters between the 1980s and 2004 were analysed and censored by December 2004. Calendar year at risk intervals were pre-1992, 1992-1996 and 1997-2004. Incident tuberculosis was calculated as cases per 1000 person-years (p-y). Survival analyses using Kaplan-Meier and multivariate Cox regression allowing for late-entry were used. Proportional hazards assumptions were checked with tests based on Schoenfeld residuals. Overall, 173 (7.7%) patients developed tuberculosis over 23 698 p-y at a rate of 7.3 cases per 1000 p-y [95% confidence interval (CI), 6.3-8.5]. Incident tuberculosis was higher in intravenous drug-users (IDUs), 12.3 per 1000 p-y compared with persons infected sexually, 3.8 per 1000 p-y (P < 0.001), and persons with clotting disorders (PCD), 2.7 per 1000 p-y (P < 0.001). A decreasing tuberculosis incidence trend was observed from 1995 in all categories. Highest tuberculosis rates, 44 per 1000 p-y, were observed prior to 1997 in IDUs infected with HIV for 11 years. In multivariable analyses women were less likely to develop tuberculosis [relative hazard (RH), 0.62; 95% CI, 0.41-0.96; P < 0.05) and IDUs were more likely to develop tuberculosis (RH, 3.0; 95% CI, 1.72-5.26, P < 0.001). In the HAART era, the hazard of developing tuberculosis was 70% lower (RH, 0.31; 95% CI, 0.17-0.54; P < 0.001). Before 1997, the risk of tuberculosis increased with time since HIV seroconversion, whereas it remained nearly constant in the HAART era. Since the mid-1990s important decreases in tuberculosis have been observed in HIV-seroconverters that probably reflect the impact of both HAART and tuberculosis control programmes.

HIV-Associated NK/T-Cell Lymphomas: A Review of 93 Cases.

Introduction: NK/T-cell lymphomas (NKTCL) are being reported with increased frequency in HIV-infected patients in the HAART era. However, there has been no comprehensive review of these emerging HIV-associated lymphomas. We present, to our knowledge, the first comprehensive review of the epidemiology, clinical and pathologic features, therapeutic options, and outcome in HIV-associated NKTCL.Methods: A total of 93 cases of NKTCL in HIV-infected individuals were identified in a literature review using PubMed and cited articles from 1996 until March 2007. Data regarding epidemiology (country), demographics (age, gender), clinical features (presentation, tumor location), HIV status (CD4, AIDS-defining illness, coinfections), lymphoma (WHO/EORTC subtype, immunophenotype, Ann Arbor stage), treatment, and outcome were extracted.Results: Cases were reported worldwide (USA, Europe, South America, Asia), with a 15x increased incidence compared to the general population. Patients were of median age 38 years (range 1–63) at presentation, exhibited a 4:1 male predominance, and had a median CD4 count of 184 cells/mm3. Up to 54% had a prior AIDS-defining illness. The most common clinical findings were lymphadenopathy, B symptoms, erythroderma and pruritus. All subtypes were noted including Peripheral T-cell (n=36), Cutaneous T-cell including Mycosis fungoides (n=25), Anaplastic Large Cell (n=13), Adult T-cell Leukemia/Lymphoma (n=8), NK cell (n=4), and other lymphomas (2 AILD, 2 Enteropathy-associated, 1 PEL, 1 Intravascular). Most expressed CD45RO and CD3 antigens, CD4>CD8, CD30 in a subset (n=23), and EBV was detected in 20 cases (mainly extranodal PTCL, cutaneous ALCL, and NK cells). Most (74%) were extranodal (50% involving skin) and 26% nodal. Staging (60 patients) overall showed stage I (27%), II (3%), III (17%), and IV (53%).There was no standard therapeutic approach, with 46% given one modality, 17% multimodal treatment, and 12% were untreated in reported cases. HAART was rarely used. Death occurred in 55% of patients and median overall survival (83 patients) was 1.1 years from the time of diagnosis.Conclusions: NKTCL afflicted HIV-infected persons are likely to be young males with AIDS who have a CD4 count under 200 cells/mm3 at presentation. They are also prone to present with extranodal disease, skin involvement, and at an advanced stage. Although a standard treatment approach is still required, the prognosis of HIV-associated NKTCL remains poor. The role of HAART needs to be further explored.

Visceral leishmaniasis and HIV infection in the HAART era

Visceral Leishmaniasis is an endemic infection in Portugal, as well as in other Mediterranean basin countries, where it has become a frequent complication of HIV infection. There are several studies published about Leishmania/HIV co-infection, however some particularities of its epidemiology, pathogenesis and especially of its treatment and prophylaxis remain unclear and undefined. The authors review some aspects of this co-infection, particularly epidemiology, clinical classic manifestations and laboratory features, diagnosis, treatment, prophylaxis and prevention and report the casuistic of the Infectious Diseases Department of the University Hospital of Coimbra during the last ten years (1996-2006) in the HAART (<<highly active antiretroviral therapy>>) era. Visceral Leishmaniasis behaves as an opportunistic infection in HIV-infected patients and should be considered as an AIDS-defining disease. Nowadays and according to World Health Organization, VL is the second most important protozoan disease and one of the most neglected; therefore the establishment of treatment and prophylaxis guidelines is urgent.

Host–microbe interplay in persistent Staphylococcus aureus nasal carriage in HIV patients

It has been shown that persistent Staphylococcus aureus nasal carriage results in increased bacterial dispersal and a higher risk of infection compared to non-or-intermittent S. aureus carriage. Although many studies investigated S. aureus nasal carriage in HIV patients, none compared persistent carriage to non-persistent carriage nor were studies performed in the HAART era. We investigated the host–microbe interplay of persistent S. aureus nasal carriage in HIV-infected patients by studying host determinants of persistent carriage as well as the genetic structure of S. aureus strains isolated. We compared this genetic structure with the previously determined population structure of S. aureus isolates obtained from healthy individuals. Between February 2004 and June 2005 all HIV patients visiting the outpatient department of Erasmus MC (Rotterdam, The Netherlands) were asked to participate in this study. Participants were interviewed and screened for persistent S. aureus carriage using two semi-quantitative nasal swab cultures. For 443 patients two cultures were available, 131 (29.6%) were persistent carriers, which is significantly higher as compared to healthy individuals from the same geographic region (17.6%; P < 0.0001). Male sex (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.32–3.73), current smoking (OR, 0.58; 95% CI, 0.38–0.90), Pneumocystis jiroveci pneumonia (PCP) prophylaxis (OR, 0.39; 95% CI, 0.16–0.97) and antiretroviral therapy (OR, 0.61; 95% CI, 0.38–0.98) were independent determinants of persistent carriage. Only two strains were mecA positive (1.2%) and no PVL positive strains were detected. The population structure of S. aureus strains isolated from HIV patients appeared to be strongly overlapping with that of S. aureus isolates from healthy individuals.

Risks factors of liver fibrosis in a cohort of intravenous drug users coinfected with HIV and HCV at the HAART era: the role of mixed steatosis: Fibrosis factors in HIV / HCV intravenous drug users

Factors associated with the occurrence of severe liver fibrosis in HIV/HCV (hepatitis C virus) coinfected patients remain poorly understood. We thus questioned which factors influenced the occurrence of fibrosis in a cohort of HIV/HCV coinfected intravenous drug user patients. HIV/HCV coinfected intravenous drug user patients naive of anti-HCV therapy for whom a liver biopsy was performed between 1996 and 2003 were retrospectively studied in three University hospitals in Paris and the Parisian region. One hundred and fifty two patients (131 men and 21 women; mean age 39.3+/-4.9 years) were studied. Most of them (62%) were treated with HAART. HCV genotypes included type 1 (N=78), type 2 (N=1), type 3 (N=38) and type 4 (N=35). Mean duration of HCV infection was 19.0+/-5.2 years. Sixty-six percent had minimal to moderate fibrosis (F0/F1/F2) and 34% severe fibrosis (F3/F4). Multivariate analysis retained METAVIR activity score (OR=2.60, 95%CI [1.46-4.64]; P=0.001), mixed pattern of steatosis (OR=3.29, 95%CI [1.24-8.71]; P=0.017) and a CD4 cell count<200/mm3 (OR=4.04, 9%CI [1.47-11.12]; P=0.007) as independent factors associated with severe fibrosis. HAART did not influence the occurrence of liver fibrosis. In this cohort of HIV/HCV coinfected intravenous drug user patients, METAVIR activity score, mixed steatosis and a low CD4 cell count were independent factors associated with severe liver fibrosis.

The prevalence and incidence of neurocognitive impairment in the HAART era

HAART suppresses HIV viral replication and restores immune function. The effects of HAART on neurological disease are less well understood. The aim of this study was to assess the prevalence and incidence of neurocognitive impairment in individuals who initiated HAART as part of an AIDS clinical trial. A prospective cohort study of HIV-positive patients enrolled in randomized antiretroviral trials, the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. We examined the association between baseline and demographic characteristics and neurocognitive impairment among 1160 subjects enrolled in the ALLRT study. A history of immunosuppression (nadir CD4 cell count < 200 cells/microl) was associated with an increase in prevalent neurocognitive impairment. There were no significant virological and immunological predictors of incident neurocognitive impairment. Current immune status (low CD4 cell count) was associated with sustained prevalent impairment. The association of previous advanced immunosuppression with prevalent and sustained impairment suggests that there is a non-reversible component of neural injury that tracks with a history of disease progression. The association of sustained impairment with worse current immune status (low CD4 cell count) suggests that restoring immunocompetence increases the likelihood of neurocognitive recovery. Finally, the lack of association between incident neurocognitive impairment and virological and immunological indicators implies that neural injury continues in some patients regardless of the success of antiretroviral therapy on these laboratory measures.

HAD and the need for new trial design methodology

The study by Schifitto et al. in this issue raises important points in relation to AIDS dementia complex – now known as HIV associated dementia (HAD) – and its less severe forms of minor and asymptomatic neurocognitive impairment. These new terms are the result of a consensus working group convened under the auspices of the National Institutes of Mental Health to reappraise HAD in the HAART era. Schifitto et al. conducted a randomized double-blind placebo controlled trial of adding memantine, a weak N-methyl D-aspartate receptor antagonist, to stable background HAART in HAD patients. Unfortunately, there was no benefit at week 16 although at week 20, in the washout period off the drug, there was some evidence of benefit. In general, the Schifitto et al. paper raises issues related to the importance of HAD itself in the context of HAART and methodological issues associated with clinical trials of novel agents in HAD. This journal is to be lauded for its decision to publish the study despite its negative results.

AIDS-associated central nervous system cryptococcosis: a Brazilian case study

In recent years the effect of HAART in patients with AIDS has been great at decreasing the incidence of opportunistic infections. Nonetheless, patients with AIDS living in developing countries still present with severe central nervous system cryptococcosis, with high mortality rates. The study of the clinical-epidemiological-laboratory aspects of the patients treated before the HAART era might be useful in an assessment of the impact of these drugs in the prognosis of cases.

Evolution of Cervical Cytologic Changes among HIV-Infected Women with Normal Cytology in the HAART Era

The influence of HAART on the evolution to cervical squamous intraepithelial lesions (SIL) among HIV(+) women with a normal cytological test in the HAART era was studied. A retrospective cohort study (1997-2005) of HIV-infected women treated with HAART was conducted. Those with a normal cervical cytology (Papanicolaou test) and at least one subsequent test were included. Survival (time until diagnosis of SIL), univariate, and multivariate analyses were performed. A total of 133 HIV-infected patients treated with HAART were included. The incidence of SIL was 35% (47 patients). SIL was diagnosed in 36 of 110 (33%) patients with a baseline and final immunological status of >200 CD4 cells/microl and in 6 of 9 (67%) patients with a baseline and final immunological status of < or =200 CD4 (OR: 0.24, 95% CI: 0.06-1.03, p = 0.041). SIL was diagnosed in 10 of 60 (17%) patients with an undetectable baseline and final HIV viral load and in 36 of 70 (51%) patients with a detectable HIV viral load (OR: 0.19, 95% CI: 0.07-0.46, p < 0.001). A high incidence of SIL (cancer precursor lesions) was observed among HIV(+) women without a background of cervical pathology. The effect of HAART on the control of HIV replication and of immunological status (>200 CD4) through the follow-up was associated with a reduction of SIL.

Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART

The introduction of HAART has decreased mortality and progression to AIDS in perinatally HIV-1-infected children, but information on modification of the rate of specific clinical events is limited. An observational population study on changes in HIV-1-related morbidity was conducted on 1402 perinatally HIV-1-infected children enrolled in the Italian Register for HIV Infection in Children and prospectively followed in the pre-HAART (1985-1995) and post-HAART periods (1996-2000, and 2001-2005). Of this group, 773 children (55.1%) were followed from birth. Median observation time was 8.58 years (interquartile range, 3.71-13.72). Overall, 666 (47.5%) children developed AIDS and 420 (29.9%) died. Improved survival over time was evidenced at Kaplan-Meier analysis (P < 0.0001). Poisson regression analysis indicated that Centers for Disease Control and Prevention class B and C clinical event rates and most of the HIV-1-related organ complication rates significantly decreased starting from 1996-2000. Significant reductions in rates of cancer and opportunistic infections were evidenced after 2000. Nevertheless, opportunistic infections still occurred at high rates (6.09/100 person-years) in 2001-2005, with high rate of bacterial infections (3.55/100 person-years), particularly pneumonia (1.66/100 person-years), in this period. CD4 cell percentage was > 15% in 58.5% children with pneumonia. Progressive reductions of both mortality and rates of class B and C clinical events, including organ complications, were evidenced in the HAART era. Nevertheless, severe bacterial infections, particularly pneumonia, still occurred at considerable high rates, even in the absence of a severe CD4 cell depletion.

Dietary fat intake and relationship to serum lipid levels in HIV-infected patients with metabolic abnormalities in the HAART era

To evaluate dietary intake and its relationship to lipid parameters in HIV-infected patients with metabolic abnormalities. We prospectively determined dietary intake (4-day food records or 24-h recall) in 356 HIV-infected patients and 162 community-derived HIV-negative controls evaluated for metabolic studies between 1998-2005. Differences in dietary intake between HIV-infected patients and non-HIV-infected controls, in relation to the established 2005 USDA (United States Department of Agriculture) Recommended Dietary Guidelines, were determined. The relationship between dietary fat intake and serum lipid levels among HIV-infected individuals was also evaluated. Assessment of dietary intake in this group of HIV-infected patients demonstrated increased intake of total dietary fat (P < 0.05), saturated fat (P = 0.006), and cholesterol (P = 0.006) as well as a greater percentage of calories from saturated fat (P = 0.002) and from trans fat (P = 0.02), despite similar caloric intake to the control individuals. A significantly higher percentage of HIV-infected patients were above the 2005 USDA Recommended Dietary Guidelines for saturated fat (> 10%/day) (76.0% HIV vs. 60.9% controls, P = 0.003), and cholesterol (> 300 mg/day) (49.7% HIV vs. 37.9% controls, P = 0.04). Saturated fat intake was strongly associated with triglyceride level [triglyceride level increased 8.7 mg/dl (parameter estimate) per gram of increased saturated fat intake, P = 0.005] whereas total fat was inversely associated with triglyceride level [triglyceride level decreased 3.0 mg/dl (parameter estimate) per gram of increased total fat intake, P = 0.02] among HIV-infected individuals. Increased intake of saturated fat is seen and contributes to hypertriglyceridemia among HIV-infected patients who have developed metabolic abnormalities. Increased saturated fat intake should be targeted for dietary modification in this population.

Improving the representativeness of behavioral and clinical surveillance for persons with HIV in the United States: the rationale for developing a population-based approach.

The need for a new surveillance approach to understand the clinical outcomes and behaviors of people in care for HIV evolved from the new challenges for monitoring clinical outcomes in the HAART era, the impact of the epidemic on an increasing number of areas in the US, and the need for representative data to describe the epidemic and related resource utilization and needs. The Institute of Medicine recommended that the Centers for Disease Control and Prevention and the Heath Resources and Services Administration coordinate efforts to survey a random sample of HIV-infected persons in care, in order to more accurately measure the need for prevention and care services. The Medical Monitoring Project (MMP) was created to meet these needs. This manuscript describes the evolution and design of MMP, a new nationally representative clinical outcomes and behavioral surveillance system, and describes how MMP data will be used locally and nationally to identify care and treatment utilization needs, and to plan for prevention interventions and services.

Predictors of Influenza Vaccination in HIV‐Infected Patients in the United States, 1990–2002

Although annual influenza vaccination of human immunodeficiency virus (HIV)-infected patients has been recommended in the United States since the early 1990s, vaccine coverage in this population is reported to be low. The objectives of the present study were to assess trends in influenza vaccination coverage in HIV-infected patients and to determine predictors of influenza vaccination. We analyzed data from the medical records of 51,021 HIV-infected patients from 10 US cities observed in a longitudinal cohort study between 1990 and 2002. Using multivariate logistic regression, we determined predictors of influenza vaccination for both the pre-highly active antiretroviral therapy (HAART) and HAART eras. Vaccination coverage increased from 28.5% in the 1990 to 41.6% in the 2002 influenza season. Vaccine coverage increased with increasing age and frequency of medical visits. In the HAART era, persons prescribed antiretroviral therapy were more likely and those with higher viral loads and lower CD4 T cell counts were less likely to have received influenza vaccine. Although influenza vaccination coverage in this population has increased in recent years, it is well below the Healthy People 2010 target of 60%. Efforts should be undertaken to increase influenza vaccination in HIV-infected persons.

Cetuximab/Targeted Chemotherapy in an HIV-Positive Patient with Metastatic Colorectal Cancer in the HAART Era: a Case Report

Recent data have shown the efficacy of cetuximab/Folfiri regimen in patients with chemotherapy-resistant metastatic colorectal cancer. In the literature there are no data about this treatment in HIV-positive patients with metastatic colorectal cancer. At the Aviano Cancer Center, we used the cetuximab/Folfiri regimen and concomitant HAART in an HIV-positive patient with metastatic colorectal cancer. The patient experienced acceptable non-hematological toxicity, without any opportunistic infection and his HIV infection was kept under control. This case suggests that, in the HAART era, a multidisciplinary approach can be offered to HIV patients with advanced cancer when they have good performance status, resulting in efficacious control of the HIV infection.

First Italian Consensus Statement on Diagnosis, Prevention and Treatment of Cardiovascular Complications in HIV-infected Patients in the HAART Era (2006)

The present document contains recommendations for assessment, prevention and treatment of cardiovascular risk for HIV-infected patients. All recommendations were graded according to the strength and quality of the evidence and were voted on by 73 members of the Italian Cardiovascular Risk Guidelines Working Group which includes both experts in HIV/AIDS care and in cardiovascular and metabolic medicine. Since antiretroviral drug exposure represents only one risk factor, continued emphasis on an integrated management is given. This should include prevention and treatment of known cardiovascular risk factors (such as dyslipidaemia, diabetes, insulin resistance, healthy diet, physical activity, avoidance of smoking), but also rational switch of antiretroviral drugs. A rational switch strategy should consider both metabolic and anthropometric disturbances and effectiveness of antiretroviral regimens.

Popular Use of Traditional Chinese Medicine in HIV Patients in the HAART era

Seventy-six Chinese male HIV patients were interviewed on their use of traditional Chinese medicine (TCM). All except one had undetectable viral load, 28 had already progressed to AIDS. Forty-five (59.2%) had used TCM--11 infrequently and 33 commonly. No specific TCM recipe was preferentially used, while a variety of herbal tea and other over-the-counter health products of TCM in origin were reported. A minority (28.9%) have consulted a TCM practitioner in the preceding 6 months. Most patients admitted using TCM for the treatment of minor ailments (60.0%) and general health maintenance (57.8%), while western medicine was chosen for the therapy of major medical illnesses. TCM did not seem to have significant influence on the conventional HAART in this cohort. Many used TCM at a time interval from HAART in order not to affect the latter's effectiveness.

Twin pregnancy as a risk factor for mother-to-child transmission of HIV-1: trends over 20 years

We investigated whether twin pregnancies were at increased risk of mother-to-child HIV-1 transmission (MTCT), in comparison with singletons. Among HIV-1 infected women enrolled in the French Perinatal HIV Cohort (n = 9262), we studied the association between twin deliveries and MTCT rate according to three time periods (pre-1994, 1994-1996, 1997-2004) and the effect of birth order. The mother was considered to have transmitted if at least one of the twins was infected. Univariate and multivariate analyses of risk factors for MTCT were performed for deliveries in the periods up to 1996. Overall, 2.1% (192/9262) of all the deliveries were twins. The rate of prematurity was greater in twins than in singletons (54% and 13%, respectively). Up to 1996 the rate of MTCT of HIV-1 was 28.3% (15/53) in twin pregnancies, versus 13.5% (414/3077) in singletons [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.4-4.7; P = 0.002; adjusted OR, 2.3: 95% CI, 1.1-2.3; P = 0.03). In the period from 1997 to 2003, MTCT was low and did not differ between twins (1.0%) and singletons (1.8%; P = 1.0). Overall, the transmission rate for the first-born child was threefold that for the second-born child (14/164, 8.5% versus 4/164, 2.4%; P = 0.008). Twin pregnancies were at increased risk of transmission, but in the era of HAART this risk was reduced for twins, as well as singletons. Management of multiple pregnancies should take into account the risks of premature rupture of the membranes and preterm delivery.

A further investigation of health-related quality of life over time among men with HIV infection in the HAART era

This is the third study in a line of research which is designed to increase scientific understanding of the predictors of health-related quality of life (HRQOL) among men with HIV infection using data collected in large, prospective cohort study. Building on two prior investigations, this study examined the time-dependent relationships of psychosocial and clinical variables (active coping strategies, social support, CD4 cell count, comorbidity, and duration of HIV infection) and 10 HRQOL dimensions at two time points (baseline and 12 months). Using linear mixed models, we found that most relationships between the psychosocial and clinical variables and HRQOL dimensions were consistent across time. However, there were interactions between time and CD4 cell count and some HRQOL dimensions. Specifically, increased active coping and social support were positively related, whereas more comorbid conditions and longer HIV infection duration were negatively related with multiple HRQOL dimensions at both baseline and 12 months. CD4 cell count was positively associated with emotional well-being at both time points, but the associations between CD4 cell count and five HRQOL dimensions were negative at baseline but positive at 12 months. These findings provide additional support for the recommendation that clinicians and health planners should continually strive to enhance active coping strategies and social support, manage comorbid conditions, and incorporate duration of HIV diagnoses in their treatment plans. Because the relationships between CD4 cell count and HRQOL dimensions varied over time, it is important to recognize that results from laboratory tests (i.e., CD4 cell count) may have differential quality of life implications for patients at various times in their disease trajectories.