Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Cost-effectiveness of single-dose AmBisome pre-emptive treatment for the prevention of cryptococcal meningitis in African low and middle-income countries.

Cryptococcal antigen (CrAg) screening is recommended for patients with advanced HIV to reduce AIDS-related mortality. For asymptomatic CrAg-positive persons, fluconazole pre-emptive therapy is standard, despite a ∼25% failure rate. Single-dose liposomal amphotericin B (AmBisome) is non-inferior to standard treatment for cryptococcal meningitis. We evaluate the threshold of efficacy necessary for AmBisome + fluconazole to be cost-effective as pre-emptive therapy for CrAg-positive persons.We created a decision analytic model to evaluate CrAg screening and treatment in HIV-infected persons with CD4 < 100 cells/µL. Costs were estimated for screening, pre-emptive therapy, and hospitalization for an example low-income country (Uganda) and middle-income country (South Africa). We used a discounted price range of AmBisome® at ${\$}$16.25 to ${\$}$40 per 50 mg vial for both Uganda and South Africa. We estimated AmBisome efficacy from 75 to 95%. Parameter assumptions were based on prospective CrAg screening studies and clinical trials in Africa. Disability adjusted life years (DALYs) were calculated using the age-specific life expectancy in Uganda, per WHO Global Health Observatory data. We modeled the theoretical efficacy of adjunctive AmBisome to determine cost per DALY averted.In South Africa, at ${\$}$16.25 per vial cost and a minimum efficacy of 85%, adjunctive AmBisome is cost-saving compared to fluconazole monotherapy. Compared to fluconazole pre-emptive therapy in Uganda, AmBisome + fluconazole would cost ${\$}$475, ${\$}$220, or ${\$}$136 per DALY averted if meningitis-free survival efficacy was 80, 85, or 90% at ${\$}$24 per vial cost.Investing in AmBisome may be cost-effective in low-income settings compared to using fluconazole pre-emptive therapy alone, if efficacy is 85% or greater. AmBisome pre-emptive therapy appears more cost-efficient in middle-income settings where hospitalization costs for meningitis, and GDP per capita are higher. LAY SUMMARY: We evaluate the efficacy necessary for AmBisome + fluconazole to be cost-effective to prevent cryptococcal meningitis. We found that if AmBisome pre-emptive therapy has an efficacy of 85% or greater, it is likely to be cost-effective in low-income settings.

Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.

OBJECTIVES: The introduction of two new non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the past 5 years and the identification of novel NNRTI-associated mutations have made it necessary to reassess the extent of phenotypic NNRTI cross-resistance. METHODS: We analysed a dataset containing 1975, 1967, 519 and 187 genotype-phenotype correlations for nevirapine, efavirenz, etravirine and rilpivirine, respectively. We used linear regression to estimate the effects of RT mutations on susceptibility to each of these NNRTIs. RESULTS: Sixteen mutations at 10 positions were significantly associated with the greatest contribution to reduced phenotypic susceptibility (≥10-fold) to one or more NNRTIs, including: 14 mutations at six positions for nevirapine (K101P, K103N/S, V106A/M, Y181C/I/V, Y188C/L and G190A/E/Q/S); 10 mutations at six positions for efavirenz (L100I, K101P, K103N, V106M, Y188C/L and G190A/E/Q/S); 5 mutations at four positions for etravirine (K101P, Y181I/V, G190E and F227C); and 6 mutations at five positions for rilpivirine (L100I, K101P, Y181I/V, G190E and F227C). G190E, a mutation that causes high-level nevirapine and efavirenz resistance, also markedly reduced susceptibility to etravirine and rilpivirine. K101H, E138G, V179F and M230L mutations, associated with reduced susceptibility to etravirine and rilpivirine, were also associated with reduced susceptibility to nevirapine and/or efavirenz. CONCLUSIONS: The identification of novel cross-resistance patterns among approved NNRTIs illustrates the need for a systematic approach for testing novel NNRTIs against clinical virus isolates with major NNRTI-resistance mutations and for testing older NNRTIs against virus isolates with mutations identified during the evaluation of a novel NNRTI.

Clinic-based SAMBA-II vs centralized laboratory viral load assays among HIV-1 infected children, adolescents and young adults in rural Zimbabwe: A randomized controlled trial.

BACKGROUND: In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH. METHODS: The study was registered on ClinicalTrials.gov: NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (1:1) to 6 monthly VL monitoring by COBAS®Ampliprep®/Taqman48® HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months. RESULTS: Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7-18.2) and 6.4 (3.7-7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ≥1,000 copies/ml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p = 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1-4.4) vs 4.5 (3.5-6.3) respectively; p = 0.027 at 12 months. Drug switching was documented among 26/347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9-10.0) months vs 4.4 (2.5-8.4) respectively; p = 0.569). Out of 24 confirmed second-line failures, only 4/19 (21%) had protease inhibitor resistance. CONCLUSION: In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH.

Standardized comparison of the relative impacts of HIV-1 reverse transcriptase (RT) mutations on nucleoside RT inhibitor susceptibility.

Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV drug resistance. Furthermore, the NRTIs have highly variable dynamic susceptibility ranges, making it difficult to determine the relative effect of an RT mutation on susceptibility to different NRTIs. In this study, we analyzed 1,273 genotyped HIV-1 isolates for which phenotypic results were obtained using the PhenoSense assay (Monogram, South San Francisco, CA). We used a parsimonious feature selection algorithm, LASSO, to assess the possible contributions of 177 mutations that occurred in 10 or more isolates in our data set. We then used least-squares regression to quantify the impact of each LASSO-selected mutation on each NRTI. Our study provides a comprehensive view of the most common NRTI resistance mutations. Because our results were standardized, the study provides the first analysis that quantifies the relative phenotypic effects of NRTI resistance mutations on each of the NRTIs. In addition, the study contains new findings on the relative impacts of thymidine analog mutations (TAMs) on susceptibility to abacavir and tenofovir; the impacts of several known but incompletely characterized mutations, including E40F, V75T, Y115F, and K219R; and a tentative role in reduced NRTI susceptibility for K64H, a novel NRTI resistance mutation.

Utilization of psychiatric services among low-income HIV-infected patients with psychiatric comorbidity.

INTRODUCTION: HIV-infected individuals face a tremendous burden of psychiatric comorbidity. This study evaluates a community health care system's effort to screen for psychiatric disorders among patients at an HIV clinic and evaluate adherence to psychiatric service utilization. METHODS: Standardized screening measures were used to identify participants who met diagnostic symptom criteria for post-traumatic stress disorder (PTSD), acute stress disorder (ASD) and depression. All participants who screened positive were referred for psychiatric follow-up. Rates of utilization were measured and barriers to adherence were investigated. RESULTS: Of the 210 participants, 118 patients met screening criteria for PTSD, ASD, and/or depression, and 116 of these had medical records available for review. Of the 116 patients with psychiatric comorbidity, 46.6% saw a psychiatrist and/or were prescribed a psychiatric medication. Thirty-two percent of Latinos, 40.5% of African Americans, and 38.5% of heterosexuals utilized referred psychiatric services, and these rates were significantly less than their counterparts. One hundred patients were seen by a social worker. DISCUSSION: While a large burden of psychiatric comorbidity exists among this population of HIV-positive patients, only half adhered to recommended psychiatric services referrals. Further research is warranted to examine cost-effective interventions to maximize psychiatric screening, referral, and follow-up with mental health services in this vulnerable population.

Viral load care of HIV-1 infected children and adolescents: A longitudinal study in rural Zimbabwe.

INTRODUCTION: Maintaining virologic suppression of children and adolescents on ART in rural communities in sub-Saharan Africa is challenging. We explored switching drug regimens to protease inhibitor (PI) based treatment and reducing nevirapine and zidovudine use in a differentiated community service delivery model in rural Zimbabwe. METHODS: From 2016 through 2018, we followed 306 children and adolescents on ART in Hurungwe, Zimbabwe at Chidamoyo Christian Hospital, which provides compact ART regimens at 8 dispersed rural community outreach sites. Viral load testing was performed (2016) by Roche and at follow-up (2018) by a point of care viral load assay. Virologic failure was defined as viral load ≥1,000 copies/ml. A logistic regression model which included demographics, treatment regimens and caregiver's characteristics was used to assess risks for virologic failure and loss to follow-up (LTFU). RESULTS: At baseline in 2016, 296 of 306 children and adolescents (97%) were on first-line ART, and only 10 were receiving a PI-based regimen. The median age was 12 years (IQR 8-15) and 55% were female. Two hundred and nine (68%) had viral load suppression (<1,000 copies/ml) and 97(32%) were unsuppressed (viral load ≥1000). At follow-up in 2018, 42/306 (14%) were either transferred 23 (7%) or LTFU 17 (6%) and 2 had died. In 2018, of the 264 retained in care, 107/264 (41%), had been switched to second-line, ritonavir-boosted PI with abacavir as a new nucleotide analog reverse transcriptase inhibitor (NRTI). Overall viral load suppression increased from 68% in 2016 to 81% in 2018 (P<0.001). CONCLUSION: Viral load testing, and switching to second-line, ritonavir-boosted PI with abacavir significantly increased virologic suppression among HIV-infected children and adolescents in rural Zimbabwe.

Single-cell, phosphoepitope-specific analysis demonstrates cell type- and pathway-specific dysregulation of Jak/STAT and MAPK signaling associated with in vivo human immunodeficiency virus type 1 infection.

Despite extensive evidence of cell signaling alterations induced by human immunodeficiency virus type 1 (HIV-1) in vitro, the relevance of these changes to the clinical and/or immunologic status of HIV-1-infected individuals is often unclear. As such, mapping the details of cell type-specific degradation of immune function as a consequence of changes to signaling network responses has not been readily accessible. We used a flow cytometric-based assay of signaling to determine Janus kinase/signal transducers and activators of transcription (Jak/STAT) signaling changes at the single-cell level within distinct cell subsets from the primary immune cells of HIV-1-infected donors. We identified a specific defect in granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven Stat5 phosphorylation in the monocytes of HIV-1+ donors. This inhibition was statistically significant in a cohort of treated and untreated individuals. Ex vivo Stat5 phosphorylation levels varied among HIV-1+ donors but did not correlate with CD4(+) T-cell counts or HIV-1 plasma viral load. Low Stat5 activation occurred in HIV-1-infected donors despite normal GM-CSF receptor levels. Investigation of mitogen-activated protein kinase (MAPK) pathways, also stimulated by GM-CSF, led to the observation that lipopolysaccharide-stimulated extracellular signal-regulated kinase phosphorylation is enhanced in monocytes. Thus, we have identified a specific, imbalanced monocyte signaling profile, with inhibition of STAT and enhancement of MAPK signaling, associated with HIV-1 infection. This understanding of altered monocyte signaling responses that contribute to defective antigen presentation during HIV-1 infection could lead to immunotherapeutic approaches that compensate for the deficiency.

Combining Phylogenetic and Network Approaches to Identify HIV-1 Transmission Links in San Mateo County, California.

The HIV epidemic in San Mateo County is sustained by multiple overlapping risk groups and is an important hub for HIV transmission in northern California. Limited access to care has led historically to delayed clinical presentation, higher rates of opportunistic infections, and an increased prevalence of antiretroviral drug resistance. The virologic and clinical consequences of treatment within these multiple ethnic and behavioral groups are poorly understood, highlighting the need for efficient surveillance strategies that are able to elucidate transmission networks and drug resistance patterns. We obtained sequence data from a group of 316 HIV-positive individuals in the San Mateo AIDS Program over a 14-year period and integrated epidemiologic, phylogenetic, and network approaches to characterize transmission clusters, risk factors and drug resistance. Drug resistance mutations were identified using the Stanford HIV Drug Resistance Database. A maximum likelihood tree was inferred in RAxML and subjected to clustering analysis in Cluster Picker. Network analysis using pairwise genetic distances was performed in HIV-TRACE. Participants were primarily male (60%), white Hispanics and non-Hispanics (32%) and African American (20.6%). The most frequent behavior risk factor was male-male sex (33.5%), followed by heterosexual (23.4%) and injection drug use (9.5%). Nearly all sequences were subtype B (96%) with subtypes A, C, and CRF01_AE also observed. Sequences from 65% of participants had at least one drug resistance mutation. Clustered transmissions included a higher number of women when compared to non-clustered individuals and were more likely to include heterosexual or people who inject drugs (PWID). Detailed analysis of the largest network (N = 47) suggested that PWID played a central role in overall transmission of HIV-1 as well as bridging men who have sex with men (MSM) transmission with heterosexual/PWID among primarily African American men. Combined phylogenetic and network analysis of HIV sequence data identified several overlapping risk factors in the epidemic, including MSM, heterosexual and PWID transmission with a disproportionate impact on African Americans and a high prevalence of drug resistance.

Screening and management of viral hepatitis and hepatocellular carcinoma in Mongolia: results from a survey of Mongolian physicians from all major provinces of Mongolia.

BACKGROUND: According to Globocan, Mongolia has the highest worldwide hepatocellular carcinoma (HCC) incidence (78.1/100 000, 3.5× higher than China). AIMS AND METHODS: We conducted an anonymous survey of physicians from major provinces who attended an educational liver symposium, analysing their demography, practice, knowledge, perceptions and proposed solutions. Multivariate logistic regression was used to estimate OR relating demography and practice factors with higher provider knowledge and improvement. RESULTS: Of the 121 attendees, 44-95 (36-79%) responded to each question. Most were female (87%), young (79% age <50), subspecialists (81%), university-affiliated (74%), and practised in urban areas (61%). The mean pretest and post-test scores per physician were 60.4±20.4 and 65.6±21.3, with no observed significant predictors for baseline knowledge or improvement. Most (>80%) noted that <50% of patients who need hepatitis or HCC screening receive it. The main perceived barriers to screening were inability to pay for tests, lack of guidelines and poor patient awareness. Hepatitis treatment rates were low; 83% treated hepatitis C virus in <10 patients in the past year, and 86% treated hepatitis B virus in <10 patients/month. Treatment barriers were multifactorial, with cost as a principal barrier. Proposed solutions were universal screening policies (46%), removal of financial barriers (28%) and provider education (20%). CONCLUSIONS: Physicians from major regions of Mongolia noted low screening for viral hepatitis, even lower treatment rates, financial barriers and the need for increased educational efforts. We advocate broad-based medical education tailored to local needs and based on needs assessment and outcome measurements.

Social support and maladaptive coping as predictors of the change in physical health symptoms among persons living with HIV/AIDS.

This study examined social support and maladaptive coping as predictors of HIV-related health symptoms. Sixty-five men and women living with HIV/AIDS completed baseline measures assessing coping strategies, social support, and HIV-related health symptoms. The sample was primarily low-income and diverse with respect to gender, ethnicity, and sexual orientation. Three, 6, and 12 months after completing baseline assessments, physical health symptoms associated with HIV disease were assessed. After controlling for demographic characteristics, CD4 T-cell count, and baseline HIV-related health symptoms, individuals reporting lower increase in HIV-related health symptoms used less venting (expressing emotional distress) as a strategy for coping with HIV. However, when satisfaction with social support was added to the model, the use of this coping strategy was no longer significant, and individuals reporting more satisfying social support were more likely to report lower increase in their HIV-related health symptoms, suggesting that social support is a robust predictor of health outcomes over time independent of coping style and baseline medical status. These findings provide further evidence that social support can buffer deleterious health outcomes among individuals with a chronic illness. Future research needs to examine mediating pathways that can explain this relationship.

HIV drug resistance mutations in proviral DNA from a community treatment program.

BACKGROUND: Drug resistance mutations archived in resting memory CD4+ cells may persist despite suppression of HIV RNA to <50 copies/ml. We sequenced pol gene from proviral DNA among viremic and suppressed patients to identify drug resistance mutations. METHODS: The Peninsula AIDS Research Cohort study enrolled and followed over 2 years 120 HIV infected patients from San Mateo and San Francisco Counties. HIV-1 pol genotyping by bulk sequencing was performed on 38 DNA and RNA from viremic patients and DNA only among 82 suppressed patients at baseline. Antiretroviral susceptibility was predicted by HIVDB.stanford.edu. RESULTS: Among 120 subjects, 81% were on antiretroviral therapy and had been treated for a median time of 7 years. Thirty-two viremic patients showed concordant RNA and DNA genotypes (84%); the discordant profiles were mainly observed in patients with low-level viremia. Among suppressed patients, 21 had drug resistance mutations in proviral DNA (26%) with potential resistance to one, two or three ARV classes in 16, 4 and 1 samples respectively. CONCLUSIONS: The high level of genotype concordance between DNA and RNA in viremic patients suggested that DNA genotyping might be used to assess drug resistance in resource-limited settings, and further investigation of extracted DNA from dried blood spots is needed. Drug resistance mutations in proviral DNA in 26% of subjects with less than 50 copies/ml pose a risk for the transmission of drug resistant virus with virologic failure, treatment interruption or decreased adherence.

Do clinical decision-support reminders for medical providers improve isoniazid preventative therapy prescription rates among HIV-positive adults? Study protocol for a randomized controlled trial.

BACKGROUND: This document describes a research protocol for a study designed to estimate the impact of implementing a reminder system for medical providers on the use of isoniazid preventative therapy (IPT) for adults living with HIV in western Kenya. People living with HIV have a 5% to 10% annual risk of developing active tuberculosis (TB) once infected with TB bacilli, compared to a 5% lifetime risk in HIV-negative people with latent TB infection. Moreover, people living with HIV have a 20-fold higher risk of dying from TB. A growing body of literature suggests that IPT reduces overall TB incidence and is therefore of considerable benefit to patients and the larger community. However, in 2009, of the estimated 33 million people living with HIV, only 1.7 million (5%) were screened for TB, and about 85,000 (0.2%) were offered IPT. METHODS/DESIGN: This study will examine the use of clinical decision-support reminders to improve rates of initiation of preventative treatment in a TB/HIV co-morbid population living in a TB endemic area. This will be a pragmatic, parallel-group, cluster-randomized superiority trial with a 1:1 allocation to treatment ratio. For the trial, 20 public medical facilities that use clinical summary sheets generated from an electronic medical records system will participate as clusters. All HIV-positive adult patients who complete an initial encounter at a study cluster and at least one return encounter during the study period will be included in the study cohort. The primary endpoint will be IPT prescription at 3 months post the initial encounter. We will conduct both individual-level and cluster-level analyses. Due to the nature of the intervention, the trial will not be blinded. This study will contribute to the growing evidence base for the use of electronic health interventions in low-resource settings to promote high-quality clinical care, health system optimization and positive patient outcomes. Trial registration ClinicalTrials.gov NCT01934309, registered 29 August 2013.

Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors.

OBJECTIVE: To characterize reverse transcriptase (RT) mutations by their association with extent of nucleoside RT inhibitor (NRTI) therapy. To identify mutational clusters in RT sequences from persons receiving multiple NRTI. DESIGN: A total of 1210 RT sequences from persons with known antiretroviral therapy were analyzed: 641 new sequences were performed at Stanford University Hospital; 569 were previously published. METHODS: Chi-square tests and logistic regression were done to identify associations between mutations and NRTI therapy. Correlation studies were done to identify mutational clusters. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. RESULTS: Mutations at 26 positions were significantly associated with NRTI including 17 known resistance mutations (positions 41, 44, 62, 65, 67, 69, 70, 74, 75, 77, 116, 118, 151, 184, 210, 215, 219) and nine previously unreported mutations (positions 20, 39, 43, 203, 208, 218, 221, 223, 228). The nine new mutations correlated linearly with number of NRTI; 777 out of 817 (95%) instances occurred with known drug resistance mutations. Positions 203, 208, 218, 221, 223, and 228 were conserved in untreated persons; positions 20, 39, and 43 were polymorphic. Most NRTI-associated mutations clustered into three groups: (i) 62, 65, 75, 77, 115, 116, 151; (ii) 41, 43, 44, 118, 208, 210, 215, 223; (iii) 67, 69, 70, 218, 219, 228. CONCLUSIONS: Mutations at nine previously unreported positions are associated with NRTI therapy. These mutations are probably accessory because they occur almost exclusively with known drug resistance mutations. Most NRTI mutations group into one of three clusters, although several (e.g., M184V) occur in multiple mutational contexts.

HIV-1 subtype C reverse transcriptase and protease genotypes in Zimbabwean patients failing antiretroviral therapy.

HIV-1 drug resistance mutations have been identified and characterized mostly in subtype B HIV-1 infection. The extent to which antiretroviral drugs select for drug resistance mutations in non-subtype B HIV-1 is not known. We obtained HIV-1 reverse transcriptase (RT) and protease sequences from 21 Zimbabwean patients failing antiretroviral drug therapy. We compared these sequences with 56 published RT and protease subtype C sequences from untreated patients, 990 RT and 1140 protease subtype B sequences from treated patients, and 340 RT and 907 protease subtype B sequences from untreated patients and identified four mutation categories of subtype C HIV-1. Seventeen of the 21 patients (81%) had known drug resistance mutations. Mutations at 15 RT and 11 protease positions were more common in subtype C isolates than in subtype B isolates. HIV-1 subtype C-infected individuals receiving antiretroviral therapy develop many of the known subtype B drug resistance mutations. Comparison of subtype C RT and protease sequences with a large database of subtype B sequences identified subtype C-specific polymorphisms and candidate drug resistance mutations.

Sleep disturbances among HIV-positive adults: the role of pain, stress, and social support.

OBJECTIVE: Investigate the relationships between pain, stress, social support, and sleep disturbance among a diverse sample of HIV-positive adults. METHOD: Participants (N = 146) completed self-report measures on pain, stress, social support, and sleep disturbance. CD4 T-cell count was obtained from medical records. RESULTS: Greater pain and stress were associated with greater sleep disturbance. Greater assistance from friends was associated with greater sleep disturbance, whereas greater understanding from friends regarding participants' HIV-related stress was associated with less sleep disturbance. CONCLUSION: As expected, pain was significantly associated with sleep disturbance. Additionally, psychosocial variables were strongly associated with sleep. The type of support from friends differentiated whether the support was positively or negatively associated with sleep problems. Social support, depending on the type, may not always be helpful for adults living with HIV/AIDS. Future studies need to examine factors that may mediate the relationship between psychosocial constructs and healthy sleep.

Correlates of sexually transmitted disease infection among adults living with HIV.

This study examined the prevalence of sexually transmitted diseases (STDs) as well as the relationships between STDs and coping strategies used to deal with the stress of living with HIV among adults. The sample comprised 179 men and women, 58% were Caucasian, 54% were male, more than half (61%) were diagnosed with AIDS, 43% were heterosexual, and 39% reported an STD post-HIV diagnosis. Logistic regression analysis indicated that individuals reporting longer time elapsed since HIV diagnosis and greater use of emotion-focused coping were more likely to report STDs. There was an interaction effect between time and coping such that the less time that elapsed since HIV diagnosis and the more an individual used emotion-focused coping, the more likely they were to report an STD. Tailoring interventions to address specific stressors associated with length of time living with HIV, may be a particularly effective prevention strategy.

Posttraumatic stress disorder in women attending human immunodeficiency virus outpatient clinics.

This study examined posttraumatic stress disorder (PTSD) in human immunodeficiency virus (HIV)-positive women seeking medical care. Specifically, we examined traumatic life events, psychiatric treatment, social support, and demographic characteristics in relation to level of PTSD symptoms. We recruited and obtained informed consent from 47 ethnically diverse HIV-positive women from two HIV outpatient clinics in a county medical system. Forty-one of these women provided complete data on measures assessing demographics, traumatic life events, PTSD symptoms, social support, and psychotherapy/medical history. Analysis of the data demonstrated that a high percentage (42%) of the HIV-positive women were likely to meet criteria for full current PTSD, and an additional 22% for partial PTSD. Of the women likely with full PTSD, 59% were not receiving any psychiatric treatment, and of those likely with partial PTSD, 78% were not receiving any psychiatric treatment. Also, women reported having experienced a mean of 12 traumatic life events. As hypothesized, the level of PTSD was significantly related to the number of life events experienced (rs = 0.52, p < 0.001), and to perceived social support from friends (rs = - 0.34, p < 0.02) and family (rs = - 0.29, p < 0.05). Given the high percentages of women who were found to have experienced traumatic life events and high levels of PTSD symptoms, it seems important to assess and treat PTSD in women with HIV/acquired immune deficiency syndrome (AIDS).

Social support, substance use, and denial in relationship to antiretroviral treatment adherence among HIV-infected persons.

This study examined the relationship of adherence to antiretroviral treatment with three types of social support (partner, friends, and family) and use of two coping strategies (denial and substance use). Participants were 73 men and women with HIV infection drawn from a larger sample of 186 clinical trial patients. Based on inclusion criteria, parent trial participants taking antiretroviral therapies, and those with complete data on self-reported measures of adherence were considered eligible for the present study. Overall, 26% of participants were found to be nonadherent, which was defined as one or more missed doses of treatment in the prior 4-day period. Logistic regression analysis was conducted to determine associations of sociodemographic and psychosocial variables with adherence to antiretroviral regimen. Results indicated that heterosexual participants (p < 0.01) and participants of Latino ethnicity (p < 0.05) were significantly more likely to report missed medications. Perceived satisfaction with support from a partner was associated with taking antiretroviral therapy as prescribed, whereas satisfaction with support from friends and from family was not significantly related to adherence. Examination of coping strategies showed that participants reporting drug and alcohol use (p <.05) to cope with HIV-related stress were more likely to be nonadherent. These findings call for adherence interventions designed to address barriers and strengths, such as community norms or traditional cultural values, specific to certain populations. Furthermore, couple-based approaches enlisting partner support may help persons living with HIV to adhere to antiretroviral regimens.

Alternative therapies: a common practice among men and women living with HIV.

This study examined the prevalence and factors associated with alternative therapy use in an ethnically diverse, gender-balanced sample of persons living with HIV/AIDS. More than two thirds (67%) of the participants who were taking HIV-related medications were also taking an alternative supplement. Half of the sample (50%) reported that they took one or more multivitamins, 17% reported using mineral supplements, 12% reported using Chinese herbs, and 12% reported using botanicals. Substantial proportions of the sample also reported using acupuncture (31%), massage (23%), and meditation (28%) to specifically treat HIV-related symptoms. Women were four times more likely to use alternative therapies than men. Also, Caucasians were nearly four times more likely to use alternative treatments compared to other ethnic groups. The results of this study indicate a strong need to assess individual patients' use of alternative treatment approaches as well as to further investigate their efficacy among HIV-positive patients.