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Three different patterns of CD4 recovery in a cohort of Chinese HIV patients following antiretroviral therapy - a five-year observational study

Naftalin CM, Wong NS, Chan DP, Wong KH, Reidpath DD, Lee SS

Int J STD AIDS, 2015 Oct;26(11):803-9.
PMID: 25281539 DOI: 10.1177/0956462414553826

To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.

Matched MeSH terms: Antiretroviral Therapy, Highly Active*
Fulltext Lipopolysaccharide, immune activation, and liver abnormalities in HIV/hepatitis B virus (HBV)-coinfected individuals receiving HBV-active combination antiretroviral therapy

Crane M, Avihingsanon A, Rajasuriar R, Velayudham P, Iser D, Solomon A, et al.

J Infect Dis, 2014 Sep 1;210(5):745-51.
PMID: 24585898 DOI: 10.1093/infdis/jiu119

We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods
Factors influencing the quality of life in patients with HIV in Malaysia

Hasanah CI, Zaliha AR, Mahiran M

Qual Life Res, 2011 Feb;20(1):91-100.
PMID: 20737215 DOI: 10.1007/s11136-010-9729-y

PURPOSE: The aim of this study was to determine the socio-demographic, clinical and psychological factors influencing the quality of life (QOL) in patients with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS).
METHODS: This was a cross-sectional study on 271 patients with HIV infection attending an HIV clinic in Kota Bharu, Malaysia. Participants completed the Malay version of the Functional Assessment of HIV Infection (FAHI) and Malay Hospital Anxiety Depression Scale (HADS).
RESULTS: The patients functioned satisfactorily in the physical domain. They were mostly impaired in the social domain. Those who acquired the HIV infection via a heterosexual route seemed to have a significantly lower social well-being, while those who acquired HIV via drug injection were not associated with losses in the overall QOL or any of its domains. Non-disclosure paradoxically had a greater effect on social well-being. About 38% had possible anxiety, depression or both, and these emotional disturbances were significantly associated with total FAHI and its five domains.
CONCLUSIONS: Psychological and social well-beings were more affected than physical well-being in out-patients with HIV infection in Kota Bharu, Malaysia. The study suggests that the patients with HIV infection should receive better psycho-education and psychological intervention.
Study site: Infectious Disease clinic, Hospital Raja Perempuan Zainab II, Kota Bharu Kelantan, Malaysia

Matched MeSH terms: Antiretroviral Therapy, Highly Active
HIV Treatment Adherence - A Shared Burden for Patients, Health-Care Providers, and Other Stakeholders

Abdulrahman SA, Ganasegeran K, Rampal L, Martins OF

AIDS Rev, 2019;21(1):28-39.
PMID: 30899114 DOI: 10.24875/AIDSRev.19000037

Successful HIV treatment is contingent on sustained high levels of treatment adherence. Several barriers to optimal adherence have been documented. In this article, we first review the global burden of non-adherence among HIV/AIDS positive individuals on a public health scale. Second, we synthesized available evidence from different study designs and stratified across the European, African, and Asian literature to determine the factors influencing adherence to scheduled clinic appointments and medication non-adherence. Third, we discuss common measurement techniques that quantify the magnitude of non-adherence, their relative advantages and limitations in current practice. From January to May 2018, we reviewed guidelines, standard operating procedures, journal articles, and book chapters on treatment adherence among HIV patients receiving adherence to antiretroviral therapy (ART) globally. We searched PubMed, Medline, Google Scholar, and Cochrane Database of Systematic Reviews with the search terms "adherence," "adherence behavior," "medication adherence," and "HIV patients," or "HIV/AIDS," and "Antiretroviral Therapy" or "ART" or "ARVs" or "highly active ART " from 2000 to 2017. We also identified articles through searches of authors' files and previous research on HIV. We included only papers published in English in this review. We then generated a final list of reference on the basis of originality and the broad scope of this review. We found rich literature evidence of research findings and best practice recommendations on the importance of adherence in HIV/AIDS management, a general understanding of factors associated with non-adherence and approaches to investigating non-adherence behavior among different populations. We observed significant contextual differences exist with regard to barriers and burden of non-adherence among these populations.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Lymphomatoid papulosis presenting as a rash in a patient with HIV infection

Warren S, Li V, Drayton R, May K

Int J STD AIDS, 2018 11;29(11):1120-1122.
PMID: 29665741 DOI: 10.1177/0956462418767183

A 43-year-old Malaysian man with well-controlled HIV infection on combination antiretroviral therapy presented with a six-week history of a widespread rash. The patient was otherwise well but was developing new lesions on a daily basis. Referral to Dermatology instigated punch biopsies, which revealed a diagnosis of lymphomatoid papulosis type A. This case highlights the importance of swift referral, especially in cases of spontaneous regression of symptoms, in order to obtain the correct diagnosis. In most patients, this condition tends to be chronic, with its chronicity and benign clinical course setting it apart from cutaneous anaplastic T-cell lymphoma and Hodgkin's disease, which are major entities in the histological differential diagnosis.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Fulltext Predictors of linkage to HIV care and viral suppression after release from jails and prisons: a retrospective cohort study

Loeliger KB, Altice FL, Desai MM, Ciarleglio MM, Gallagher C, Meyer JP

Lancet HIV, 2018 02;5(2):e96-e106.
PMID: 29191440 DOI: 10.1016/S2352-3018(17)30209-6

BACKGROUND: Incarceration provides an opportunity for engagement in HIV care but is associated with poor HIV treatment outcomes after release. We aimed to assess post-release linkage to HIV care (LTC) and the effect of transitional case management services.
METHODS: To create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut, USA (2007-14), we linked administrative custody and pharmacy databases with mandatory HIV/AIDS surveillance monitoring and case management data. We examined time to LTC (defined as first viral load measurement after release) and viral suppression at LTC. We used generalised estimating equations to show predictors of LTC within 14 days and 30 days of release.
FINDINGS: Among 3302 incarceration periods for 1350 individuals between 2007 and 2014, 672 (21%) of 3181 periods had LTC within 14 days of release, 1042 (34%) of 3064 had LTC within 30 days of release, and 301 (29%) of 1042 had detectable viral loads at LTC. Factors positively associated with LTC within 14 days of release are intermediate (31-364 days) incarceration duration (adjusted odds ratio 1·52; 95% CI 1·19-1·95), and transitional case management (1·65; 1·36-1·99), receipt of antiretroviral therapy during incarceration (1·39; 1·11-1·74), and two or more medical comorbidities (1·86; 1·48-2·36). Reincarceration (0·70; 0·56-0·88) and conditional release (0·62; 0·50-0·78) were negatively associated with LTC within 14 days. Hispanic ethnicity, bonded release, and psychiatric comorbidity were also associated with LTC within 30 days but reincarceration was not.
INTERPRETATION: LTC after release is suboptimal but improves when inmates' medical, psychiatric, and case management needs are identified and addressed before release. People who are rapidly cycling through jail facilities are particularly vulnerable to missed linkage opportunities. The use of integrated programmes to align justice and health-care goals has great potential to improve long-term HIV treatment outcomes.
FUNDING: US National Institutes of Health.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods
Fulltext Efavirenz does not cause false-positive urine cannabis test in HIV-infected patients on Highly Active Anti-Retroviral Therapy

Koh KC, Lee WY, Eh ZW, Ismail NJ, Tee PS, Othman A, et al.

Med J Malaysia, 2013 Jun;68(3):249-52.
PMID: 23749016

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used in combination with other drugs for the treatment of patients with HIV infection. Efavirenz has been reported to cause a positive urine cannabis test reaction which may create problems between HIV-infected patients on Efavirenz and law enforcement agencies. Doctors are at loss whether to issue documents certifying the potential false positive urine cannabis test with Efavirenz to patients. We investigated if the urine of HIV-infected patients on Efavirenz caused a positive urine cannabis test using the AxSYM Cannabinoids Assay®. Urine samples from 51 eligible patients on Efavirenz were tested for cannabis. All tested negative except for one who had used cannabis the day before. Efavirenz does not cause false positive urine cannabis test with the AxSYM Cannabinoids Assay®. Certification documents from doctors are therefore unnecessary.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Characteristics of HIV-infected tuberculosis patients in Kota Bharu Hospital, Kelantan from 1998 to 2001

Mohammad Z, Naing NN

Southeast Asian J. Trop. Med. Public Health, 2004 Mar;35(1):140-3.
PMID: 15272757

To characterize the demographic profiles, clinical features, radiological patterns and outcomes of treatment of HIV-infected TB patients, a descriptive study was carried out on 149 HIV-infected TB cases diagnosed from 1998 through 2001 at Kota Bharu Hospital, Kelantan, Malaysia. The majority of the patients were males (94.6%), single (45.0%), ethnic Malay (94.0%) with a mean age of 34 years (standard deviation 7.8, range 18-76). The most common HIV transmission category was through injecting drug use (73.8%) and being the inmates or former inhabitants of drug rehabilitation centers and prisons were the commonest high-risk groups. One hundred and seventeen patients were diagnosed as having pulmonary TB, while about 20% were extra-pulmonary in type with 9 cases of milliary TB. The majority (45%) presented with cough symptoms while only 51% had a positive sputum smear. Fifty-five percent were found to have pulmonary lesions on chest x-ray, such as localized, milliary or diffuse pulmonary infiltrates, or opacities. Eight (5.4%) had pleural lesions while another 8 cases had hilar or mediastinal lymph node lesions. Overall, fifty-eight (38.9%) patients had died by the completion of data collection. The median weeks or survival from the time of starting TB treatment was 13.5 (range 1-56) and the majority of them (74%) died without completing the 6-month regime of treatment.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods
Fulltext Toxoplasmosis in HIV/AIDS: a living legacy

Nissapatorn V

Southeast Asian J. Trop. Med. Public Health, 2009 Nov;40(6):1158-78.
PMID: 20578449

Toxoplasmosis has historically been considered one of the most important opportunistic infections detected in HIV/AIDS patients. The prevalence rates of latent Toxoplasma infections in HIV-infected patients has been found to vary greatly from 3% to 97%. Prevalence has been found to be related to ethnicity, certain risk factors, and reactivation of toxoplasmosis. Prior to antiretroviral therapy, toxoplasmic encephalitis (TE) was the most common focal cerebral lesion detected in AIDS patients with Toxoplasma infection, occurring in approximately half of Toxoplasma-seropositive patients. Other forms of dissemination have also been reported in AIDS patients in sites such as the eyes, lungs, heart and spinal cord. Anti-Toxoplasma therapy and chemoprophylaxis have shown effectiveness in reducing the incidence of TE, while noncompliance has been identified as a cause of relapse in these settings. Toxoplasmosis is one of the most common neuropathological complications found at autopsy. Rapid progress in the development of highly active antiretroviral therapy (HAART) has changed the observed patterns with TE, for which there has been a marked decrease in overall incidence. Subsequently, TE has been found to be significantly associated with the so-called "neurological immune restoration inflammatory syndrome" (NIRIS). Toxoplasma screening programs are recommended for all newly diagnosed HIV-positive patients. Chemoprophylaxis should be considered in HIV-infected patients who have a CD4 < 200 cells/mm3, particularly in settings where resources are limited and there is not access to HAART. TE remains a cause of morbidity and mortality among AIDS patients.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Fulltext Evaluation of Selected Outcomes of Combination Antiretroviral Therapy: Yemen Cohort Retrospective Descriptive Studies

Nabih MF, Puteh SEW, Nur AM

Sci Rep, 2019 12 27;9(1):19923.
PMID: 31882645 DOI: 10.1038/s41598-019-56314-0

In 2007, HIV treatment services were established in five main governorates out of twenty-two which resulted in low access to services and poor treatment outcomes. The main goal of this study was to evaluate and analyse the selected treatment outcomes of eight cohorts of PLHIV who were treated with cART during 2007-2014. The method used was a retrospective descriptive study of 1,703 PLHIV who initiated cART at five public health facilities. The results: Retention rate was less than 80%, male: female ratio 1.661, with a mean age of 35 years (±9.2 SD), 85% had been infected with HIV via heterosexual contact. 65% of patients presented with clinical stages 3 and 4, and 52% of them were initiated cART at a CD4 T-cell count ≤200 cells/mm. 61% of cART included Tenofovir and Efavirenz. TB treatment started for 5% of PLHIV, and 22% developed HIV-related clinical manifestations after cART initiation. 67% of PLHIV had experienced cART substitution. The mean AIDS-mortality rate was 15% and the mean LTFU rate was 16%. Conclusion: Although cART showed effectiveness in public health, mobilization of resources and formulation of better health policies are important steps toward improving access to cART and achieving the desired treatment outcomes.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods
Fulltext Mobile phone reminders and peer counseling improve adherence and treatment outcomes of patients on ART in Malaysia: A randomized clinical trial

Abdulrahman SA, Rampal L, Ibrahim F, Radhakrishnan AP, Kadir Shahar H, Othman N

PLoS One, 2017;12(5):e0177698.
PMID: 28520768 DOI: 10.1371/journal.pone.0177698

BACKGROUND: Adherence to treatment remains the cornerstone of long term viral suppression and successful treatment outcomes among patients receiving Antiretroviral Therapy (ART).
OBJECTIVE(S): Evaluate the effectiveness of mobile phone reminders and peer counseling in improving adherence and treatment outcomes among HIV positive patients on ART in Malaysia.
METHODS: A single-blind, parallel group RCT conducted in Hospital Sungai Buloh, Malaysia in which 242 adult Malaysian patients were randomized to intervention or control groups. Intervention consisted of a reminder module delivered through SMS and telephone call reminders by trained research assistants for 24 consecutive weeks (starting from date of ART initiation), in addition to adherence counseling at every clinic visit. The length of intended follow up for each patient was 6 months. Data on adherence behavior of patients was collected using specialized, pre-validated Adult AIDS Clinical Trial Group (AACTG) adherence questionnaires. Data on weight, clinical symptoms, CD4 count and viral load tests were also collected. Data was analyzed using SPSS version 22 and R software. Repeated measures ANOVA, Friedman's ANOVA and Multivariate regression models were used to evaluate efficacy of the intervention.
RESULTS: The response rate after 6 months follow up was 93%. There were no significant differences at baseline in gender, employment status, income distribution and residential location of respondents between the intervention and control group. After 6 months follow up, the mean adherence was significantly higher in the intervention group (95.7; 95% CI: 94.39-96.97) as compared to the control group (87.5; 95% CI: 86.14-88.81). The proportion of respondents who had Good (>95%) adherence was significantly higher in the intervention group (92.2%) compared to the control group (54.6%). A significantly lower frequency in missed appointments (14.0% vs 35.5%) (p = 0.001), lower viral load (p = 0.001), higher rise in CD4 count (p = 0.017), lower incidence of tuberculosis (p = 0.001) and OIs (p = 0.001) at 6 months follow up, was observed among patients in the intervention group.
CONCLUSION: Mobile phone reminders (SMS and telephone call reminders) and peer counseling are effective in improving adherence and treatment outcomes among HIV positive patients on ART in Malaysia. These findings may be of potential benefit for collaborative adherence planning between patients and health care providers at ART commencement.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods*
Osteonecrosis with renal damage in HIV patients undergoing HAART

Chitra P, Bakthavatsalam B, Palvannan T

Biomed Pharmacother, 2014 Sep;68(7):881-5.
PMID: 25194446 DOI: 10.1016/j.biopha.2014.07.017

Rheumatoid arthritis in HIV patients undergoing HAART is associated with increased risk of side effect. Elevation of uric acid (UA) is important in tissue damage, deposition of crystal in joints leads to the development of rheumatoid arthritis in the HAART complaint group. This study was carried out to investigate the relationship of uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group. Moreover; the ratio of uric acid/cystatin C, uric acid/urea and uric acid/creatinine were also studied. To analyze the progression of HIV, the immunological parameters were correlated with uric acid. Our result showed a statistically high significant increase in uric acid, RA factor, ANA, ESR, cystatin C, urea and creatinine in the HAART complaint group when compared to HAART non-complaint group, early stage and control. The ratio of uric acid/cystatin C, uric acid/urea, uric acid/creatinine were significantly increased in the HAART complaint group. Statistically significant positive correlation was observed between uric acid and cystatin C, urea, creatinine, absolute CD4 and CD8 count. The increased level of uric acid, RA factor, ANA, ESR, cystatin C and increased ratio of uric acid/cystatin C in the HAART complaint group might conclude the mechanism underlying the increased risk for rheumatoid arthritis in the HAART complaint group which may relate to the combined effects of low-grade inflammation and renal dysfunction.

Study done in India

Matched MeSH terms: Antiretroviral Therapy, Highly Active/adverse effects*
Beta-2 microglobulin as an immunological marker to assess the progression of human immunodeficiency virus infected patients on highly active antiretroviral therapy

Chitra P, Bakthavatsalam B, Palvannan T

Clin Chim Acta, 2011 May 12;412(11-12):1151-4.
PMID: 21300045 DOI: 10.1016/j.cca.2011.01.037

Acquired immune deficiency syndrome (AIDS) defines the end stage of Human immunodeficiency viral (HIV) infection before the introduction of highly active antiretroviral therapy (HAART). This study was carried out to assess the serum β-2 microglobulin (B2M) as a marker for progression of HIV infected patients undergoing HAART.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Altered phenotype and function of NK cells infiltrating human papillomavirus (HPV)-associated genital warts during HIV infection

Bere A, Tayib S, Kriek JM, Masson L, Jaumdally SZ, Barnabas SL, et al.

Clin Immunol, 2014 Feb;150(2):210-9.
PMID: 24440646 DOI: 10.1016/j.clim.2013.12.005

HIV-infected individuals experience more persistent HPV infections and are less likely to resolve genital warts. This study compared phenotype and functions of NK and T cells from genital warts and blood from 67 women. We compared in vitro functional responses of NK and T cells by multiparametric flow cytometry. HIV+ women had significantly lower frequencies of CD4 T cells in warts (p = 0.001) and blood (p = 0.001). While the distribution of NK cell subsets was similar, HIV+ women tended to have lower frequencies of CD56(Dim) NK cells in both blood (p = 0.0001) and warts (p = 0.006) than HIV- women. Wart NK cells from HIV+ women expressed significantly lower CD107a and produced IFN-γ. HAART status was not associated with differences in NK cell functionality. We conclude that wart NK cells from HIV+ women have defects in their ability to degranulate and/or secrete IFN-γ, which may provide insights into why HIV+ women fail to spontaneously resolve genital warts.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Enhanced Solubility and Bioavailability of Dolutegravir by Solid Dispersion Method: In Vitro and In Vivo Evaluation-a Potential Approach for HIV Therapy

Chaudhary S, Nair AB, Shah J, Gorain B, Jacob S, Shah H, et al.

AAPS PharmSciTech, 2021 Apr 09;22(3):127.
PMID: 33835317 DOI: 10.1208/s12249-021-01995-y

Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased Cmax (14.56 μg/mL) when compared to the physical mixture (4.12 μg/mL) and pure drug (3.45 μg/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99±10.07 μg/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45±6.58 μg/h/mL) and pure drug (49.27±6.16 μg/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods*
How well does self-reported adherence fare compared to therapeutic drug monitoring in HAART?

Bulgiba A, Mohammed UY, Chik Z, Lee C, Peramalah D

Prev Med, 2013;57 Suppl:S34-6.
PMID: 23313585 DOI: 10.1016/j.ypmed.2013.01.002

The aim of the study was to determine how well self-reported adherence fares compared to therapeutic drug monitoring in monitoring HAART adherence.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods*; Antiretroviral Therapy, Highly Active/psychology
Disseminated histoplasmosis mimicking an acute appendicitis

Marsilla MM, Khairunisa AA, Azyani Y, Petrick P

Malays J Pathol, 2019 Aug;41(2):223-227.
PMID: 31427560

INTRODUCTION: Histoplasmosis can present in a myriad of clinical manifestations, which often makes its diagnosis difficult and occasionally, deceptive.
CASE REPORT: We describe a case of a 33 years old gentleman who was clinically diagnosed as acute appendicitis at initial presentation in view of a one-week history of fever, right lower quadrant abdominal pain- and guarding at right iliac fossa. He had thrombocytopenia and lymphopenia on presentation. Mesenteric lymphadenitis and small bowel lesion were found intraoperatively, which was respectively biopsied and resected. Histopathological result confirms disseminated histoplasmosis. Retroviral screen was positive. He was treated with amphotericin B for one week, subsequently switched to oral itraconazole, followed by initiation of highly active antiretroviral therapy (HAART).
DISCUSSION: This case illustrates the various nature of histoplasmosis presentation. A high index of suspicion is needed to clinch the diagnosis and subsequently institute prompt treatment as disseminated disease can be fatal if left untreated in an immunosuppressed host.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
A report from the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (June 30-July 3, 2013 - Kuala Lumpur, Malaysia)

Rabasseda X

Drugs Today, 2013 Aug;49(8):509-17.
PMID: 23977668 DOI: 10.1358/dot.2013.49.8.2033100

Effective antiretroviral drugs have been developed that, if continuously administered (although with simplification strategies once a patient's viral titer is suppressed) allow for a functional cure resulting in an almost normal life despite the presence of viral reservoirs. In that sense, observations that combination antiretroviral therapy has an untoward suppressive effect on antibody-dependent cellular cytotoxicity against T cells permitting the establishment of such viral reservoirs were discussed for its implications in the use of vaccines and/or modulators of the immune function to clear latent infections and the risk for reactivation (Madhavi, V. et al., Abst MOLBPE05). In addition to latent viral reservoirs, individual patient characteristics may also influence response to antiretroviral therapy, as exemplified by the increased likelihood of highly active antiretroviral therapy in patients carrying certain polymorphic variants (rs2229109, rs6961419) of the P-glycoprotein 1 gene (Dias, J. et al., Abst MOPE034). These, and many other important news derived from research into novel approaches to fight HIV infection were discussed during the International AIDS Society (IAS) meeting in Kuala Lumpur, as summarized in the following report.

Matched MeSH terms: Antiretroviral Therapy, Highly Active/methods*
Fulltext Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals

Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al.

Sci Rep, 2018 09 24;8(1):14277.
PMID: 30250162 DOI: 10.1038/s41598-018-32585-x

We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.

Matched MeSH terms: Antiretroviral Therapy, Highly Active
Fulltext HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution

Yap SH, Abdullah NK, McStea M, Takayama K, Chong ML, Crisci E, et al.

PLoS One, 2017;12(10):e0186000.
PMID: 29016635 DOI: 10.1371/journal.pone.0186000

BACKGROUND: Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants.
METHOD: In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression.
RESULTS: A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation.
CONCLUSION: Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

Matched MeSH terms: Antiretroviral Therapy, Highly Active

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