Majority Of Human Immunodeficiency Virus Research Articles

Infectious etiologies among post-donation deferrals in a military blood donation center.

The burden of transfusion-transmitted infections among blood recipients remains low due to extensive pre- and post-donation screening. However, the military has the unique challenge of providing blood in austere environments with limited testing capabilities. This study evaluates the infectious etiologies of deferred blood donors at a large military blood donation center. All blood donors at the Armed Service Blood Bank Center, San Antonio, between 2017 and 2022 with positive post-donation screening for hepatitis C (HCV), hepatitis B (HBV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV-I/II), Zika (2018-2021), West Nile virus, Trypanosoma cruzi, Treponema pallidum, or Babesia microti (2020-2022) were evaluated. Donors were deferred based on Food and Drug Administration (FDA) guidance. Two-hundred and thirteen (213) donors met FDA criteria for deferral. T. pallidum (n = 45, 50.3 per 100,000), HCV (n = 34, 38.0 per 100,000), and HBV (n = 19, 21.2 per 100,000) were the most common pathogens among those with both positive screening and confirmatory testing. The majority of HIV (95%), Chagas (78%), HTLV-I/II (50%) deferrals were due to indeterminate confirmatory tests following initial positive screens. The majority of deferrals for HBV were for a second occurrence of a positive screen despite negative confirmatory testing. The rates of post-donation deferral for transfusion-transmissible infections were low in this military cohort. Our findings suggest that donor testing in deployed service members should focus on HBV, HCV, and T. pallidum and highlight the need for better diagnostics for HIV, Chagas, and HTLV-I/II.

Missed Opportunities for Prevention: Prevalence and Incidence of HIV and HCV Diagnoses Among a Cohort of Individuals Discharged from an Urban Hospital with Injection Drug Related Diagnoses, 2012-2019.

Risk for HIV and hepatitis C virus (HCV) infections have increased due to the on-going opioid epidemic and unsafe injection practices. We estimated prevalence and incidence of HIV and HCV diagnoses among people who inject drugs (PWID) from hospital-based clinical encounters. We linked clinical encounters at an Atlanta hospital during 2012-2018 with state HIV and HCV surveillance records to examine prevalence of infections at discharge and incidence of infections post-clinical encounter. At discharge, 32.9% and 28.6% of patients with IDU-related clinical encounters had an HIV or HCV diagnosis, respectively. HIV and HCV diagnoses at time of discharge were mostly among 40-64 year-old patients, males, and Black/African Americans. Post-clinical encounter, 3.8% of patients were later diagnosed with HIV, and 16.5% were later diagnosed with HCV, translating to incidence rates of 9.3 per 1,000 person-years and 41.5 per 1,000 person-years, respectively. The majority of HIV and HCV diagnoses post-clinical encounter occurred among Black/African Americans and males. Of patients with HIV and HCV diagnoses post-clinical encounter, 27.3% and 11.9% had been tested during their clinical encounter, respectively. Targeted interventions for HIV/HCV prevention, screening, diagnosis and linkage to treatment are needed to reduce incidence of new infections among PWID.

Deciphering the Role of Mucosal Immune Responses and the Cervicovaginal Microbiome in Resistance to HIV Infection in HIV-Exposed Seronegative (HESN) Women.

ABSTRACTThe female genital tract (FGT) is an important site of human immunodeficiency virus (HIV) infection. Discerning the nature of HIV-specific local immune responses is crucial for identifying correlates of protection in HIV-exposed seronegative (HESN) individuals. The present study involved a comprehensive analysis of soluble immune mediators, secretory immunoglobulins (sIg), natural killer (NK) cells, CXCR5+ CD8+ T cells, T follicular helper (Tfh) cells, and T regulatory cells (Tregs) in the vaginal mucosa as well as the nature and composition of the cervicovaginal microbiome in HESN women. We found significantly elevated antiviral cytokines, soluble immunoglobulins, and increased frequencies of activated NK cells, CXCR5+ CD8+ T cells, and Tfh cells in HESN females compared to HIV-unexposed healthy (UH) women. Analysis of the genital microbiome of HESN women revealed a greater bacterial diversity and increased abundance of Gardnerella spp. in the mucosa. The findings suggest that the female genital tract of HESN females represents a microenvironment equipped with innate immune factors, antiviral mediators, and critical T cell subsets that protect against HIV infection.IMPORTANCE The vast majority of human immunodeficiency virus (HIV) infections across the world occur via the sexual route. The genital tract mucosa is thus the primary site of HIV replication, and discerning the nature of HIV-specific immune responses in this compartment is crucial. The role of the innate immune system at the mucosal level in exposed seronegative individuals and other HIV controllers remains largely unexplored. This understanding can provide valuable insights to improve vaccine design. We investigated mucosal T follicular helper (Tfh) cells, CXCR5+ CD8+ T cells, natural killer (NK) cells subsets, soluble immune markers, and microbiome diversity in HIV-exposed seronegative (HESN) women. We found a significantly higher level of mucosal CXCR5+ CD8+ T cells, CD4+ Tfh cells, activated NK cell subsets, and antiviral immune cell mediators in HESN women. We also found a higher abundance of Gardnerella spp., microbiome dysbiosis, and decreased levels of inflammatory markers to be associated with reduced susceptibility to HIV infection. Our findings indicate that increased distribution of mucosal NK cells, CXCR5+ CD8+ T cells, Tfh cells, and soluble markers in HIV controllers with a highly diverse cervicovaginal microbiome could contribute effectively to protection against HIV infection. Overall, our findings imply that future vaccine design should emphasize inducing these highly functional cell types at the mucosal sites.

Predictors of Anemia Among HIV-Infected Children on Antiretroviral Therapy in Wolaita Zone, South Ethiopia: A Facility-Based Cross-Sectional Study.

PurposeAnemia is a global public health problem, and the majority of human immunodeficiency virus (HIV)-positive people become anemic at some point in the course of the disease. We lack adequate evidence on the magnitude of anemia among children on highly active antiretroviral therapy in Ethiopia and particularly in South Ethiopia. Thus, this study aimed at determining the proportion and associated factors of anemia among children on highly active antiretroviral therapy in Wolaita zone, South Ethiopia.Patients and MethodsA facility-based cross-sectional study was conducted from November to December 2018 on 256 children from 6 months to 14 years of age who were on antiretroviral therapy. Data were collected through an interview with caregivers and review of medical records. CD4+ cell count was analyzed using FACS Calibur, and hemoglobin level was measured with a Hem cue 301 analyzer. Stool samples were examined for the presence of intestinal parasites by direct wet mount technique. Data analyzed with Stata version 14.0 were conveyed in mean and standard deviation of the mean, median and inter-quartile range. Multivariate analysis was carried out to identify independent predictors of the outcome variable. Adjusted odds ratio with 95% confidence interval was reported.ResultsThe proportion of anemia was found to be 38.8%. Co-trimoxazole prophylaxis (AOR=0.45; 95% CI: 0.21, 0.95), caregivers not receiving nutritional counseling (AOR=0.90; 95% CI: 0.01, 0.98) and presence of intestinal parasites (AOR=3.10; 95% CI: 1.39, 6.88) were associated with anemia.ConclusionThe proportion of anemia found in this study is a moderate public health problem. Health education programs in antiretroviral therapy clinics should be targeted at appropriate dietary practice, and appropriate hand washing and other hygienic practices to prevent intestinal parasitic infections. Co-trimoxazole prophylaxis should be given to all eligible children based on the recommendation.

HIV infection and Mycoplasma co-infection: case-control study in a female population of Douala (Cameroon)

Objective: To determine the impact of Human Immuno-Deficiency Virus (HIV) on co-infection with Mycoplasma hominis and Ureaplasma urealyticum in HIV-infected women. Methodology: A case-control analytical study based on standardized questionnaire interview and cervical sample collection after informed consent obtained among HIV-positive and HIV-negative women from January 2nd, 2017 to June 30th, 2017 received at the laboratory of Laquintinie Hospital in Douala. Samples collected were used for mycoplasma research, quantification, and antibiogram using the mycoplasma IES kits. Socio-demographic, clinical and biological variables of interest were entered and analyzed on Microsoft Office Excel 2013 and Statistical Package for Social Sciences (SSPS) software version 20 and the chi-square correlation test was used with significance at the threshold of P <5%. Results: We analysed 136 samples of women aged 18-65years, among which 96 HIV+(cases) matched with 40 HIV-(controls). The mean age of the case group was 39.08±10.22 years and that of the control group was 33.28±8.68 years. Genital mycoplasmas were found in 58.3% of cases, with a high frequency for U. urealyticum (19.8%) against 2.1% for M. hominis and the two germs were associated in 32.3% of cases. In the control group, the carrier rate was 62.5%, with a frequency of 17.5% for Ureaplasma alone and no carrier for M. hominis alone. Co-infection with the two germs in this group was 40%. The majority of HIV+women had a CD4 count above 200, and no significant association was found between CD4 count and the presence of mycoplasma in these women (P=0.094). Conclusion: Mycoplasma infection is common in HIV+ women. However, there is no significant association between the CD4 count and the presence of these mycoplasmas.

Oral Coadministration of an Intramuscular DNA/Modified Vaccinia Ankara Vaccine for Simian Immunodeficiency Virus Is Associated with Better Control of Infection in Orally Exposed Infant Macaques.

The majority of human immunodeficiency virus (HIV) type 1 infections in infants are acquired orally through breastfeeding. Toward development of a pediatric HIV vaccine to prevent breastmilk transmission, we tested the efficacy of a simultaneous oral and intramuscular (IM) vaccination regimen for preventing oral simian immunodeficiency virus (SIV) transmission in infant rhesus macaques. Two groups of neonatal macaques were immunized with DNA encoding SIV virus-like particles (DNA-SIV) on weeks 0 and 3, then boosted with modified vaccinia Ankara (MVA) virus expressing SIV antigens (MVA-SIV) on weeks 6 and 9. One group was prime/boosted by the IM route only. Another group was immunized with DNA by both the IM and topical oral (O) buccal routes, and boosted with MVA-SIV by both the IM and sublingual (SL) routes. A third group of control animals received saline by O + IM routes on weeks 0 and 3, and empty MVA by SL + IM routes on weeks 6 and 9. On week 12, infants were orally challenged once weekly with SIVmac251 until infected. The vaccine regimen that included oral routes resulted in reduced peak viremia. The rate of infection acquisition in vaccinated infants was found to be associated with prechallenge intestinal immunoglobulin G (IgG) responses to SIV gp120 and V1V2. Peak viremia was inversely correlated with postinfection intestinal IgG responses to gp120, gp41, and V1V2. These results suggest that codelivery of a pediatric HIV vaccine by an oral route may be superior to IM-only regimens for generating mucosal antibodies and preventing HIV breastmilk transmission in neonates.

SOCIO-DEMOGRAPHIC AND CLINICAL PROFILE OF HIV POSITIVE PATIENTS ATTENDING INTEGRATED COUNSELING & TESTING CENTRE OF A PRIMARY HEALTH CENTRE IN DELHI

Introduction: The Human Immunodeficiency Virus (HIV) infection is a global pandemic affecting principally the sexually active and economically productive population of any country. Additionally the dual epidemic of HIV and TB infection is of growing concern in Asia, where nearly two-third of TB-infected individuals live and where tuberculosis now accounts for 40 percent of HIV/AIDS deaths. Keeping this in mind, a study was conducted to understand the profile of HIV/AIDS patients attending Integrated Counseling and Testing Center (ICTC) located at Primary Health Centre, Palam in Delhi.Methodology: This was a descriptive record based study undertaken at ICTC, PHC PALAM, New Delhi. Records of all HIV seropositive patients identified in reference period (January 2010 to December 2014) were analyzed retrospectively to assess the socio-demographic and clinical profile including possible route of transmission, CD4 counts at the time of first reporting to the Anti Retroviral Treatment (ART) centre and the presence of co-infections including tuberculosis were recorded. Total 77 HIV seropositive patients were identified.Results: Mean Age of presentation of male was 31.18 ± 8.85 years (12-60 years) and female 30.30 ± 10.07 years (7-53 years). Majority of HIV+ persons were married (16% of males and 6% females were unmarried).24% of women were widows. Majority of HIV+ males and females had only primary schooling. 11% males and 21% females were illiterate. Main occupations of HIV+ males were daily wages labor and salaried service or other unspecified four out of 5 HIV+ women were housewives 70% of subjects were either referred from RNTCP or were self reporting. Heterosexual route was the most common route of transmission. Mean CD4 counts Males: 190.48 ± 180.52, Females: 286.21 ± 220.25 (t=2.09; p=0.039, significant).At the time of first reporting to ART centers, mean CD4 count was significantly higher in HIV+ females as compared to males. More than 50% of HIV+ males and 30% of females had co-infection of HIV & TB. CD4 count was associated with gender and co-infection with TB. Significantly higher odds of HIV-TB co-infection among male as compared to females (chi-square=4.49, p=0.034) and odds Ratio=2.76(1.07 – 7.14)Conclusions: Low literacy and some occupations carry higher risk of HIV. CD4 count was associated with gender and co-infection with TB. Odds of co-infection with TB were higher in males. Analysis of information at ICTC & ART centre should be used to monitor and plan HIV prevention and control in the area.SAARC J TUBER LUNG DIS HIV/AIDS, 2017; XIV(1), page: 22-26

Context and social perceptions of blood donation in donors found positive for human immunodeficiency virus in France.

In France, information collected during postdonation interviews showed that a majority of human immunodeficiency virus (HIV)-infected donors were not eligible to donate as per donor selection criteria. In the interest of blood safety, this study aimed to explore the mechanisms of noncompliance with blood donor selection criteria, notably the permanent deferral of men who have sex with men (MSM). Semistructured individual interviews were conducted with 32 blood donors found positive for HIV between mid-2011 and 2014. Topics such as the experience and motivations for donating blood, understanding of selection criteria, sexual risk management, and opinions on donor selection were discussed. Transcripts were analyzed inductively. More than 50% of study participants were noncompliant with donor selection criteria. Reasons for nondisclosure of risk factors in the predonation questionnaire or the predonation interview included stigma, test-seeking motivations, symbolic attachment to blood donation, and context of donation. Compliance to donor criteria was seen as secondary by donors who reaped personal benefits from the symbolism of their donation. Donors lacked self-reflexivity in their assessment of risky sexual behavior. The "window period" and the underlying epidemiologic arguments for donor selection criteria were poorly understood. Nearly all participants disapproved of the permanent ban on blood donations from MSM. This study demonstrated the need for more communication on the epidemiologic basis for donor selection criteria and on the window period to facilitate donor compliance. These findings have already advanced improvements to predonation documents, in a larger context of 2016 donor selection criteria revision.

English

INTRODUCTION: Globally the majority of human immunodeficiency virus (HIV) epidemic is through heterosexual transmission; The complex interaction between STD and the HIV has been demonstrated in many epidemiological, in vitro and clinical studies over the last number of years. Classic STD could facilitate HIV 1 transmission by increasing either the infectiousness of the index case, the susceptibility of the partner, or both.

Human leucocyte antigen-Bw4 and Gag-specific T cell responses are associated with slow disease progression in HIV-1B-infected anti-retroviral therapy-naive Chinese

In China, the majority of human immunodeficiency virus (HIV) infections are predominately subtype B. It is important to characterize the HIV-1 subtype B-specific and its T cell response within the Chinese population, with the aim of identifying protective correlates of immunity to control HIV-1 infections. In this study, we performed a comprehensive analysis looking into the magnitude/strength of T cell responses directed at the Gag protein of the HIV-1 subtype B, one of the most conserved HIV-1 proteins. The study group consisted of anti-retroviral native and chronic HIV-1 subtype B-infected individuals. We used enzyme-linked immunospot (ELISPOT) assay to quantify the total T cell responses to HIV-1 Gag at the single peptide level. Twenty-eight (38%) peptides were recognized in 24 (82·8%) individuals. The p24 was identified as the most frequently recognized subunit protein with the greatest T cell response in the test, which correlated positively with CD4(+) T cell count and inversely with viral load (VL). At the level of the human leucocyte antigen (HLA) supertypes, we detected the highest levels and a significant correlation with both the CD4(+) T cell count and the VL with Gag T cell responses in Bw4/Bw4. These findings demonstrate that (i) the HIV-1B Gag p24-specific immune responses play an important role in controlling viral replication and slowing clinical progression; and (ii) HLA-Bw4/Bw4 allele has stronger T cell responses, which is associated with slow clinical progression in Chinese HIV patients.

Virologic and immunologic outcome of HAART in Human Immunodeficiency Virus (HIV)-1 infected patients with and without tuberculosis (TB) and latent TB infection (LTBI) in Addis Ababa, Ethiopia

BackgroundHIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB.MethodsA total of 232 adults, including 59 HIV patients with clinical TB (HIV + TB+), 125 HIV patients without clinical TB (HIV + TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV + patients (28 TB + and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-γ responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation.ResultsThe majority of HIV + TB- (70%, 81%, 84%) as well as HIV + TB + patients (60%, 77%, 80%) had virologic success (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4+ T-cell counts at 2 years in HIV + TB + (from 110.3 to 289.9 cells/μl), HIV + TB- patients (197.8 to 332.3 cells/μl), HIV + TST- (199 to 347 cells/μl) and HIV + TST + individuals (195 to 319 cells/μl). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-γ response at baseline was significantly lower in HIV + TB + (3.6 pg/ml) compared to HIV-TB + patients (34.4 pg/ml) and HIV + TST + (46.3 pg/ml) individuals; and in HIV-TB + patients compared to HIV-TST + individuals (491.2 pg/ml). By M18 on HAART, the IFN-γ response remained impaired in HIV + TB + patients (18.1 pg/ml) while it normalized in HIV + TST + individuals (from 46.3 to 414.2 pg/ml).ConclusionsOur data show that clinical and latent TB infections do not influence virologic and immunologic outcomes of ART in HIV patients. Despite this, HAART was unable to restore optimal TB responsiveness as measured by Mtb specific IFN-γ response in HIV/TB patients. Improvement of Mtb-specific immune restoration should be the focus of future therapeutic strategies.

THE MOLECULAR BASIS OF RESISTANCE ANTIRETROVIRAL MARKERS AND POLYMORPHISMS OF THE HUMAN IMMUNODEFICIENCY VIRUS-1 SUBTYPE CRF01-AE PROTEASE GENE IN NAÏVE AND TREATMENT FAILURE PATIENTS IN BALI

Application of antiretrovirals (ARVs) in patients with Human Immunodeficiency Virus (HIV) infection has proven to reduce mortality rates and prolong life expectancy. On the other hand, the use of antiretroviral drugs has incited the emergence of HIVDR. The resistance is due to mutation at genes associated with drug resistance. Nowadays, the determination of resistance markers mutations are based on HIV-1 subtype B. However, the majority of HIV in Indonesia, particularly in Bali are of subtype CRF01_AE. Genetic variation between HIV viruses has led to variations in subtypes; therefore, resistance markers of subtype B could be polymorphisms of non-B subtypes. This study aims to determine the number and types of the resistance markers mutations and polymorphisms that occur on the PR gene of HIV-1 subtype CRF01_AE of naïve and treatment failure patients in Bali. This is an observational cross-sectional analytical study, conducted at two VCT clinics in Denpasar, during the period of April 2010 until October 2011. Samples consist of 18 HIV patients with treatment failure and 30 naïve HIV patients. Mutations were evaluated using PCR, sequenced and aligned were carried out using MEGA4. Interpretations of the mutations were made based on the Stanford HIV database. Hypothesis tests used were Mann-Whitney because of abnormal distribution of data. Hypothesis was accepted if the significant level p&lt;0.05. This study found that of the demographic data, only the predisposing factors of the two groups were significantly different (p&lt;0.05). Two patients with treatment failure and 5 naïve patients were found to have L10LV/I mutations. Only one patient with treatment failure had the I54FI mutation. No major mutations were found among the two study groups. The number and types of minor mutations were not significantly different (p&gt;0.05) between the naïve group and treatment failure group. M36I and H69K polymorphisms of the PR gene were found in all the study samples. In conclusion of this study, two types of major mutations were found, L10LV/I and I54FI. The number and types of the resistance markers mutations towards the protease inhibitor (PI) group were not significantly different between the two study groups. M36I, H69K mutations of the PR gene are markers of polymorphisms of HIV-1 subtype CRF01_AE.

Sexual Risk History and Condom Use among People Living with HIV/AIDS in Ogun State, Nigeria

The majority of human immunodeficiency virus (HIV) infections are acquired through unprotected sex between partners; only male or female condoms can reduce the chances of infection with HIV during a sexual act. This study was therefore designed to describe sexual risk history and identify factors associated with condom use among people living with HIV/acquired immunodeficiency syndrome (AIDS) (PLWHAs) in Ogun State, Nigeria. Main outcome measures are sexual and HIV risk history, safe sex practices, and condom use. This study is an analytical cross-sectional study. A total sample of all people living with HIV/AIDS attending secondary health facilities in Ogun State were recruited into the study. A total of 637 were interviewed; median age at first sexual intercourse among the study participants was 19 years (mean age = 18.95, standard deviation [SD] = 4.148) with a median of two lifetime sexual partners (mean = 3.22, SD = 3.57). Majority (71.4%) of the respondents had not been diagnosed with a sexually transmitted infection other than HIV. Precisely 47.7% of men and 52.3% of women had two or more sexual partners in the last 6 months. Men were statistically significantly more likely to have multiple sexual partners when compared with women (P = 0.00). Significantly more women (69.8%) than men (30%) had sexual partners whose HIV status they did not know (P = 0.006). Predictors of condom use were individuals who had multiple sexual partners (odds ratio [OR] = 1.41, confidence interval [CI] = 1.05-1.83) and married (OR = 3.13, CI = 1.15-8.51) with higher level of education (OR = 2.78, CI = 1.39-5.79), with knowledge of partner's serostatus (OR = 2.53, CI = 1.50-4.28), and awareness of reinfection (OR = 1.90, CI = 1.22-2.95). The study indicates that the establishment of effective safe sex practices and condom use behavior among PLWHAs in low-income countries such as the study population requires adequate health education on the transmission of HIV/AIDS and the understanding of the dynamics of family life and gender issues.

Acute coronary syndrome in HIV patients: from pathophysiology to clinical practice.

A majority of human immunodeficiency virus (HIV) infected subjects in developed countries have access to highly active anti-retroviral therapy (HAART), which is associated with significantly improved long term survival. In this setting, clinical attention needs to be focused on the impact of premature atherosclerotic cardiovascular disease (CVD), which already represents a leading cause of morbidity and mortality in these patients. While the higher prevalence of traditional risk factors remains the main culprit of increased CVD risk, HIV infection itself and antiretroviral toxicity are confounding proatherogenic factors. It is therefore critical to treat modifiable risk factors, keeping close attention to drug interactions in these patients with high cardiovascular risk profile.

P07-07. Non-progressive paediatric HIV infection is associated with virus attenuation and increase in CD8+ specific T cell responses over time

Background The majority of Human Immunodeficiency Virus (HIV)infected infants in the developing world progress to AIDS or death within the first year of life. Although a small minority become slow-progressors, the determinants of slow-progression remain to be elucidated. In this context the interactions between the characteristics of the maternal virus transmitted and the infants' adaptive immune responses are likely to be important. We undertook this study to elucidate the contribution of viral and host factors to HIV progression in perinatally-infected infants.

Modifications of residual viraemia in human immunodeficiency virus-1-infected subjects undergoing repeated highly active antiretroviral therapy interruptions

Residual viraemia is detectable in the majority of human immunodeficiency virus (HIV)-infected subjects with plasma HIV-1 RNA <50 copies ml(-1). In the present study, the impact of repeated treatment interruptions on residual HIV-1 viraemia was investigated in 58 subjects enrolled in the ISS-PART, a multicentre, randomized clinical trial comparing 24 months of continuous (arm A) and intermittent (arm B) highly active antiretroviral therapy (HAART). Residual viraemia was measured by a modified Roche Amplicor HIV-1 RNA assay (limit of detection 2.5 copies ml(-1)). At baseline, the median value of residual viraemia was 2.5 copies ml(-1) in both arms; after 24 months, the median value was 2.5 in arm A and 8.3 in arm B. The median change from baseline to month 24 was significantly different between patients under continuous or intermittent HAART: 0 copies ml(-1) (range -125.2 to +82.7) of HIV-1 RNA in arm A versus 2.1 copies ml(-1) (range -80 to +46.8) in arm B (P=0.024). These results suggest that intermittent HAART tends to modify HIV-1 viraemia set point even if a virological response is achieved after HAART reinstitution.

Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope

Worldwide, the majority of human immunodeficiency virus (HIV) infections occur by heterosexual transmission. Thus, the development of a vaccine that can prevent intravaginal HIV infection is an important goal of AIDS vaccine research. To determine which single or combination of systemic and mucosal routes of immunizations of female rhesus macaques with an HIV-1 SF162 envelope protein vaccine induced protection against intravaginal challenge with SHIV. Female rhesus macaques were immunized with an HIV-1 SF162 envelope protein vaccine administered systemically (intramuscularly), or mucosally (intranasally), or as a sequential combination of both routes. The macaques were then challenged intravaginally with SHIV SF162P4, expressing an envelope that is closely matched (homologous) to the vaccine. Macaques receiving intramuscular immunizations, alone or in combination with intranasal immunizations, were protected from infection, with no detectable plasma viral RNA, provirus, or seroconversion to nonvaccine viral proteins, and better preservation of intestinal CD4+ T cells. Serum neutralizing antibodies against the challenge virus appeared to correlate with protection. The results of this study demonstrate that, in the nonhuman primate model, it is possible for vaccine-elicited immune responses to prevent infection after intravaginal administration of virus.

Human Immunodeficiency Virus Viral Load in Blood Plasma and Semen: Review and Implications of Empirical Findings

The majority of human immunodeficiency virus (HIV) infections in the world are sexually transmitted and quantities of HIV in genital fluids are an important transmission risk-determining factor. Estimating men's sexual HIV infectiousness from blood viral load hinges on the association between HIV in blood plasma (BPVL) and semen viral load (SVL). This article reviews research on the association between BPVL and SVL as reported in 19 empirical studies (N = 1226). Findings yielded a mean correlation between BPVL and SVL of 0.45 (SD = 0.20, median = 0.45, range = 0.07-.64). SVL was generally lower than BPVL, but this pattern was variable across studies. Co-occurring sexually transmitted infections (urethritis), nonsuppressive HIV treatments, and drug resistance account for the variability in observed correlations. HIV disease progression does not reliably influence the association between BPVL and SVL. Research is needed to determine the degree to which BPVL as well as SVL predict HIV transmission.

Decreased CXCR3+CD8 T Cells in Advanced Human Immunodeficiency Virus Infection Suggest that a Homing Defect Contributes to Cytotoxic T-Lymphocyte Dysfunction

To exert their cytotoxic function, cytotoxic T-lymphocytes (CTL) must be recruited into infected lymphoid tissue where the majority of human immunodeficiency virus (HIV) replication occurs. Normally, effector T cells exit lymph nodes (LNs) and home to peripheral sites of infection. How HIV-specific CTL migrate into lymphoid tissue from which they are normally excluded is unknown. We investigated which chemokines and receptors mediate this reverse homing and whether impairment of this homing could contribute to CTL dysfunction as HIV infection progresses. Analysis of CTL chemokine receptor expression in the blood and LNs of untreated HIV-infected individuals with stable, chronic infection or advanced disease demonstrated that LNs were enriched for CXCR3(+) CD8 T cells in all subjects, suggesting a key role for this receptor in CTL homing to infected lymphoid tissue. Compared to subjects with chronic infection, however, subjects with advanced disease had fewer CXCR3(+) CD8 T cells in blood and LNs. CXCR3 expression on bulk and HIV-specific CD8 T cells correlated positively with CD4 count and negatively with viral load. In advanced infection, there was an accumulation of HIV-specific CD8 T cells at the effector memory stage; however, decreased numbers of CXCR3(+) CD8 T cells were seen across all maturation subsets. Plasma CXCL9 and CXCL10 were elevated in both infected groups in comparison to the levels in uninfected controls, whereas lower mRNA levels of CXCR3 ligands and CD8 in LNs were seen in advanced infection. These data suggest that both CXCR3(+) CD8 T cells and LN CXCR3 ligands decrease as HIV infection progresses, resulting in reduced homing of CTL into LNs and contributing to immune dysfunction.

Reconstructing occupation after HIV infection: Lessons from women's experiences

For the majority of human immunodeficiency virus (HIV) positive women in the United States, social and economic circumstances limit options for meaningful occupation and access to relevant healthrelated services. Quality of life is highly contingent upon the extent to which individuals can fulfil their life plans. This triangulated study explored relationships among HIV and acquired immunodeficiency syndrome (AIDS) status, engagement in meaningful occupations, services associated with AIDS-related health care and self-reported quality of life for HIV positive women. Survey data from the Multidimensional Quality of Life Questionnaire for People with HIV was collected, along with numeric health indicators and narrative from two semi-structured interviews addressing occupation and health. In total, 15 women representing three cohorts along the illness trajectory of HIV and AIDS were recruited from an urban health-care facility designed to provide AIDS-related services. Most of the women in the study relayed a protracted process of learning to live with HIV and several of the women viewed HIV infection as an event that led to enhanced quality of life. The need for comprehensive health and support services was evident in every case, regardless of health status.