Journal of AIDS & Clinical Research

With more than 35 million infected in over thirty years, the HIV pandemic has been a unique challenge to the scientific community. The development of effective anti-retroviral therapy has decreased morbidity and mortality of those infected with HIV, but a comprehensive approach that includes effective prevention strategies will be needed to curb this unique pandemic. Vaccines remain the best option, but the development of a safe and effective preventive HIV vaccine has defied decades of research. Over 30 products have been tested in more than 85 trials, but no safe and effective vaccine has been developed yet. Despite these setbacks, these decades of research have broadened the understanding of HIV immunopathogenesis and closer to the goal of a successful HIV vaccine. In 2009, a primeboost vaccine demonstrated an efficacy of 31.2%. This trial, RV144, signaled hope for the future and served as proof of concept that an effective HIV-1 vaccine is possible. Understanding the unique obstacles in HIV vaccine development has been key in creating breakthroughs and tracing a path forward. The complexity of this challenge has required innovative approaches to vaccine development. Future HIV preventive vaccine candidates may target multiple immune pathways. Strategies such as cytotoxic vaccines, envelope targets and antibodies such as broadly neutralizing antibodies or monoclonal antibodies may work in concert to achieve protection from HIV acquisition. An effective HIV preventive vaccine is ever near.

Objective: To evaluate the association of bone turnover biomarkers with blood levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), osteocalcin (OC), tartrate-resistant acid phosphatase (TRAP), parathyroid hormone (PTH), and other blood markers in HIV-1 infected men receiving anti-retroviral therapy (ART). Advances in the treatment of HIV-1 infection have extended the life span of HIV-1 infected individuals. However, these advances may come at the price of metabolic side effects and bone disorders, including premature osteopenia, osteoporosis and osteonecrosis. Methods: Analyses of Ostase BAP, osteocalcin, and TRAP in blood were measured in three groups of MACS participants: 35 HIV-1 infected men on ART (A); 35 HIV-1- infected men not on ART (B); and 34 HIV-1 uninfected men (C). Results: The mean and standard deviation results for groups A, B, and C were 19.7 ± 6.56, 17.2 ± 3.96, and 16.9 ± 5.78 for ostase BAP; 7.9 ± 9.53, 8.5 ± 8.30, and 5.5 ± 1.65 for osteocalcin; and 3.9 ± 1.04, 3.1 ± 0.81, and 2.5 ± 0.59 for TRAP, respectively. Simple and multivariate analyses showed significant differences in mean TRAP and BAP concentrations between the three groups. In addition strong correlations between blood levels of Ostase BAP and TRAP (r=0.570, p=0.0004), and between blood levels of Ostase BAP and PTH (r=0.436, P=0.0098) for HIV-1 infected men on ART were observed. Conclusion: New strategies for measurement of blood and urine biochemical markers of bone formation and resorption during bone turnover can be useful for clinical monitoring of treatment of HIV-1 infected patients. Recently developed methods for measuring serum levels of TRAP and Ostase BAP represent superior laboratory tools for assessing the hyperactivity of osteoclasts, osteoblasts and bone loss in HIV-1 infected individuals receiving ART. Measurements of TRAP and BAP as bone turnover biomarkers are economical and are important for monitoring bone metabolism during ART and the need for osteoporosis treatment.

African Americans in the United States (U.S.) are disproportionately affected by HIV. Developing an HIV vaccine is an important part of the HIV prevention and treatment toolkit and may help contribute to ending the HIV epidemic. To date, HIV vaccine trials have not engaged representative numbers of African Americans. We evaluated the willingness of African Americans to participate in HIV vaccine trials and identified correlates of willingness to participate (WTP) by surveying African Americans at low- and high-risk of HIV infection in a multi-site, cross-sectional study. We enrolled 1,452 participants; 59% heterosexual women; 21% heterosexual men; 20% men who have sex with men (MSM). Over half of participants (58%) expressed some level of WTP in HIV vaccine trials. Multivariable analyses revealed several variables were positively related to WTP: HIV risk behavior, knowing someone with HIV/AIDS, social support for trial participation, high perception of risk, perceived protection if in a trial, altruism, and greater tolerance for the ambiguous nature of trials (p<0.01). Emphasis on contextual factors related to personal HIV experiences, including knowledge of someone with HIV, and community support for research, may provide effective strategies for engaging African Americans in future HIV vaccine trials.

Objective: The aim of this study was to evaluate the association between the PvuII polymorphism in the intron 15 of low-density lipoprotein receptor (LDLR) and dyslipidemia in human immunodeficiency type 1 (HIV-1)-infected individuals. Methods: The study included 355 HIV-1-infected patients [100 antiretroviral-naïve and 255 on highly active antiretroviral therapy (HAART)]. The PvuIILDLR polymorphism was determined using PCR-RFLP methods and the lipid profile was evaluated by serum levels of total cholesterol (COL), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Results: Those patients on HAART showed higher COL, TG, and LDL-C levels than those HAART-naïve (207.0 vs. 175.0 mg/dL, p<0.0001; 167.0 vs. 119.5 mg/dL, p<0.0001, and 124.2 vs. 102.9 mg/dL, p=0.0003, respectively). The frequency of patients with increased levels of COL, TG, and LDL-C was higher among those on HAART than HAARTnaïve (86.6% vs.67.4%, p<0.0001; 80.9% vs. 69.7%, p=0.0380, and 74.4% vs. 62.6%, p=0.0339, respectively). The frequency of the PvuIILDLR genotypes did not differ among the patients according to COL, TG, and LDL-C levels (p>0.05). However, the frequency of high HDL-C levels was higher among those patients carrying the P2P2 genotype (11.8% vs. 5.6%, p=0.0398). Conclusions: The results underscored that HAART are associated with dyslipidemia in some HIV-1-infected patients but not in all of them. Moreover, the results suggest that the P2P2 genotype of the PvuIILDLR polymorphism might be in part modulating the effect of HAART and HIV-1 infectionin HDL-Clevels an

Background: Prevention of mother-to-child transmission of the Human Immuno Virus (HIV) remains an opportunity not to be missed in case future remarkable declines in HIV associated morbidity and mortality are envisaged. Many pregnant women, both in the developed and developing countries today are still received in labor rooms with unknown or redoubtable HIV serostatus. Ethical tensions arising from compulsory (opt in) or consenting (opt out) strategies regarding the labor room HIV testing remain unresolved. Conclusion: This paper presents some neglected and potentially useful avenues that could be exploited especially in high HIV prevalence settings like Sub-Saharan Africa. The authors also highlight key areas for future research.

Cervical dysplasia and cancer are more common and aggressive in HIV-positive women and Papanicolaou (Pap) testing allows for their earlier identification and treatment. Guidelines recommend annual screening for this population. This cross-sectional study assessed prevalence and correlates of self-reported Pap testing among African-Caribbean HIV-positive women who completed an ACASI-administered questionnaire. Participants were recruited through a community health centre in Toronto, Canada. Pap testing history was assessed by a single question asking when the last test was done. Logistic regression examined correlates of Pap testing in the previous year. The 126 participating women’s median age was 40 years (IQR=34-46); 53.2% were East African and 16.7% Caribbean.69.9% and 82.1% of women had received a Pap test in the previous year and three years, respectively; 10.6% had never been tested. Age: 35-49 vs. >50 years (OR=6.7,95%,CI=1.7-25.1), being in Canada for >2 years (OR=4.6,95%,CI=1.6-13.5), having >2 sexual partners (OR=3.4,95%,CI=1.1-10.7) or having seen a family doctor within 6 months (OR=2.6,95%,CI=1.1-6.2) were significantly associated with Pap testing in the past year. In conclusion, 70% of participating women did have Pap screening in the past year. Program development to reach the 30% unscreened women should be sought; especially for the 10% who never received screening.

Background: Individuals with HIV infection commonly have pulmonary function abnormalities, including airflow obstruction and diffusion impairment, which may be more prevalent among recreational drug users. To date, the relationship between drug use and pulmonary function abnormalities among those with HIV remains unclear. Objective: To determine associations between recreational drug use and airflow obstruction, diffusion impairment, and radiographic emphysema in men and women with HIV. Methods: Cross-sectional analysis of pulmonary function and self-reported recreational drug use data from a cohort of 121 men and 63 women with HIV. Primary outcomes were the presence (yes/no) of: 1) airflow obstruction, (pre- or post-bronchodilator forced expiratory volume in 1 second/forced vital capacity<0.70); 2) moderate diffusion impairment (diffusing capacity for carbon monoxide <60% predicted); and 3) radiographic emphysema (>1% of lung voxels <-950 Hounsfield units). Exposures of interest were frequency of recreational drug use, recent (since last study visit) drug use, and any lifetime drug use. We used logistic regression to determine associations between recreational drug use and the primary outcomes. Results: HIV-infected men and women reported recent recreational drug use at 56.0% and 31.0% of their study visits, respectively, and 48.8% of men and 39.7% of women reported drug use since their last study visit. Drug use was not associated with airway obstruction or radiographic emphysema in men or women. Recent crack cocaine use was independently associated with moderate diffusion impairment in women (odds ratio 17.6; 95% confidence interval 1.3-249.6, p=0.03). Conclusions: In this cross-sectional analysis, we found that recreational drug use was common among HIVinfected men and women and recent crack cocaine use was associated with moderate diffusion impairment in women. Given the increasing prevalence of HIV infection, any relationship between drug use and prevalence or severity of chronic pulmonary diseases could have a significant impact on HIV and chronic disease management.

Background: Non-AIDS co-morbidities are emerging as the main health problems for those living with HIV, and primary care for this population is an evolving challenge. Recent studies have raised the question of whether specialists or generalists are best suited to provide HIV primary care, but patients’ actual usage patterns and the preferences of patients and providers have not been well studied. Methods: We anonymously surveyed 98 patients and eight HIV-specialized providers regarding primary care usage patterns and preferences at an academic HIV clinic in Los Angeles that serves insured patients. Results: Fifty-nine percent of patients use their HIV physician as their primary care provider, and 84% would prefer this model. Physicians were divided on their preferred role, with five out of eight desiring to provide both primary care and HIV care. All eight physicians rated their comfort with antiretroviral therapy and opportunistic infections greater than for non-AIDS co-morbidities. Eighty-one percent of patients and seven of eight providers were supportive of having a co-located primary care physician at the HIV clinic. Conclusions: We conclude that patients prefer integration of HIV and primary care, but providers have variable desire to serve as primary care physicians and may be uncomfortable with non-AIDS co-morbidities. This raises the need for improved patient-provider communication about primary care needs, and calls for novel ways of systematically providing primary care to HIV-infected patients.

Background: It has been well established that mother to child transmission accounts for the majority of HIV infections in children below age 15 in developing countries. HIV counselling and testing is an important entry point for HIV prevention and for early access to treatment, care and support. Willingness for accepting HIV counselling and testing is the key component and a starting point of overall HIV prevention efforts and represents a critical opportunity for stemming the tide of the HIV epidemic. Objective: To assess willingness of antenatal care clients for HIV counselling and testing. Methods: Institutional based cross sectional study was conducted on 321 pregnant women attended antenatal care during the study period using interviewer administered, pre-tested, structured questionnaire from March to April, 2012 in Asella governmental health institutions. Data was collected using convenient sampling technique and then entered in Epi-info and analyzed using SPSS software. Result: Among the studied women 291 (90.7%) were willing for HIV counselling and testing. The strongest association rested with parity, number of antenatal care visits and perceived risk of HIV. Primipara women were about 12 times more likely willing for HIV counselling and testing than nullipara mothers (AOR=12.33, 95% CI=1.25,121.57), and also those who had 2 and above antenatal care visits were 9.6 times more likely willing for HIV counselling and testing than those who had only 1 visit (AOR=9.64, 95% CI=1.93,48.28). Women who were perceived themselves not at risk of acquiring HIV were more likely willing for HIV counselling and testing than their counterparts (AOR=0.08, 95% CI=0.01,0.41). Conclusion: This study revealed high-level of awareness about prevention of mother to child transmission of HIV among pregnant women attended antenatal care, and relatively increased proportion of willingness for HIV counselling and testing was seen when compared to other studies.

The pathogenesis of HIV/hepatitis B and/or C co-infection is far from being understood; yet, some studies have shown its relationship with oxidative stress. Because of oxidative stress (conjugated dienes and thiobarbituric acid reactants) and antioxidant defense systems (superoxide dismutase activity, α-tocopherol, reduced and oxidized glutathione) had different parameters in 26 women with HIV-monoinfection and 27 women with HIV/hepatitis B and/or C co-infection (with no signs of AIDS), they were evaluated. Spectral fluorofotometric methods were used. Statistical analysis was performed by parametric and non-parametric methods. The evaluation found that while conjugated dienes levels were significantly higher, superoxide dismutase (SOD) activity and α-tocopherol levels were significantly lower in women with HIV/hepatitis B and/or C co-infection than in those with HIV-monoinfection. Concurrently, during the highly active antiretroviral therapy (HAART), conjugated dienes, thiobarbituric acid reactants mean levels were lower; SOD activity and α-tocopherol levels were higher in HIV-monoinfected patients than in those with HIV/hepatitis B and/or C co-infection (with no signs of AIDS). This outcome was characterized by more expressed oxidative stress.

Introduction: HIV testing and counseling is associated with reduction in risk behavior. Not all persons who receive pretest counseling and testing return for posttest counseling. Hence, it is imperative to identify positive clients when they first come for testing. Objectives: To determine demographic profile of HIV positive clients visiting our centre. Methods: Data obtained by HIV testing of clients from January 2012 to December 2012 was analyzed. Age, gender, education, occupation and marital status were evaluated as independent variables. Analysis consisted of descriptive data of frequency tables, means, confidence intervals and multinomial logistic regression analysis. Results: A total of 14,239 individuals were tested for HIV antibodies. Eight samples were excluded from analysis. 987(6.94%) samples tested positive. As compared to individuals with age above 50 years, those in the age group of 35-49 and 25-34 years had 2.6 and 1.4 times more chance of being positive respectively. Males had 1.6 times more chance of being positive than females. Non-literate had 2.2 times more chance of being positive than individuals who had education more than 10th standard. Daily wage workers from the low socio economic group had 1.5 times more chance of being positive than housewives. As compared to married individuals, divorcee/separated and widow/er had more than four times chance of being positive. A direct walk in client had 12 times more chance of being positive as compared to referred patients. Conclusions: In our patient population, a direct walk in male client in the age group of 25 to 49 years who is not much educated, a daily wage worker and who is either separated/divorced/widow/er has a significantly higher risk of being positive. He should be tested, reported, counseled for behavioral change and practicing safe sex and linked to care and support program preferably on the same day.

Background: Clinical characteristics of HIV-1 infection in people inhabiting Western, Sub-Saharan African, and South-East Asian countries are well recognized. However, very little information is available with regard to HIV-1 infection and treatment outcome in MENA countries including the Gulf Cooperation Council (GCC) states. Methods: Clinical, demographic and epidemiologic characteristics of 602 HIV-1 infected patients followed in the adult Infectious Diseases Clinic of King Faisal Specialist Hospital and Research Centre, in Riyadh, Kingdom of Saudi Arabia a tertiary referral center were longitudinally collected from 1989 to 2010. Results: Of the 602 HIV-1 infected patients in this observation period, 70% were male. The major mode of HIV-1 transmission was heterosexual contact (55%). At diagnosis, opportunistic infections were found in 49% of patients, most commonly being pneumocysitis. AIDS associated neoplasia was also noted in 6% of patients. A hundred and forty-seven patients (24%) died from the cohort by the end of the observation period. The mortality rate peaked in 1992 at 90 deaths per 1000 person-year, whereas the mortality rate gradually decreased to <1% from 1993-2010. In 2010, 71% of the patients were receiving highly active retroviral therapy. Conclusions: These data describe the clinical characteristic of HIV-1-infected patients at a major tertiary referral hospital in KSA over a 20-year period. Initiation of antiretroviral therapy resulted in a significant reduction in both morbidity and mortality. Future studies are needed in the design and implementation of targeted treatment and prevention strategies for HIV-1 infection in KSA.

Background: Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. Methods: This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1- infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Results: Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Conclusions: Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Background: We investigated whether tolerance and durability were different according to the presence or absence of co-infection (hepatitis B and/or hepatitis C virus) among a cohort of HIV-1 patients treated with fosamprenavir/r (FPV/r) containing regimen. Methods: Data were collected from 7 large HIV reference medical centers in France. We selected adult HIV-1 infected patients who were receiving an antiretroviral combination including FPV/r between January 2004 and December 2007. Date and reason for FPV/r discontinuation were recorded. Time to treatment discontinuation was analyzed by Kaplan Meier survival method. Results: In total, 1279 patients treated with FPV/r containing regimen were analysed in the study period out of them 20% were ART (antiretroviral therapy)-naive. 460 patients were hepatitis co-infected (13% are ART naive), 74% with HCV, 17% with HBV, 6% both. 263 co-infected patients (57.2%) and 469 mono-infected patients (57.2%) discontinued the FPV/r-including regimen after a median duration of 23 months, with no difference between coinfected and non-co-infected patients, at 23.2 months (95% CI 19.3-27.7) and 23.0 months (95% CI 20.3-25.5), respectively. Tolerability issues were the main reason for early discontinuation and among them gastro-intestinal (GI) adverse effects were the most frequent. Conclusion: In summary, antiviral therapy including FPV/r provides similar durability in HIV/HCV or HBV coinfected patients as in HIV mono-infected patients, for both naïve and experienced patients.

Objective: Zidovudine, the first antiretroviral drug is used to prevent vertical transmission of HIV infection. Without any adequate proof of its safety to fetus, the drug was administered to pregnant women. The present experiment aims to study at the light microscopic level, the effect of zidovudine in fetus exposed in-utero to the drug. Material and method: Sixty Swiss mice were divided into two groups of control (n=20) and experimental (n=40). A dose of 50 mg/kg/day was administered orally to experimental group and an equivalent amount of normal saline to control group. Drug was administered from day 8 to day 16 of gestation and on day 19 the animal was sacrificed. Fetus collected after laparotomy were fixed in 10% neutral formalin and then subjected to light microscopic study to assess the histopathological changes. H&E stained sections of liver, lung, kidney, brain and maternal ovary was analysed. Result: Fatty degeneration of liver, degenerative changes in kidney section, dilatation of alveoli with thinning of alveolar wall, microcystic degeneration in cerebral cortex was observed. The maternal ovary of experimental group had small corpus luteum. Conclusion: Multiple tissues are affected by in-utero administration of ZDV. Further study at ultrastructural level is needed.

Background: Children and adolescent, who acquire HIV infection early in life either perinatally, from contaminated blood products or via sexual transmission, have the greatest cumulative exposure to the negative direct and indirect effects of HIV infection and ART on bone. This may lead to increased lifetime risk for osteoporosis and fracture. We conducted a systematic review to evaluate the literature on bone health in children and adolescents with HIV. Methods: We performed a comprehensive search of the Medline, Scopus, and Cochrane Library databases (up to April 1, 2014) for studies that reported on bone imaging or bone fractures in HIV-infected children, adolescents, or young adults. Results: A total of 32 publications met our inclusion criteria. Seventeen studies were cross-sectional and 15 were longitudinal. The majority of studies were conducted in high-income countries, three in middle-income countries and none in low-income countries. Overall, the studies we reviewed indicate that measures of bone mass are reduced, with increased prevalence of low BMD in children and adolescents with HIV. However, the studies are highly variable with respect to comparison sources, measurement methods, adjustment techniques for body size or growth retardation, and highlighted risk factors, including aspects related to medication exposures as well as the effects of HIV infection per se. Conclusions: HIV infection appears to be associated with decreased bone accrual throughout childhood and adolescence. Sub-optimal bone accrual may persist through childhood and adolescence and result in reduced peak bone mass, an important determinant of future risk of osteoporosis and fracture. Important areas for future research include evaluation of bone mass, bone quality and fracture risk across the life course among those with early-life infection with HIV, particularly in resource-limited settings where the majority of children with HIV live.

Objective: HIV-infected patients still experience higher Cardiovascular (CV) mortality rates, even if an adequate viral suppression is achieved. In addition, vitamin D insufficiency, a common condition in HIV-infected patients, is increasingly associated with CV risk. We therefore aim to investigate relationships between immunological parameters, antiretroviral therapy, plasma vitamin D and arterial parameters, including aortic stiffness and wave reflections, in HIV-infected patients who achieved viral suppression but possibly remain at increased CV risk. Methods: We conducted a cross-sectional study including 178 middle-aged HIV-infected patients. HIV infection was controlled in a large number of participants, representative of a real-world setting. In addition to carotid Intima Media Thickness (IMT), central hemodynamic parameters involved aortic Pulse Wave Velocity (PWV), carotid Augmentation index (AIx) and Pulse Pressure Amplification (PPA) measured noninvasively using applanation tonometry. Results: Aortic PWV was slightly but unsignificantly higher than the theoretical values obtained in general population according to age and blood pressure, and was independent of HIV-related parameters. In univariate and multivariate analyses, carotid AIx was positively correlated with current CD4 T-cell count and PPA was positively correlated with vitamin D, independently of other confounders. No HIV-related parameters or vitamin D entered the multivariate analysis of carotid IMT / plaque. Conclusion: In our chronically treated population, HIV infection was not associated with increased aortic stiffness but with a positive correlation between current CD4 T-cell count and degree of AIx, suggesting that patients with higher CD4 T-cell count may have higher wave reflections. The positive correlation between vitamin D and PPA suggests that vitamin D deficiency may be independently associated with altered central hemodynamics in well controlled HIV-infected patients. These findings should be confirmed in prospective studies.

This paper examines the association between intimate partner violence and the consistency of condom use in a US urban cohort of HIV-serodiscordant couples. It uses both male and female data from the California Partners Study II of a lower-income ethnically mixed cohort of 145 such couples in the San Francisco Bay Area. We observed a significant association between inconsistent condom use and physical abuse and forced sex: the risk of inconsistent condom use was double for those experiencing physical abuse (OR, 2.2; 95%CI, 1.1, 4.1). Injection drug use and a history of bisexual behavior were also associated with inconsistent condom use. Physical abuse tended to be reciprocal between partners (OR, 3.2; 95% CI, 1.9, 5.6). Our findings suggest that interventions effective in reducing intimate partner violence, and/or reducing the use of injection drugs in HIV-serodiscordant couples could lead to less transmission of HIV.

Complex patients with multiple comorbidities are rarely included in large randomized studies. As a result, little is known about the optimal management of these cases. The following two cases occurred within a six month period in 2013 and were seen at Casey House, a community-based facility specializing in HIV/AIDS in Toronto, Canada. Both cases involved a serious assault to the liver believed to be drug induced liver injury (DILI) caused by darunavir. In the first case, Patient A, a 50 year-old male with a CD4 count of 454 cells/mm3 presented with tense ascites, jaundice and pedal edema. He had recently started a new anti-retroviral combination including darunavir. The ARV medications were stopped, liver function improved and his ascites was reduced with paracentesis and infusions of albumin. Chronic hepatitis B was identified. The patient was started on a new anti-retroviral regimen effective for hepatitis B. His liver failure resolved and he continues to live well in the community. In Patient B, a 49 year-old woman with CD4 count of 20 cells/mm3 and Mycobacterium Avium Complex (MAC) and hepatitis C was started on a darunavir-based regimen. She developed abdominal pain, jaundice, elevated liver function tests and anemia. HIV medications were held, and then restarted. Her symptoms worsened. Eventually all medications were stopped. Although the patient’s liver began to recover, her CD4 count remained very low and the patient developed pneumocystis pneumonia (PJP) and died. These cases are presented with a view to better understanding darunavir and its potential toxicity. The literature concerning darunavir toxicity in the setting of complex comorbidity will be reviewed.

Objective: Integrase (IN) is an enzyme essential for HIV-1 replication that has been a target of antiretroviral drug therapy. Since emerging HIV-1 variants have frequently become clinically resistant to antiretroviral agents, it is necessary to develop alternative IN inhibitors. Methods: We tested IN inhibitors, M522 and M532, against clinically resistant HIV-1 strains to antiretroviral drugs (AZT, non-nucleoside reverse transcriptase inhibitors, IN drug raltegravir, protease inhibitors); wild-type and clinical isolate from HIV-infected patients. We performed disintegration studies to show the interaction of M522 and M532 with the catalytic core domain of HIV-1 IN and time-of-drug-addition experiments to determine the inhibition step of viral replication. We tested selection of HIV-1 with M522 and M532 to examine the emergence of new drug resistant virus. CD4+ cell count was calculated for several groups of cells infected with HIV, cells treated and non-treated with M522 and M532 to evaluate their protective effect. Results: M522 and M532 inhibited the replication of HIV-1 strains (wild-type; drug-resistant; clinical isolate from infected patients; and laboratory strains) with high potency. These inhibitors interacted with the catalytic core domain of HIV-1 IN and blocked its activity, prevented viral integration. M522 and M532 interfered with the viral replication precisely at the integration step. HIV-1 virus did not develop resistance to M522 and M532 for 20 viral passages (160 days). These IN inhibitors protected the infected cells from cytopathic effects and the CD4+ cell counts of these cells treated with M522 and M532 were found to be identical to those of the uninfected cells. Conclusion: M522 and M532 are potent against clinical isolate from HIV-infected patients, wild-type and clinically resistant strains especially the relevant raltegravir-resistant virus. Development of M522 and M532 as new mutationinsensitive drugs aiming for the protection of CD4+ T-cells during HIV infection in the clinical trials is in progress.

Background: Tenofovir associated nephrotoxicity (TDFN) is well recognized. This study describes the trend of renal function recovery and virologic consequences after cessation of tenofovir (TDF) for suspected TDFN. Methods: This was a retrospective chart review of 241 patients who underwent HLA-B*5701 allele testing between January 2007-December 2010. Demographics and clinical characteristics were compared at baseline, 3, 6, and 12 month between patients that continued and discontinued TDF. Factors associated with renal function recovery were assessed by multivariable logistic regression. Results: Eighty patients were identified with TDFN; 84% male, 74% African American (AA) with a median age of 55 years, and median length of TDF use for 122 weeks. Renal recovery at 12 months differed in those who stopped versus (vs.) continued TDF (83% vs. 57% p=0.03). In a crude analysis, baseline chronic kidney disease was negatively associated with renal recovery (p=0.01). An adjusted analysis showed that those who stopped TDF had 3.76 higher odds of renal recovery compared to those who did not stop TDF (95% CI: 1.26-11.27, p=0.02). There were no significant differences in virologic response after switching TDF to an alternative agent. Conclusion: In this mostly AA male population with suspected TDFN, discontinuation of TDF was strongly associated with renal function recovery without affecting viral suppression.