Natural History Of HIV Infection Research Articles

A potential transition from a concentrated to a generalized HIV epidemic: the case of Madagascar

BackgroundHIV expansion is controlled by a range of interrelated factors, including the natural history of HIV infection and socio-economical and structural factors. However, how they dynamically interact in particular contexts to drive a transition from concentrated HIV epidemics in vulnerable groups to generalized epidemics is poorly understood. We aim to explore these mechanisms, using Madagascar as a case-study.MethodsWe developed a compartmental dynamic model using available data from Madagascar, a country with a contrasting concentrated epidemic, to explore the interaction between these factors with special consideration of commercial and transactional sex as HIV-infection drivers.ResultsThe model predicts sigmoidal-like prevalence curves with turning points within years 2020–2022, and prevalence reaching stabilization by 2033 within 9 to 24% in the studied (10 out of 11) cities, similar to high-prevalence regions in Southern Africa. The late/slow introduction of HIV and circumcision, a widespread traditional practice in Madagascar, could have slowed down HIV propagation, but, given the key interplay between risky behaviors associated to young women and acute infections prevalence, mediated by transactional sex, the protective effect of circumcision is currently insufficient to contain the expansion of the disease in Madagascar.ConclusionsThese results suggest that Madagascar may be experiencing a silent transition from a concentrated to a generalized HIV epidemic. This case-study model could help to understand how this HIV epidemic transition occurs.Graphical abstract

Incidence and Clinical Description of Lymphomas in Children and Adolescents with Vertical Transmission of HIV in Rio de Janeiro, Brazil, in Pre- and Post-Combined Antiretroviral Therapy Eras: A Multicentric Hospital-Based Survival Analysis Study.

The incidence of cancer in children living with HIV (CLWH) is high and lymphomas are the most common type of cancer in this population. The combined antiretroviral therapy (cART) changed the natural history of HIV infection. To determine the incidence and profile of these CLWH malignancies in Rio de Janeiro (RJ), Brazil, we conducted a retrospective and observational study of vertically infected CLWH, ranging from 0-20 incomplete years, from 1995 to 2018, at five reference centers. The study period was divided into three eras in accordance with the widespread use of cART in Brazil. 1306 patients were included. Of the 25 lymphomas found, 19 were AIDS-defining malignancies (ADM); 6 were non-AIDS-defining malignancies (NADM). The incidence rate (IR) of lymphoma developing was 1.70 per 1000 children-year (95% CI 1.09-2.50). ADM development IR decreased from 2.09-1.75-0.19 per 1000 children-year (p < 0.001) through cART eras. Cumulative Nelson-Aalen hazards of developing ADM over a 20-year period were 3.73% in the Early-cART era, 3.07% in the Mid-cART era, and 0.32% in the Late-cART era (p = 0.013). This study demonstrates the IR of lymphoma in CLWH in RJ, Brazil, as well as the benefit of cART in reducing ADM and death occurrence in the Post-cART era.

Monkeypox vaccination—an opportunity for HIV prevention

Monkeypox vaccination—an opportunity for HIV prevention

LIVER TRANSPLANTATION IN HIV PATIENTS: A CASE SERIES FROM THE NORTHEAST REGION OF BRAZIL.

The emergence of potent combined highly active antiretroviral therapy (ART) in 1996 changed the natural history of HIV infection, with a significant reduction in mortality due to opportunistic infections but increased morbidity due to chronic cardiovascular, hepatic, and renal diseases. In May 2016, a reference center for liver transplantation in the Northeast of Brazil performed the first liver transplantations (LT) in HIV patients, with five others until 2021. The criteria for selection of LT were good adherence and absence of resistance to ART, HIV viral load maximum suppression, T-CD4+ lymphocyte count of more than 100 cells/mm3, and absence of opportunistic infections in the last 6 months. Six liver transplants were performed between May 2016 and May 2021, five men, with a mean age of 53.2 years, and one was a diabetic patient. All patients had access to grafts with short cold ischemia with a mean time of 5 hours and 39 minutes. The 4-month survival rate was 100%, with a range time of follow-up of 4-63 months (mean time of 31 months). The mean pre-transplant T-CD4+ lymphocyte count was 436 cells/mm3. The mean length of hospital stay after transplantation was 16.8 days. One patient presented precocious vena cava thrombosis; another had stenosis of cavocaval anastomosis leading to refractory ascites, renal failure and post-transplant graft dysfunction, and another presented stenosis of choledochal anastomosis. Immunosuppression and prophylaxis were used according to standard protocols, and there were no differences in the profile of infections or rejection after liver transplantation. This case series documents good survival and usual transplant procedures for confirmed HIV cases.

Clonal Hematopoiesis Is More Common in People Living with HIV and May be Associated with Increased Prevalence of Cardiovascular Disease

Background: Cardiovascular disease (CVD) is more common in people living with HIV (PLWH) and may be related to abnormal immune activation. With aging, the expansion of mutated hematopoietic clones or clonal hematopoiesis (CH) has been associated with CVD events in the general population and is hypothesized to be driven by systemic inflammation. We investigated whether CH was more common in PLWH compared to those without HIV, whether the distribution of CH mutations differed by HIV status, and whether CH was associated with subclinical coronary atherosclerosis in PLWH.Methods: Study participants were selected from men in the Baltimore -Washington DC center of the Multicenter AIDS Cohort Study (MACS) who had had coronary CT angiography (CTA) as part of the MACS Cardiovascular Study 2. The MACS is a prospective study of the natural history of HIV infection in men who have sex with men, and includes both PLWH and HIV-uninfected men. Since the prevalence of CH increases with age, the oldest participants were preferentially included in this study. To detect CH, DNA extracted from viably frozen peripheral blood mononuclear cells or cell pellets was subjected to targeted, error-corrected, ultra-deep next generation sequencing (NGS) which included 70 genes frequently mutated in hematologic malignancies. CTA results and inflammatory biomarker levels were already available from MACS data.Results: The current analysis was a cross-sectional study involving 118 participants: 86 (72.9%) PLWH and 32 (27.1%) HIV-uninfected men (HIV-). The groups were well-balanced in terms of known major risk factors for CH such as age and smoking. The median age was 53 and 54 years for PLWH and HIV- men, respectively (p=0.147). Caucasians represented 37 (43.0%) of PLWH and 21 (65.6%) of HIV- men. Out of 86 PLWH, 72 (83.7%) were on antiretroviral therapy (ART) at the time of the assessment; 41 (47.7%) on a PI-containing regimen and 31 (36.0%) on an NNRTI-containing regimen. The HIV viral load was under 400 copies/mL in 77 (89.5%) of PLWH, and the median (IQR) CD4+ count was 585 (397, 745)/mL. The prevalence of coronary artery stenosis of 50% or more was 12 (14.3%) in PLWH and 5 (16.1%) in HIV- men (p = 0.774).Since the minimum size of the biologically relevant CH is unknown, we applied variant allele frequency (VAF) cut-offs of > 0.5% and > 1%. For both cutoffs, CH was significantly more frequent in PLWH than in HIV- men (p=0.012 and p=0.036, respectively) (Figure 1A). Mutations in epigenetic modifiers (DNMT3A, TET2) were the most common mutations among both PLWH and HIV- men. Interestingly, DNMT3A mutations were more frequent in PLWH (Figure 1B). For both VAF cut-offs, PLWH had significantly more somatic mutations than HIV-uninfected men (p = 0.043 and 0.033, respectively) (Figure 1C).Since inflammation-mediated complications of CH become more apparent in people with larger clones, we focused on CH with VAF > 1% in order to determine the clinical consequences of CH in PLWH. As CH is known to be a risk factor for accelerated CVD in the general population, we asked whether CH was also associated with subclinical atherosclerosis in PLWH. Coronary artery stenosis > 50% (moderate/severe) was significantly more frequent in PLWH with CH compared to PLWH without CH (p = 0.032) (Figure 1 D). This difference remained significant in multivariable logistic regression models that adjusted for the Framingham coronary heart disease 10-year risk (p=0.017) and for the Framingham hard coronary heart disease 10-year risk (p<0.01).Additionally, we examined the association of serum concentrations of several inflammatory markers such as CRP, IL-1b, IL-6, as well as white blood cell count, with the presence of CH in PLWH, but we found no significant associations.Conclusions: CH was more common in PLWH compared to HIV-uninfected men, and PLWH had more somatic mutations. Moreover, the presence of CH was significantly associated with the presence of coronary artery stenosis > 50% (moderate/severe) in PLWH, even after adjusting for known CVD risk factors. The results from our exploratory analysis may provide a potential explanation for increased CVD in PLWH. Larger studies are warranted to further delineate the etiology of increased CH in PLWH and its impact on accelerated CVD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical and immunological characteristic and dynamic of the secondary diseases stage of HIV infection in children, taking into account the route of infection

The purpose is to characterize the clinical picture, immune status and the natural history of HIV infection in the stage of secondary diseases in vertical and parenteral infected children.Materials and methods. A clinical, laboratory, instrumental, immunological examination of 132 children in the stage of secondary diseases infected with HIV in a vertical way (90; I group) and parenteral way in infancy (42; II group) was carried. Results. The clinical picture of HIV infection in the stage of secondary diseases included various combinations of HIV-associated symptoms, opportunistic infections, tumors, which determines the symptomatology of a particular stage. The use of the Cox regression mathematical model of proportional intensities demonstrated a reduction in the duration of stage 4A (RR 5.8; 95% CI 1.4—10.5; P &lt; 0.001), 4B (RR 3.4; 95% CI 1.8—4.3; P &lt; 0.001) and 4V (RR 4.8; 95% CI 1.2—8.9; P &lt; 0.001) in children of group I. Using the method of multiplying Kaplan-Meier estimates, the significant differences between the time curves from the beginning of the 4A stage (Р = 0.044), 4B (P &lt; 0.001) and 4V (Р = 0.029) before the transition to the subsequent stage in children of groups I and II were established. The content of CD4 lymphocytes in the blood in patients of group I was higher as compared with group II at the time of debut of stages 4A (Me 37.5%, IQI 33—40% and Me 22%, IQI 18—24%; Р &lt; 0.001), 4B (Me 25%, IQI 22—28% and Me 20%, IQI 18—22%; Р &lt; 0.001) and 4V (Me 14%, IQI 12—18% and Me 11%, IQI 10—14%; Р = 0.047).Conclusion. HIV infection in the stage of secondary diseases in children infected with the vertical way is characterized by more rapid progression compared with parenteral infected in infancy patients, which is associated with the immaturity of the immune system.

HIV-1 and human genetic variation.

Over the past four decades, research on the natural history of HIV infection has described how HIV wreaks havoc on human immunity and causes AIDS. HIV host genomic research, which aims to understand how human genetic variation affects our response to HIV infection, has progressed from early candidate gene studies to recent multi-omic efforts, benefiting from spectacular advances in sequencing technology and data science. In addition to invading cells and co-opting the host machinery for replication, HIV also stably integrates into our own genome. The study of the complex interactions between the human and retroviral genomes has improved our understanding of pathogenic mechanisms and suggested novel preventive and therapeutic approaches against HIV infection.

Short Communication: HIV Viral Load Trends During the Coronavirus Disease 2019 Pandemic in a Reference Center for HIV in Rome, Italy.

Coronavirus disease 2019 (COVID-19) pandemic has reduced the access of HIV patients to reference centers. However, retention-in-care is critical to maintain adherence to therapy and viral suppression. During lockdown in Italy, our center implemented several measures to ensure HIV-care continuum. To assess whether these efforts were successful, we investigated HIV viral load trend for a 1-year period (September 2019-August 2020), which included lockdown and partial lockdown months in our country. No significant changes overtime in the proportion of undetectable HIV-RNA were observed. Continuity of service made it possible to maintain viral suppression in our patients.

Pregnancy outcomes in sexually transmitted infections or human immunodeficiency viruses infected women at a tertiary care center: a retrospective study

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The natural history of HIV infection in early disease is not affected by pregnancy. In later stages there may be rapid disease progression leading to adverse pregnancy outcomes. Prevalence of HIV in India is 0.3% in pregnant women. With the advent of PPTCT, there have been a decline in the adverse pregnancy outcomes but still few adversities are reported. Aim of the study was to assess the various pregnancy outcomes in HIV positive women and the effects of antiretroviral therapy (ART).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective analytical study conducted from July 2017-June 2019 on HIV infected pregnant women. Their maternal age, CD4 count at diagnosis of HIV, after postpartum, mode of delivery, birth weight and HIV status of baby were noted and analyzed. &lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;18 HIV infected pregnant women were included. Their mean age was 25.6 years. 12 patients were in 2&lt;sup&gt;nd&lt;/sup&gt; trimester and the rest in 1&lt;sup&gt;st&lt;/sup&gt; trimester. All were on triple-drug (TEL) regimen. Three were diagnosed with HIV prior to conception and were already on ART. Remaining were detected at the time of ANC visit. All cases fall under stage I WHO clinical staging. Out of the 18 pregnant, two delivered by LSCS and the rest by normal delivery. All were term deliveries, with mean birth weight of 2.82 kg. One HIV infected baby was born by LSCS. The mean CD4 count at the time of diagnosis of HIV was 389 and at postpartum was 508. Overall, there was seen to be an increase in CD4 count without any adverse effects during ART.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Prompt HIV diagnosis and ART initiation during antenatal period can have good pregnancy outcome and thereby reducing transmission to children.&lt;/p&gt;

Metabolic Syndrome and Myocardial Involvement in HIV-Infected Patients

Abstract The current HAART has modified natural history of HIV infection and it has practically turned the disease into a manageable chronic condition. Even though the benefits of HAART use are overwhelmingly greater than possible metabolic syndrome and cardiovascular disease risks, close management of those patients is called for, especially due to the fact that general population risk factors now overlap with specific ones in this population. Cardiovascular screening for HIV-infected patients who are receiving HAART must be done constantly with a collaboration between the infectious disease specialist and the internist.

Increasing contribution of integrated forms to total HIV DNA in blood during HIV disease progression from primary infection.

BackgroundIn the current context of research on HIV reservoirs, offering new insights into the persistence of HIV DNA in infected cells, which prevents viral eradication, may aid in identifying cure strategies. This study aimed to describe the establishment of stable integrated forms among total HIV DNA during primary infection (PHI) and their dynamics during the natural history of infection.MethodsTotal and integrated HIV DNA were quantified in blood from 74 PHI patients and 97 recent seroconverters (<12 months following infection, “progression cohort”). The evolution of both markers over six years was modelled (mixed-effect linear models). Their predictive values for disease progression were studied (Cox models).FindingsFor most patients during PHI, stable integrated forms were a minority among total HIV DNA (median: 12%) and became predominant thereafter (median at AIDS stage: 100%). Both total and integrated HIV DNA increased over a six-year period. Patients from the progression cohort who reached clinical AIDS during follow-up (n = 34) exhibited higher total and integrated HIV DNA levels at seroconversion and a higher percentage of integrated forms than did slower progressors (n = 63) (median: 100% vs 44%). The integrated HIV DNA load was strongly associated with the risk of developing AIDS (aRR = 2.63, p = 0.002).InterpretationThe profile of “rapid” or “slower” progression in the natural history of HIV infection appears to be determined early in the course of HIV infection. The strong predominance of unstable unintegrated forms in PHI may explain the great benefit of this early treatment, which induces a sharp decrease in total HIV DNA.FundFrench National Agency for Research on AIDS and Viral Hepatitis.

In memoriam

In memoriam

AIDS-Associated Malignancies.

Malignancies were one of the earliest recognized manifestations that led to the description of the acquired immune deficiency syndrome (AIDS). Themajority of cancers in AIDS patients are associated with coinfection with oncogenic viruses, such as Epstein-Barr virus, human herpesvirus 8, and human papillomavirus, with resulting malignancies occurring secondary to diminished immune surveillance against viruses and virus-infected tumor cells.Over 50% of AIDS lymphomas are associated with Epstein-Barr virus (EBV) and/or HHV8 infection. HHV8-associated diseases include Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). EBV is associated with several malignancies, including Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Coinfection with HIV and HPV is associated with an increased risk of various squamous cell carcinomas of epithelial tissues. HAART has significantly impacted the incidence, management, and prognosis of AIDS-related malignancies. In addition to changing the natural history of HIV infection in regard to incidence and survival, HAART has dramatically decreased the incidence of certain virally mediated HIV-associated malignancies such as KS and primary CNS lymphoma. The beneficial effects of HAART on these tumors are attributed to drug-mediated HIV suppression and immune reconstitution. However, HAART has had a less favorable impact on EBV- and HPV-related malignancies. This chapter presents an overview of HIV-associated malignancies mediated by HHV-8, EBV, and HPV, and reviews the effect of HAART on the epidemiology, presentation, treatment, and outcomes of these cancers.

Rapid emergence of cryptococcal fungemia, Mycobacterium chelonae vertebral osteomyelitis and gastro intestinal stromal tumor in a young HIV late presenter: a case report

BackgroundHighly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality. Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management.Case presentationA 35-year-old male with a history of fever and back pain. HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm3). Imaging investigations revealed multiple vertebral and pulmonary lesions together with abdominal and thoracic lymphadenopathy. Blood cultures were positive for Cryptococcus neoformans and for Staphylococcus haemolyticus.Lymphnode biopsy resulted positive in PCR for Non-Tuberculosis Mycobacteria (Mycobacterium chelonae). A gastric biopsy also revealed a GIST. The patient also had CMV DNA positive. Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome.ConclusionThe reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed.Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with. In spite of proper management, the risk of suboptimal results cannot be excluded.

I-101 The changing natural history of HIV infection: From opportunistic infections to inflammation and chronic diseases

Clinicians are well aware of the changing natural history of HIV infection in regions where antiretroviral therapy is accessible. Clinical investigations of HIV in the first 20 years of the epidemic focused on the diagnosis, treatment and prevention of opportunistic infections. While there has always been a need to improve management strategies, effective approaches were developed for most opportunistic infections, although the quality and duration of survival were short until antiretroviral therapy became effective and durable. As patients have live longer, morbidity due to comorbidities related to viral diseases (HCV, HBV, HPV, CMV), metabolic disorders, chronic inflammation, and neoplastic processes have become more prevalent. Health care systems have had to augment and expand their screening programs for such morbidities, and develop more comprehensive health care for HIV infected patients who survive with these co morbidities. Washington, D.C. is an example of a city which is realigning its resources to focus on these emerging comorbidities and to integrate care. Data on these comorbidities provide insight into research challenges that must be met.

A Study of the Longitudinal Patterns of Stimulant and Amyl Nitrite Use and Sexual Behavior Pre- and Post-HIV Seroconversion Among MSM.

The use of stimulant drugs alone or in combination with amyl nitrites (stimulant/nitrites) has been associated with higher rates of risky sexual behavior and predictive of HIV infection among men who have sex with men. However, the temporal pattern of stimulant/nitrite use pre- and post-seroconversion has not been well established. This study assessed changes in stimulant/nitrite use and risky sexual behavior among seroconverting MSM over time. Data were collected in the Baltimore-Washington, DC; Pittsburgh; Chicago; and Los Angeles sites of the Multicenter AIDS Cohort Study (MACS), a longitudinal study of the natural history of HIV infection among MSM. We used propensity scores to select 1044 MSM from 7087 MACS participants composed of 348 seroconverting, 348 seronegative, and 348 seroprevalent participants matched on demographics, recruitment cohort, and study visits. We centered up to four-years of semi-annual data around the seroconversion visit of the seroconverting case within each matched group of participants. Mixed effects regressions estimated the effects of serostatus, recruitment cohort, and time on self-reported stimulant/nitrite use, numbers of male intercourse partners, and numbers of unprotected receptive anal intercourse (URAI) partners. Covariates included demographics, binge drinking, and marijuana use. Seroconverters had the highest odds of stimulant/inhaled nitrite use (AOR 10.3, CI 4.8-22.0), incident rates of intercourse (IRR 1.6, CI 1.3-2.1), and URAI partners (IRR 5.1, CI 3.5-7.3). All participants decreased drug use and sexual risk behavior over time. However, the decreases were largest for seroconverters who nevertheless maintained the highest rates of stimulant/nitrite use and sexual risk. Cohort-related effects were associated with sharp reductions in stimulant/nitrite use and URAI in the early 1990s that rebounded considerably within the first decade of the 2000s. Although all participants decreased risky sexual behavior and stimulant and/or nitrite use over time, seroconverters had the largest decreases. There was no evidence for abrupt or substantial increases in drug use or risky sex post-seroconversion. However, there was substantial variation at the individual level, with the factors underlying this variation not well understood and worth further study. Moreover, stimulant/nitrite use and risky sexual behavior appear to have been strongly influenced by contextual historical and socio-cultural effects. The manner in which contextual factors influence individual behavior is also not well understood and also warrants further study.

Hospitalization causes and outcomes in HIV patients in the late antiretroviral era in Colombia

BackgroundAntiretroviral therapy (ART) has modified the natural history of HIV-infection: the incidence of opportunistic infections (OIs) has decreased and mortality associated to HIV has improved dramatically. The reasons for hospitalization have changed; OIs are no longer the most common reason for admission. This study describes the patient population, admission diagnosis and hospital course of HIV patients in Colombia in the ART era.MethodsPatients admitted with HIV/AIDS at six hospitals in Medellin, Colombia between August 1, 2014 and July 31, 2015 were included. Demographic, laboratory, and clinical data were prospectively collected.Results551 HIV-infected patients were admitted: 76.0% were male, the median age was 37 (30–49). A new diagnosis of HIV was made in 22.0% of patients during the index admission. 56.0% of patients of the entire cohort had been diagnosed with HIV for more than 1 year and 68.9% were diagnosed in an advanced stage of the disease. More than 50.0% of patients had CD4 counts less than 200 CD4 cells/μL and viral loads greater than 100,000 copies. The main reasons for hospital admissions were OIs, tuberculosis, esophageal candidiasis and Toxoplasma encephalitis. The median hospital stay was 14 days (IQR 8–23). Admission to the intensive care unit (ICU) was required in 10.3% of patients and 14.3% were readmitted to the hospital; mortality was 5.4%.ConclusionsSimilar to other countries in the developing world, in Colombia, the leading cause of hospitalization among HIV-infected patients remain opportunistic infections. However, in-hospital mortality was low, similar to those described for high-income countries. Strategies to monitor and optimize the adherence and retention in HIV programs are fundamental to maximize the benefit of ART.

Preliminary study on screening for proteinuria using urine test strips in patients living with HIV at Fann's CHNU in Dakar

Glomerulopathy and other kidney disorders are frequent during the natural history of HIV infection even if their incidence decreased with HAART. They are almost always responsible of proteinuria and/or hematuria. We have conducted a preliminary study on the prevalence of proteinuria screened by urinary strip in PLWHIV followed up at the clinic of infectious diseases at Fann teaching hospital in Dakar. It was a prospective study from August 1st to October 30th, 2008. We enrolled all patients both indoor and outdoor positive for HIV presenting a proteinuria without concurrent urinary infection. We collected sociodemographic data, natural history, factors related to proteinuria and nephropathy. Data entering and analysis were done using Epi Info version 6.04 software. We have used Chi square test to compare qualitative variables and p&lt;0.05 was set as significant threshold. A total of 100 patients were enrolled, the mean age was 43± 9.8 y/o in male and 39± 10 y/o in female. Females were predominant (sex ratio M/F is 0.5). All patients were infected by HIV1, they have been diagnosed at a late stage of immunodeficiency, fifty percent was taking HAART, and the majority using AZT +3TC+ EFV regimen. The prevalence of proteinuria was 47.0%. Factors significantly associated with proteinuria were : the gender ; CD4 count &lt;350/mm3 ; viral load &gt; 100000copies/mm3 ; BMI &lt; 18.5kg/m2 ; Hemoglobin level &lt; 8.5 g/dl, chemoprophylaxis with Cotrimoxazole and WHO clinical stage 3 and 4. The frequency of nephropathy during HIV infection in infectious diseases ward of Fann in Dakar suggest to include screening with urinary strip in the initial and follow up checking of all patient infected by HIV. And in all cases favoring factors of this nephropathy should be corrected. Kidney biopsy could help for better studies.

Long-term follow-up of HIV seroconverters in microbicide trials – rationale, study design, and challenges in MTN-015

Background: As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort.Methods: Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing.Results: MTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness.Conclusions: Enrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women.

Non-human primates in HIV research: Achievements, limits and alternatives

An ideal model for HIV-1 research is still unavailable. However, infection of non-human primates (NHP), such as macaques, with Simian Immunodeficiency Virus (SIV) recapitulates most virological, immunological and clinical hallmarks of HIV infection in humans. It has become the most suitable model to study the mechanisms of transmission and physiopathology of HIV/AIDS. On the other hand, natural hosts of SIV, such as African green monkeys and sooty mangabeys that when infected do not progress to AIDS, represent an excellent model to elucidate the mechanisms involved in the capacity of controlling inflammation and disease progression. The use of NHP-SIV models has indeed enriched our knowledge in the fields of: i) viral transmission and viral reservoirs, ii) early immune responses, iii) host cell-virus interactions in tissues, iv) AIDS pathogenesis, v) virulence factors, vi) prevention and vii) drug development. The possibility to control many variables during experimental SIV infection, together with the resemblance between SIV and HIV infections, make the NHP model the most appropriate, so far, for HIV/AIDS research. Nonetheless, some limitations in using these models have to be considered. Alternative models for HIV/AIDS research, such as humanized mice and recombinant forms of HIV-SIV viruses (SHIV) for NHP infection, have been developed. The improvement of SHIV viruses that mimic even better the natural history of HIV infection and of humanized mice that develop a greater variety of human immune cell lineages, is ongoing. None of these models is perfect, but they allow contributing to the progress in managing or preventing HIV infection.