Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP. Plans and preparations for implementing HIV prevention strategies using antiretrovirals (ARVs) are being debated internationally. Evidence of efficacy of oral tenofovir disoproxil fumarate (TDF) and coformulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as pre-exposure prophylaxis (PrEP) has been demonstrated for HIV-uninfected individuals –4 and apHIV serodiscordant couples represent the priority population for implementation of ARV-based HIV prevention in Africa. Half of HIV-infected persons in marital or cohabiting relationships have partners who are not infected –26. RateInternational scale-up of antiretroviral therapy (ART) for treatment of HIV-infection is considered a resounding public health success –36. The Effectiveness of PrEP depends largely on adherence, as indicated by the association between drug levels as an objective adherence measure and efficacy in the four PrEP trials in which efficacy has been demonstrated –4, 38–45Excellent adherence to ARVs as HIV treatment in Africa reflects a number of contributing factors. Great emphasis has been placed on adherence as part of routine clinical follow-up care. Many clinics have professional staff  dedicated solely to providing adherence education and support. Clinics have also drawn liberally upon non-professional, community-based resources to support patients’ ART adherence efforts. For example, having a treatment partner is a condition of starting ART in many treatment programs. Treatment partners are laypersons who are charged with helping HIV-infected persons on ART adhere to daily dosing. A number of experimental studies have now documented the impact of treatment partners on ART adherence rates –62 and c“Peers” (“persons living with HIV/AIDS”) are also increasingly being recognized in Africa as a non-professional resource with important contributions to make to adherence. The roles of peers have steadily expanded from education and support to include activities of care. As ART scale-up took hold, peers were relied upon first to provide emotional support and “positive role modeling”—helping patients to accept an HIV diagnosis and “live well” with HIV/AIDS –65. OverWhether excellent ARV adherence will be achieved in the prevention context—where the perceived need for “medicine” may be less urgent and the concept of “drugs for prevention” less familiar—is an important and very real question. The importance of adherence underscores the need to understand how individuals will cope with taking ARVs to prevent HIV infection, and how their efforts to adhere can best be supported.The adherence successes of ART scale-up in Africa contain important lessons for replicating these successes as ARVs become available for use in prevention. One such lesson is that family members, friends and peers of persons taking ARVs are both interested in and capable of effective adherence support for HIV treatment. Understanding this, it makes sense to ask whether similar resources may be available in the prevention context. We begin to address this question by characterizing social influences on adherence observed in the Partners PrEP Study, a randomized clinical trial of daily oral PrEP for HIV prevention among HIV serodiscordant couples in East Africa.This study was approved by the Partners Health Care Human Research Committee, Boston, MA; the Human Subjects Division of the University of Washington, Seattle, WA; and the Uganda Council on Science and Technology, Kampala, Uganda. Written consent was obtained from all participants.This analysis is based on data collected through in-depth qualitative interviews with 88 adults who were HIV-uninfected partners in Ugandan HIV-serodiscordant couples. Qualitative interviewees were part of an ancillary adherence substudy  that useA purposeful sampling strategy was used to identify qualitative study participants. Purposeful sampling lays the groundwork for in-depth qualitative analysis by systematically representing a variety of perspectives on an object of study . “Low” aRecruitment for the qualitative study took place over 27 months, from April 2010 to July 2012. Efficacy of PrEP for HIV prevention was demonstrated and the Partners PrEP Study unblinded in July, 2011, meaning that participants entering the qualitative study after that time had been informed they were receiving PrEP (rather than placebo) and that PrEP was efficacious . The intQualitative interviews were carried out by Ugandan research assistants (RAs) trained in qualitative research methodology. They took place in private locations—in patients’ homes, at the research offices, or near the clinic—where conversations could not be overheard. Conversations were audio-recorded with permission and typically lasted about an hour. A qualitative interview guide was used to address the following topics with each participant: (1) experiences of taking study pills, (2) descriptions and explanations of particular missed doses, (3) accounts of adherence lapses (when more than a single dose was missed), (4) strategies for sustaining adherence, and (5) impact of serodiscordance on the partnered relationship. Neutral probes were used to elaborate responses and elicit illustrative examples. Following each interview, RAs generated a complete transcript in English from local language audio recordings. Transcripts were reviewed for quality . The transcripts constitute the qualitative data analyzed for this report.The starting point for this qualitative analysis was the explanation of PrEP adherence arrived at through our initial examination of these data, in which we identified the desire to preserve the partnered relationship as an important social motive for adherence to study product or placebo by HIV-uninfected individuals in the Partners PrEP Study . Our goaThe first and second authors reviewed the data for content illuminating the roles or potential roles of laypersons in PrEP adherence . The relIn addition to the qualitative analysis, we compiled descriptive quantitative data on personal characteristics of the 88 qualitative participants and summarized rates of adherence.Results of analyses are presented in the following order. Quantitative data reporting personal characteristics and adherence rates of the sample appear first, as background. These are followed by categories describing lay social resources for adherence support, the primary focus of this analysis.Forty-eight men (54.5 %) and 40 women (45.5 %) made up the qualitative study sample. Median age for the group was 34.5 years (IQR 29.8–39.3 years). All participants described themselves as married and living with their partners at the time of enrollment. “Marriage,” as the term is used locally, refers to unions that may or may not have been sanctioned by a religious or civil authority. Median duration of the partnered relationship was 7.6 years (IQR 4.1–16.2 years). Most (84.1 %) participants had children with their partners; median number of children was 2. Median adherence was 90 % (IQR 83.7–95.5 %) for low adherers and 100 % (IQR 99.6–100.3 %) for perfect adherers by UPC for the duration of their participation in the ancillary adherence substudy.Qualitative analysis identified a number of potential lay social resources for support of PrEP adherence. These are detailed below under the headings: (1) The partnered relationship as adherence support, (2) Adherence as a “Family Affair,” and (3) Relationship support as adherence support for serodiscordant couples.Interviewer: “How does your partner assist you in swallowing your medicine?”Respondent: “Well, there are times when she reminds me. We can be there conversing and then she checks on the clock and tells me that it’s time for medicine. Then, she brings it to me and I swallow.”Relationship partners provided direct adherence support for HIV-uninfected individuals taking study product or placebo. Support ranged from simple encouragement to “keep taking your pills,” to presenting pills and accompanying water and/or food for easy dosing at the scheduled time, to running after a departing spouse with a forgotten pill bottle in hand. Often, support involved sharing adherence responsibility by offering reminders at dosing times. Couples in which the HIV-infected partner was also taking ART or cotrimoxazole as prophylaxis often took their pills together. The following examples from interview transcripts illustrate the ways in which partners provided adherence support:Interviewer: “How did you then decide to resume taking the drugs?”Respondent: “When I came back home, I started again taking my drugs. This was after asking my husband what I should do, because I had feared the drugs. He tried to explain to me because for him he understood better what we had been told at the clinic. He assured me that the drugs had no problem and encouraged me to resume and I did so.”Male, Low Adherer, Age 19He [husband] really helps me a lot. ….He tries to remind me and he keeps encouraging me to swallow my medicine well. He tells me never to miss even for a day. If he suspects I don’t have money for transport [to clinical follow-up visits] he will meet me on the way [to the clinic] and give it to me. I have never lacked transport, not even for a single day. If he doesn’t have money, he will borrow from friends at work and bring it to me.Female, Low Adherer, Age 29Interviewer: “How does your partner help you in swallowing your drugs?”Respondent: “She helps me a lot and I also help her a lot because every night she is also swallowing her drugs.”Interviewer: “How does she help you?”Respondent: “The way she helps me [is], we agreed on the time when we should be having supper, and we also agreed that by the time everyone swallows their drugs, they should have eaten supper first. So for us by 8.20 p.m. we are always through with supper. After supper, we reach for our drugs and swallow them.”Female, Perfect Adherer, Age 27Male, Perfect Adherer, Age 44Interviewer: “How do you remember to take your pills?”Respondent: “I told my child. When it clocks 7:00 p.m., he comes and tells me to swallow my medicine.”Interviewer: “How old is he?”Respondent: “He is six years.”Interviewer: “How does he tell the time?”Respondent: “I told him that I am supposed to swallow this medicine at 7:00 p.m., so he should remind me in case I forget. We don’t have a watch but he is able to somehow tell that it’s time. I have a radio, but I never have time for it. I don’t have a phone. It’s my son who reminds me.”Partners were not the only family members providing adherence support. Children were also actively involved. Interviewee reports consistently depicted children as eager to contribute and conscientious in reminding their parents to take their pills at dosing times. Even young children proved themselves to be reliable “reminders”:Interviewer: “Besides the phone and the radio; what else reminds you to swallow your medicine?”Respondent: “My children. When it’s time, they tell me ‘Mum, its time.’”Interviewer: “How did your children know that you swallow medicine?”Respondent: “I explained to them. I told those who are older; I told them the truth and showed them the pills. That time, I had not yet bought a phone; so, they would remind me always. They have a name for my medicine; they call it ‘ground nuts [a peanut common in the region].’ So, they always say that, ‘Mum, it’s time to swallow your ground nuts.’ Even if the radio is off and maybe my phone has no battery, they will come and ask ‘Mum, don’t you think it’s time for your ground nuts?’”Female, Perfect Adherer, Age 34Female, Perfect Adherer, Age 42It’s not common to forget [a dose], because when I got this medicine, I reached home and showed it to everyone, including the children, and told them the time I am supposed to swallow it. Even when I am at my mother-in-law’s place, you find her asking me whether I remembered to swallow the medicine. Even the children remind me. And when my husband is around, he also reminds me. This is what has helped me swallow my medicine well. Because when you keep it a secret and you hide it from other people, you will forget and there won’t be anybody to remind you. It’s important that other people are in the know so they can remind you.Children typically become involved in adherence when asked to do so by a parent, as in the examples above. Help can also be requested from other family members to create a family network of adherence support. Creating a family adherence support network presupposes disclosure of HIV-positive status but changes its meaning. Rather than a threat, disclosure for activation of family support becomes a means to a desired end. Making adherence into “a family affair” through disclosure is a culturally congruent adherence strategy that makes effective use of available social resources. One woman described how she accomplished this:Female, Low Adherer, Age 30When [I saw] that he [husband] was infected with HIV, I spent several months without having sex with him. I packed my bags and went to my parents’ home. I spent three months there. Then some elderly man in my husband’s neighborhood came and picked me to go back to him. I accepted. But when I reached there, he again wanted me to have sex with him. I refused totally and packed my bags again and went back to my parents. This time his brothers on his paternal uncle’s side came. They asked him the reason why we were separating. Then they concluded that since I was the only known wife, I should be left to be at home and raise my children but he gives me my peace. That is when I again went back to him. They asked him whether he agreed with the decision and he accepted. So I went back.Authors of a recent ethnographic analysis explaining why marriage and childbearing, as life priorities, may interfere with HIV treatment in a West African society characterized marital relationships as “collective projects in which families and communities are highly invested” . In dailI was going through his things and found some medicine and his medical forms. I asked him to explain what they were. He instead quarreled, asking why I went through his things without his knowledge. I decided to go home to my parents. He didn’t want me to leave but I insisted. [Later] he followed me to my home. My parents were present. I told them the reason I left was because I found my husband with pills in his bag and he told me he is HIV-positive. I told them I didn’t want to go back to his home. My parents gave us advice. They said, ‘haven’t you seen people who are positive and are living together?’ They told us to go to the hospital and seek guidance from health workers. Since the time we joined the study, we have not quarreled at all.Female, Low Adherer, Age 39Female, Perfect Adherer, Age 27After some time, I told him, ‘if you do not want to test with me, remain alone and I also will remain alone.’ We separated. Good enough. The person who tested me is my friend, and he started advising me. …He insisted if we both went to him, he would teach us how to use a condom. Then my husband said, ‘I cannot use a condom on my wife.’ I told him I cannot accept unprotected sex. I said, ‘if this is [how it is], let us remain separate.’ So we separated our beds. Then, because we are legally married, he went and reported me to church leaders. They sat us down and talked to us about our issues. Later we went to [health center in a nearby town]. They also educated him. They told him if he does not accept, he should allow me to go back to my parents’ home. That is when he accepted and started using condoms. From that time we reconciled and became one.In addition to family, friends and neighbors, the interviews point to other existing resources in local communities available for relationship support. These include a range of formal organizations , as well as individuals seen as community leaders . Couples do not hesitate to draw on these resources in working to resolve threats to their relationship.Respondent: “He [husband] has said that the very few times I agree to have sex with him do not satisfy him. But if he was using condoms very well, I wouldn’t be having any problem. When we have sex [infrequently], they have not broken. But when the frequency of sex increases, the condoms break. …Sometimes we spend a week apart because he has chased me from home [over this]. I spend nights at different people’s homes.”Interviewer: “How helpful have these people been in resolving your disagreements?” Respondent: “They try to arbitrate but we disagree afresh. Actually, there is no place we haven’t been to [to seek help]. We started by going to the counselors at TASO . We went to the probation office at the district. We went to the police. It is only the family members who have not met. This is the remaining option.”Female, Perfect Adherer, Age 48Interviewer: “How did your discordant status affect how you get along with your husband in the relationship?Respondent: “He first wanted to always sleep with me without a condom. We feuded over this and I ended up separating from him and went back to my parents for some time. He followed me home and I disclosed to my parents what the issue was. They called a meeting of counselors and elders in the village, who gave him advice. He heeded their advice, and we agreed to use condom, which I always get from the health center, nearby.”Female, Low Adherer, Age 29Female, Perfect Adherer, Age 36indirect resources for support of adherence already existing in communities.Our qualitative data point to relationship partners as direct sources of adherence support to HIV-uninfected individuals taking PrEP or placebo as part of this study. If partners provide direct support, then efforts to help serodiscordant couples repair their relationships and live together without discord represent Good adherence will be central to success in using ARVs to prevent HIV transmission and curb the epidemic. Adherence is enhanced through consistent adherence support. In Africa, professional resources for providing such support may be scarce, but informal, lay resources are likely to be both plentiful and effective. Through qualitative data, this paper offers a glimpse of what family and community-based support for PrEP adherence from spouses, other family members, and the larger community might look like for African serodiscordant couples who choose to disclose their serodiscordant status.This paper documents the availability of social resources to support couples in adherence to ARV-based prevention. The next step will be to develop strategies and systems for deploying these resources. At least two general approaches present themselves to start. Ways of integrating laypersons into activities of clinical care—working alongside professionals in clinics as educators or counselors—need to be identified. At the same time, these resources can serve as building blocks for the construction of a community-based network that might support adherence, facilitate disclosure, combat stigma, help couples negotiate relationship problems, and educate the public about the use of ARVs for prevention. Existing community-based support organizations in which HIV-affected families are already active or have a stake might provide good starting points. Examples include church-sponsored couples’ education and support groups, civic groups active in supporting HIV-prevention activities (e.g. testing), and/or groups organized for economic self-help.ART is a lifetime commitment, but use of PrEP by African serodiscordant couples will likely be time-limited. In East and West African Demonstration Projects, couples are being offered PrEP as a “bridge” to initiation of ART , 79. In Adherence to PrEP may be more variable and more challenging than adherence to antiretroviral treatment, as the motivating effect of dramatic health gains after starting ART will be lacking. Data on PrEP adherence in demonstration projects are just beginning to appear. An early report on adherence to daily oral PrEP by HIV-uninfected partners in serodiscordant couples taking part in the Partners Demonstration Project in Kenya and Uganda shows both high adherence and frequent  gaps and  breaks . UnderstPurposeful sampling intentionally represents varying perspectives on a topic of study through the inclusion of participant groups with contrasting experiences. In this sample, varying perspectives are represented through inclusion of low and perfect adherers. The sample was not constructed to identify differences among constituent subgroups; thus our analysis of group differences is limited. Qualitatively, we determined generally that identified categories of adherence support applied to both low and perfect adherers. Illustrative examples from both groups are included in the descriptions of each category as confirmation of this.We have argued here for the importance of partners as sources of adherence support. Accordingly, discord in the relationship can detract from adherence success. A partner leaving home in anger after an argument may forget to take pills along. Tension and fighting with a spouse can undermine adherence motivation when typically the very reason for accepting ARVs is to preserve the relationship. Adherence support provided by a partner and/or by being in a partnered relationship is likely enhanced when the relationship is stable.Relationship Support as Adherence Support category, could not be fully developed.The following limitations of this analysis should be pointed out. The data were collected in a research setting in which adherence was both investigated and consistently reinforced. This may have resulted in greater involvement in adherence by family members and friends than might be typical outside the context of research. At the same time, the qualitative study was not designed and did not set out to elicit data on lay social resources for adherence support. The clear evidence of social involvement in adherence that emerged from the interview data suggests both that the phenomenon is real and that more could have been learned about a broader array of sources of support in the community, had this been a study focus. Nevertheless, the lack of initial focus on lay social resources for adherence support means some categories, notably the Data for this qualitative study were collected at a single site in one country only, limiting generalizability. Most qualitative research, this study included, does not aim for generalizability but rather at the delineation and interpretation of concepts. Qualitatively, limiting data collection to a single site in a single country means variation across communities and/or cultural settings cannot be addressed.Effectiveness of ARVs for prevention of HIV transmission depends on adherence success. Support from professionals, peers, family members and friends has been central to the excellent adherence achieved by individuals in Africa taking ART for HIV treatment.ART scale-up has brought increasing involvement of laypersons in activities of care as a means of alleviating health care personnel shortages. Now, with evidence of the efficacy of TDF and FTC/TDF as PrEP, pressures on overburdened health systems will once again intensify. As PrEP is implemented in demonstration projects and routine health care settings, it is important to identify acceptable and effective strategies to optimize adherence and reduce burden on clinic staff. These qualitative data suggest laypersons—family members, peers, members of the larger community—constitute a promising resource for PrEP adherence support that merits further investigation.


Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF.This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy.Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5–7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5–721.5] and 62 copies/mL , respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr .Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients. Chronic kidney disease in persons infected with HIV is an important part of the changing epidemiology of the disease. Prior to the introduction of combined antiretroviral therapy (cART), HIV-associated nephropathy (HIVAN) was the most common cause of kidney disease in HIV.  However,However, TDF can be associated with renal dysfunction. Reports of tubular damage, Fanconi syndrome, interstitial nephritis or overall decrease in estimated glomerular filtration rate (eGFR) have been associated with its use. , 6–8 TheRats exposed to high doses of TDF have been shown to develop renal cortical damage with glomerular and proximal tubule distortion.  TDF may Certain factors may exacerbate the nephrotoxic effect of TDF. In rat models, vitamin D deficiency in TDF-treated subjects has been demonstrated to worsen proteinuria, increase oxidative stress, and contribute to metabolic syndrome and hypertension .  FurthermStudies have demonstrated that the incidence of TDF-induced nephrotoxicity  increases in patients with advanced age, low body weight, increased baseline serum creatinine, advanced HIV (defined as CD4+ T cell count <200 cells/μL), and other comorbidities such as hypertension, diabetes and cardiovascular disease. , 15–18 HConversely, some studies have demonstrated that long-term TDF use did not induce nephrotoxicity, and stilHowever, other professional societies differ in terms of recommendations. For example, the 2014 DHHS guidelines recommend a urinalysis every 6 months if on TDF. The 2010Proteinuria is one marker of renal disease and can be assessed in different ways. The urine protein-creatinine ratio is used by most institutions to approximate the 24-hour protein excretion; however, limitations include fluctuations in urine creatinine concentrations at various times of day as well as different patterns of excretion of urine protein and creatinine (and therefore variable protein-creatinine ratios) depending on the type of kidney injury.  The P/O-The objective of our study was to define the prevalence of abnormal urine P/O-ratio and subsequently determine whether the urine P/O-ratio associates with abnormal estimated GFR in patients receiving TDF therapy as a component of cART. Additionally, we aimed to identify risk factors for renal dysfunction in this population.Human subjects were involved indirectly through retrospective chart review. All subjects had previously signed releases of information authorizing their charts to be reviewed for medical research purposes before the study was conducted. All records reviewed were kept confidential, and patient-identifiable information was de-identified prior to analysis. The minimal risk, HIPAA-waiver study received approval from the Mayo Clinic Institutional Review Board (IRB#13–003409).This was a retrospective, single-center, cross-sectional chart review study involving patients seen in the HIV clinic at Mayo Clinic, Rochester, MN. The patients served by this clinic include those living in Olmsted County and surrounding counties, as well as many who travel from their hometowns throughout the US and the rest of the world to seek HIV care in Rochester. Medical records of patients within the Mayo Clinic HIV Database from January 1, 2010 to December 31, 2013 were reviewed for eligible subjects.Subjects were included in the study if they met the following criteria: (1) adults ≥18 years old, (2) diagnosed with HIV-1 infection, (3) were on a TDF-containing cART regimen between January 1, 2010 and December 31, 2013, and (4) had at least one documented urinalysis and two serum creatinine levels within the study period. Subjects were excluded from consideration if they (1) were less than 18 years old, (2) had a previous diagnosis of chronic kidney disease or proteinuria identified prior to the study period, regardless of TDF use (3) had documented receipt of additional potentially nephrotoxic medications during the period of abnormal urinalysis or renal insufficiency, or (4) had no documented urinalysis between January 1, 2010 and December 31, 2013.Demographic and clinical characteristics, P/O-ratios, serum creatinine, eGFR, and comorbidities , were collected using a standardized case report form. All TDF-monitoring P/O-ratios obtained during the study period were included. The first abnormal P/O-ratio encountered was used to determine the prevalence of abnormal P/O-ratio among subjects on TDF between 2010 and 2013. The date of the last urinalysis between 2010 and 2013 was used in the calculation of duration of TDF therapy for all study subjects. Additional information collected included concurrent use of non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) or integrase inhibitors, hepatitis B and C co-infection status, presence of concomitant nephrotoxic medications , presence of concomitant renoprotective medications (ACE inhibitors and angiotensin receptor blockers), CD4+ T-cell count at beginning of study period, and HIV viral load > 100,000 copies/ml at beginning of the study period.2 on two separate readings at least 3 months apart and/or persistent proteinuria. [Chronic kidney disease is defined as a functional or structural kidney abnormality present for ≥3 months, with diagnostic criteria including eGFR  equation) <60 mL/min/1.73 meinuria.  The P/O-The normal P/O-ratio was defined as ≤0.12, which corresponds to a normal protein-creatinine ratio of ≤0.05 . Predict2. The eGFR was calculated using the National Kidney Foundation endorsed four variable MDRD equation as follows: [In this study, we classified predicted 24-hr proteinuria as normal/mild (<150mg/24hrs), moderate (150-500mg/24hrs) or severe (>500mg/24hrs), according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Abnormafollows: eGFR  an annual basis for subjects on TDF-containing regimens, according to 2009 DHHS guidelines (which were the most current at the start of the time period being investigated).  Any otheStatistical analyses were performed using JMP software version 10.0 .Descriptive statistics were used to describe baseline clinical characteristics of the subjects. Factors associated with abnormal P/O ratio, or abnormal eGFR during TDF therapy were determined using a univariate logistic regression analysis with Chi-squared and Fisher’s exact test as appropriate to calculate odds ratios with 95% confidence intervals. Factors with significant odds of association with abnormal P/O ratio or abnormal eGFR were included in a multivariable logistic regression analysis. P values were calculated with likelihood ratios and values <0.05 were considered statistically significant. Sensitivity analyses were performed where appropriate to exclude potential confounding factors.Characteristics of the 117 subjects included in the study are listed in 2 respectively. After adjusting for age, subjects on TDF >5 years had almost a four-fold increased association with an abnormal P/O-ratio than people on TDF for <1yr . When a sensitivity analysis was performed excluding diabetic subjects and treating duration of tenofovir use as a continuous variable, there was a difference in association with abnormal P/O-ratio per 1 year increment on tenofovir . A 10-year increase in age above the mean was associated with having an abnormal P/O-ratio  and abnormal GFR .Tables All 11 diabetic subjects had an abnormal P/O-ratio. Subjects with hypertension were more likely to have abnormal eGFR . When a sensitivity analysis was performed, excluding diabetic subjects did not have a significant impact on the association of abnormal eGFR and age or hypertension, nor did it have an impact on the association of abnormal P/O-ratio and duration of TDF >5 years. However, exclusion of diabetics eliminated the significant association between abnormal P/O-ratio and age . The sensitivity analysis also eliminated the trend to significance between abnormal P/O-ratio and hypertension . Abnormal P/O-ratio was not significantly associated with abnormal eGFR in this cross-sectional study (p = 0.17), suggesting that in order to adequately monitor renal function in TDF treated patients, both functional markers (e.g. eGFR) and proteinuria assessments are needed.Increasing age was significantly associated with abnormal renal function on TDF as determined by P/O-ratio and eGFR, which corresponds with findings from previous studies that TDF-containing regimens should be used with caution in older subjects or those with diabetes., 15. ThiAlthough the results of our study do not indicate that an elevated P/O-ratio is associated with a high prevalence of low eGFR in HIV infected patients on TDF, the association of TDF duration and renal abnormalities can also be viewed as a confounder of duration of HIV infection. Patients who have had HIV for more years, especially those with viremia, were more likely to have underlying HIVAN, and in these situations, it would be difficult to identify whether or not renal dysfunction in these patients was secondary to HIVAN or antiretrovirals. It should be noted that our study was cross sectional and follow up was limited. The presence of an abnormal P/O could be an early presentation of chronic renal damage that would result in decreasing GFR with prolonged therapy. More studies are needed to better identify the cause of kidney diseases and their natural history in patients treated with TDF.In addition, more studies are needed to identify the best laboratory monitoring for renal dysfunction in patients on TDF. In a retrospective cohort study done on 356 HIV-infected patients in Thailand, TDF-associated renal dysfunction was assessed using 3 different methods: serum creatinine (SCr), calculated creatinine clearance (CCrCl), and eGFR. Significant change of SCr was detected in 5.3% of patients, in contrast to CCrCl (14.9%) and eGFR (17.7%). The investigators concluded that SCr is less sensitive than CCrCl and eGFR for detecting renal function decline in their cohort. This was likely because endogenous creatinine production is determined by muscle mass and dietary intake, which varies among different ethnic and age groups. In addition, a significant increase in SCr is detected only when GFR decreases to 60% of normal.[The 24-hour urine collection is the standard method of quantifying proteinuria, although spot protein can be used to approximate the 24-hour proteinuria, as it is often difficult to obtain 24-hour protein collections in the outpatient setting. Spot protein is recommended for initial screening purposes with a 24 hour urine collection for confirmation. Furthermore, routine 24-hour urine collections are performed so infrequently clinical practice that few patients can be studied using this parameter in a retrospective study. Albumin/creatinine ratio and protein/creatinine ratio are alternative parameters that can be measured, but these are not routinely performed in our HIV clinic. Additionally, limitations associated with quantitative analyses include the variable fluctuations in urine protein, including hydration status, physical activity or illness, and menstrual blood, vaginal discharge or semen in the urine sample.  On the oTubular dysfunction may exist in the absence of detectable glomerular dysfunction. TDF is eliminated in the urine by both glomerular filtration and proximal tubular secretion, so damage at either the glomerular or tubular level is significant. In a prospective observational study in Spain, 284 HIV patients were examined: 154 on TDF, 49 on other HAART regimens, and 81 drug-naïve. This study assessed both glomerular and tubular parameters of kidney function in HIV individuals. Glomerular parameters included plasma creatinine levels and creatinine clearance. Tubular parameters included glucosuria, hyperaminoaciduria, hyperphosphaturia, hyperuricosuria and beta-2-microglobulinuria. Although the 3 patient groups had no significant differences in glomerular parameters, up to 22% of HIV patients treated with TDF showed two or more abnormal tubular parameters. In contrast, this observation was found in only 6% of patients treated with other HAART regimens and in 12% of antiretroviral-naïve patients.Chronic tubulopathy in the absence of glomerular dysfunction is clinically relevant because a subset of patients may progress to renal insufficiency over time. In addition, long-term consequences of chronic hyperphosphaturia (a marker of tubular dysfunction) may lead to premature osteoporosis. Moreover, beta-2–microglobulin concentrations in urine are a sensitive marker of tubular damage. In the previously mentioned study, patients on TDF showed the greatest levels of beta-2–microglobulin in urine, which reinforces the potential for tubular toxicity of TDF. Some authors have proposed monitoring urine beta-2–microglobulin in patients on TDF to identify those at increased risk for renal injury. Still otHowever, current DHHS guidelines have not included tubular parameter monitoring as part of their recommended guidelines for routine TDF monitoring. As a result, it is likely that these tests are underutilized by clinics that follow the DHHS guidelines for antiretroviral management. For example, our HIV clinic routinely performs screening urinalysis which includes a measure of proteinuria (P/O-ratio) but does not routinely request measures of tubular damage according to practice guidelines. Based on the results of this study, it is reasonable for HIV clinics to consider including more formal evaluation of tubular damage in routine monitoring urinalyses for patients on TDF.Given ongoing concerns regarding potential nephrotoxicity of TDF and the need for continued nucleotide reverse transcription inhibitors in the backbone of cART regimens, tenofovir alafenamide fumarate (TAF), a new TFV prodrug, was recently FDA approved. TAF has been shown in clinical trials to be associated with fewer renal adverse effects compared to TDF. –41 HowevThe retrospective nature and small sample size of this study limit the ability to make accurate predictions regarding the associations of P/O-ratio and abnormal renal function. Many of the patients in our clinic come to us already on TDF-containing cART regimens; therefore identifying a control cohort not on a TDF-containing regimen was difficult, which was a limitation of the study. Additionally, baseline urinalyses to capture P/O-ratio prior to initiation of TDF were not available for every patient to determine a true incidence or time to event analysis of renal dysfunction as measured by P/O-ratios or eGFR. It would have been ideal to validate our P/O-ratio findings by comparing to protein-creatinine or 24hr proteinuria collection. However, this is difficult to achieve in a retrospective study if not part of routine practice. Nevertheless, future studies would certainly include a prospective analysis, identifying both glomerular and tubular measures of renal disease. Despite these limitations, the associations identified between duration of TDF therapy and P/O-ratio have important implications for patient care.Our study demonstrated that abnormal renal function, as measured by abnormal P/O-ratio, was common in HIV infected patients on TDF but was not associated with abnormal eGFR, suggesting that it may be a very early biomarker of decreased renal function in HIV infected patients. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in these patients; therefore, caution should be used when prescribing this medication in older patients or patients with hypertension or diabetes. Newer antiretrovirals provide an opportunity for alternative regimens with a tenofovir backbone; however these are likely to be out of reach to resource-poor communities. Therefore, because patients worldwide will likely still be on TDF-containing regimens, our study and future studies of TDF remain relevant to identify optimal parameters with which to monitor renal function in HIV patients, which could include both glomerular and tubular surrogates.


To investigate the reasons and risk factors for modification of the first combined antiretroviral therapy (cART) currently used for HIV infected patients who were treatment naïve in Shanghai China.Making a retrospective observational research on treatment naïve patients with HIV infection who initiated cART during the period of September 1st 2005---December 1st 2013. The demographic and clinical data were collected from the first visit to the time of the first regimen modification or the last visit in December 1st, 2014. The reasons of treatment modification were recorded. Survival analysis of modification was made by Kaplan-Meier curves analysis and log rank test, and a Cox multiple regression model was constructed to identify related factors of modification.P = 0.010), CD4 less than 200 and the initial regimen they received. Compared with the regimen of TDF+3TC+EFV, patients with regimen of d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial regimen, respectively.A total number of the eligible participants were 3372 and 871(25.8%) patients changed their first cART regimen. The median follow up was 22 months [interquartile range (IQR) 14–39]. Among patients who modified the original regimen, drug toxicity occurred in 805(92.4%) participants and 44(5.1%) experienced treatment failure. In multiple regression analysis regimen modification was associated with patients’ age more than 40 years old (aHR 1.224, 95%CI 1.051–1.426, The main reason for the regimen switch was drug toxicity and main risk factors for regimen modification were age older than 40 years, CD4 cell counts less than 200 at baseline and regimen they received. Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the highest risk for modification while the regimen of TDF+3TC+EFV was the most tolerable treatment regimen in first years’ follow up. There has been a rapid and successful scaling-up of combined antiretroviral therapy (cART) in China and the other parts of the world over the past decade –5. SinceAs for Shanghai in China, with the continual introduction of new antiretroviral treatment medications, such as LPV/r and TDF, the clinicians have more choice to implement the cART with more effective and less toxic medications. However there were still a number of HIV infected patients could not endure the treatment and switch the first regimen. In this paper, we evaluated the reasons for the modification of first cART in a large cohort of HIV-1 infected patients from Shanghai, China. We also analyzed the risk factors for modification. The findings of this study will provide valuable information for the first regimen selecting and visit plan making for treatment naïve patient in the future.This research protocols received ethical approval from the Shanghai Public Health Clinical Center Ethics Committee. The committee decided to waive the need for written informed consent from the participants studied in this analysis as the data were analyzed retrospectively and anonymously..For patients who initiated cART during the period of September 1st 2005—-December 1st 2013 were selected retrospectively for this survey according to the following criteria: HIV-1 positive, aged more than 16 years old, antiretroviral treatment naive, cART comprising 2 nucleoside reverse transcriptase inhibitors (NRTI) and 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Follow up was continued until December 1st, 2014. Patients’ characteristics recorded at baseline included age, gender, marital status, HIV exposure route, initial cART regimen and CD4 cell counts. The WHO stage was assessed by the clinicians in the first visit in clinic. Antiretroviral therapy regimens were categorized as: zidovudine (AZT) and lamivudine (3TC) with either lopinavir/ritonavir (LPV/r) or efavirenz (EFV)/neviripine (NVP); d4T and 3TC with either LPV/r or EFV/NVP; tenofovir disoproxil fumarate (TDF) and 3TC with either LPV/r or NVP/EFV; and other regimen (TDF+ emtricitabine (FTC)+EFV). A small number of patients were excluded because their first regimen included the drug of IDV (indinavir), DDI(didanosine) or TMC(rilpivirine). Patients who dropped out or died in the follow-up or did not make CD4 test or WHO stage assessment were also excluded. The modification of cART regimen was defined as a change of at least one antiretroviral drug of the first regimen. For each patient, we calculated the time from the initiation of cART regimen to the switch. In the absence of these changes, follow-up ended at the last visit on December 1st 2014. The main reasons for treatment modification were classified as toxic effects, treatment failure, and other reasons(containing patient’s wish and co-infection). The treatment failure was determined by HIV load test and the criteria was in line with the WHO guideline for HIV infection treatment . All of Data analysis was conducted by IBM SPSS version 19.0 . Continuous variables were described using means and standard deviations or median and interquartile range (IQR) while categorical variables were described by percentages. The chi-square test was used for categorical variables and the t-test for continuous variables. We used Kaplan-Meier curves to describe the cumulative incidence of treatment modification of the most frequently used initial antiretroviral regimens, and the curves were compared by log-rank test. Risk factors of treatment modification from the time of starting cART to the last visit on December 1st 2014 were analyzed using Cox proportional hazards models. The model included: patient age at cART initiation, gender, baseline CD4 cell count, WHO stage, type of cART regimen, transmission route and marital status. All hypothesis testing was 2-sided, with a level of α = 0.05.Among 3770 patients who fulfilled the inclusion criteria, there were 398 cases (10.6%) excluded. So in the end, the number of participants in this analysis was 3372. See in . As for From the initiation of cART to the last visit of our research, there were 871 patients switched the first regimen of cART because of drug toxicity, treatment failure and other reasons. Within the first month, 197 patients (5.8%) switched treatment; by 3 months, the number rose to 381 (11.3%), and by 12 months, to 544 (16.1%). Furthermore, the total modification rate was 25.8%. The median follow up was 22 months [interquartile range (IQR) 14–39]. Furthermore, median follow-up time for regimen of AZT+3TC+EFV was 27 months (IQR 17–42); TDF+3TC+EFV was 16 months (IQR 14–20); d4T+3TC+EFV was 24 months (IQR 13.5–40); AZT+3TC+NVP was 23 months (IQR 2–50) and d4T+3TC+NVP was 22 months (IQR 6–43.75).The reasons for regimen modification were showed in . In detaWe divided the participants into two groups, one was patients with regimens modification and the other was patients without modification. The difference of demographic and clinical data between these two groups were analyzed .It showed that the demographic and clinical data such as age, marital status, CD4 cell count and regimens of participants between the two groups were significantly different. In order to analyze which factors played an independent role, we implemented the multiple variants regression by Cox proportional hazards models.The analysis indicated that regimen modification was associated with patients’ age more than 40 years old, CD4 less than 200 and the initial regimen they received. Compared with the regimen of TDF+3TC+EFV, patients with d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial regimen, respectively.Moreover, in the first year after the initiation of cART, patients with different regimen had distinct cumulative modification and this difference was significant (P < 0.0001). It can be seen in . Not onlIn this paper, we made a retrospective analysis on the reasons and risk factors for regimen modification in China which belongs to a limited resource place for HIV treatment currently. Knowing the reasons and risk factors for the modification in China can play a positive role in optimizing the future HIV treatment. In this paper, we excluded the HIV infected patients taking indinavir, didanosine or rilpivirine as the initial regimen for cART. The reason for this exclusion is that these drugs are no longer recommended for treatment due to lack of potency and having more severe toxicities, therefore no new diagnosed patients start cART with these drugs.During the follow-up from 2005 to 2014, totally 29 participants died (0.8%) and 129 patients dropped out (3.7%), this proportion is relatively small comparing with other researches, 20. It Among the patients who switched the first regimen, the total modification rate was 25.8% and the most common reason was drug toxicity. Furthermore, the most frequent toxic effects were lipodystrophy and peripheral neuropathy which were mostly caused by d4T. D4T wasIn our study, the median follow-up time for TDF+3TC+EFV was shorter than other 2NRTI plus 1NNRTI regimens. The main reason for the disparity was that TDF was introduced into China much later than other anti-HIV drugs . Among aAs for the other factors which may influence the modification of the cART regimen, such as baseline CD4 cell count and patient age, we found that patients who had CD4 less than 200/ul had 1.2 times more likely to switch the first regimen than those with CD4 more than 200 and patients who were more than 40 years old had 1.2 times more likely to modified the regimen than those age below 40 years. Both of these were statistically significant. On the one hand, the WHO recommendation indicated that patient’However, our findings should be considered in light of the study limitations. First, this study represents patients from only one center of cART and therefore, may not be generalizable to other clinics. Secondly, as a retrospective study, we can’t make up the data such as baseline HIV load, the CD4 cell count after initiating the cART. Moreover, we are unable to directly assess the outcomes of patients who dropped out and the individual adherence in every visit. However, some of the limitations reflect realities in carrying out such a study in a resource-limited setting.The main reason of modification for the first cART regimen was drug toxicity among patients without cART experience in Shanghai China. The risk factors for initial modifications were patient age older than 40, CD4 cell count less than 200 at baseline and the initial regimen they chose. Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the highest risk for modification while the regimen of TDF+3TC+EFV was the most tolerable treatment regimen in first years’ follow up. With the scaling-up prescription of TDF, the related adverse effects should be monitored.S1 File(XLSX)Click here for additional data file.


To review recent published literature around three areas: long-term nonprogression/viral control; predictors of viral load set point/disease progression; and the potential impact of antiretroviral therapy (ART) in early HIV infection.The natural course of untreated HIV infection varies widely with some HIV-positive individuals able to maintain high CD4 cell counts and/or suppressed viral load in the absence of ART. Although similar, the underlying mechanistic processes leading to long-term nonprogression and viral control are likely to differ. Concerted ongoing research efforts will hopefully identify host factors that are causally related to these phenotypes, thus providing opportunities for the development of novel treatment or preventive strategies. Although there is increasing evidence that initiation of ART during primary infection may prevent the immunological deterioration which would otherwise be seen in untreated HIV infection, recent studies do not address the longer term clinical benefits of ART at this very early stage.A better understanding of the relative influences of viral, host, and environmental factors on the natural course of HIV infection has the potential to identify novel targets for intervention to prevent and treat HIV-infected persons. In the early days of the HIV epidemic, knowledge about the natural history of HIV accrued rapidly. However, the widespread use of effective antiretroviral therapy (ART) brought a shift in focus of the research community away from studies of natural history to those of treated infection. Nevertheless, recent years have seen many advances in our knowledge about natural history. For the purposes of this review, we will focus on three areas of relevance to treating clinicians: long-term nonprogression and viral control; predictors of viral load set point and disease progression; and the potential impact of ART in early HIV infection.The natural course of untreated HIV infection varies widely. The past decade has seen considerable interest in the identification of subgroups of HIV-positive persons who exhibit distinct patterns of disease progression. It is hoped that the information obtained through the identification of such individuals might provide insight for the development of vaccines and novel treatment approaches.et al. identified ART-naive asymptomatic individuals infected with HIV for more than 7 years. Of 312 such patients, only 50 had stable CD4 cell counts, with only 13 having CD4 cell counts consistently in the normal range. Thus, LTNP represented only 0.2% of patients attending for care, a far lower rate than that reported by Okulicz et al., presumably because of the additional requirement that individuals had stable CD4 cell counts.Long-term nonprogressors (LTNP) are individuals who remain asymptomatic for a prolonged period of time off ART with a high CD4 cell count . Altet al.,6▪▪,7,8.▪▪,et al. identifil.[et al.. In a UK10 copies/ml per year over the first 8 years after diagnosis. When the required period of follow-up was increased from 7 to 10 years in a military cohort [▪▪]. As such, it is likely that virtually all HIV-positive persons will eventually experience disease progression if left untreated.LTNP status can be lost, and thus the reported prevalence of LTNP within a study will depend on the required period of follow-up. In Madec's study , LTNP sty cohort , the prey cohort ▪▪. As suet al. identified ART-naive patients who had maintained a viral load less than 2000 copies/ml for more than 12 months. Typical controllers had an average recent CD4 cell count more than 450 cells/μl (2.1% of population), whereas discord controllers had an average recent CD4 cell count less than 450 cells/μl (0.6%). Thus, in this study, the term discord controller was used to identify individuals who had experienced a loss of CD4 cells despite viral control. There were no significant differences in viral load or demographic factors between the two groups. Interestingly, there was a suggestion of a higher frequency of infection with subtype C virus in discord controllers (40% of patients) compared with the entire clinic population of whom 25.1% were infected with subtype C; whether this overrepresentation relates to specific features of subtype C virus itself, or whether subtype C is merely a marker of infection in certain regions of the world with specific host genetic and environmental factors is, however, unclear.More recently, Groves et al.▪▪ identiet al. reported a more marked depletion of the naive T-cell subset in discord controllers than in typical controllers but a trend towards increased activated effector memory CD4 cells in typical controllers. CD8 T-cell activation was increased to a similar level (compared with noncontrollers) in both controller groups. The authors concluded that despite the lower CD4 cell counts in discord controllers, their CD8 T-cell activation pattern more closely resembled that of typical controllers. As with other studies, the discord controllers had higher viral DNA loads than the typical controllers, suggesting continued viral replication in this subgroup.As the two groups of individuals appear to be clinically distinct, suggesting differences in the processes that lead to long-term nonprogression and elite control, several research groups have attempted to investigate whether there are any demographic or biological differences between these two patient groups . Groves et al.▪▪ reportet al. in 141 African seroconverters. In multivariable analysis, higher viral loads in the source partners were associated with higher viral load set points in the seroconverters. The proportion of variation in set point that could be attributed to the viral load of the source partner, after controlling for other factors, was 6%. Despite this low proportion, the authors concluded that the source partner viral load was the most significant predictor of the viral load set point in the seroconverter. Yue et al.[▪▪] also noted the relatively small proportion of variance in the viral load set point that could be explained by the viral load in the source partner. In an analysis of 195 transmission pairs from Zambia, the viral load in source partners explained only around 2% of the variance in viral load set points of seroconverters. Overall, the viral load set point was a function of the source partner viral load, the sex of the seroconverter, the HLA class I alleles of the seroconverter, and the sharing of HLA-I alleles between partners in a transmission pair. Together, these factors accounted for up to 37% of variance in the viral load set point. Roberts et al.. Immediate use of ART reduced the chance of experiencing a CD4 cell count less than 350 cells/μl while the patient remained on ART, but not beyond the duration of treatment. Using data from the observational CASCADE collaboration, Zugna et al.[Several recent publications provide further evidence that initiation of ART during primary infection may prevent the immunological deterioration, which would otherwise be seen in untreated HIV infection. In one observational study, 64% of individuals who initiated ART during primary infection maintained a CD4 cell count more than 900 cells/μl compared with only 34% of those who deferred ART to a later time ▪. In the39na et al.▪ reporteAlthough these studies demonstrate that ART can prevent the deterioration of the immune system which would otherwise be seen without treatment, they do not address whether those initiating ART during primary infection experience any long-term clinical benefit  from this treatment, and thus whether allowing CD4 cell counts to fall to lower levels will result in any appreciable negative consequences over either the shortterm or longterm. Unfortunately, such information can only be obtained from clinical endpoint studies with the requirement for substantially larger sample sizes. The ongoing Strategic Timing of Anti-Retroviral Treatment (START) study  aims to Although the clinical, immunological, and virological course of untreated HIV infection is variable, few persons followed for more than 8–10 years remain without any evidence of disease progression. Variation in viral characteristics, host defence responses (likely explained by variation in host genetics), and environmental factors may all contribute to the variation in the natural course of HIV infection. A better understanding of the relative influence of these factors is emerging. This line of research has the potential to identify novel targets for intervention to prevent and treat HIV-infected persons.None.JDL is a member of the Executive and Scientific Steering Committees for the INSIGHT Network which is currently conducting the START trial. CAS has provided statistical input to various study designs from the INSIGHT group. There are no relevant financial conflicts of interest.▪ of special interest▪▪ of outstanding interestPapers of particular interest, published within the annual period of review, have been highlighted as:Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 353–354).


HIV drug resistance (HIVDR) is the major cause of treatment failure after scaling up of antiretroviral therapy (ART). HIVDR testing prior to ART initiation is not routinely performed in resource-limited settings. We aimed to assess the prevalence of primary HIVDR by short reverse transcriptase (RT) genotypic resistance assay and evaluate of the impact of the mutations on the treatment outcomes.A prospective cohort study was conducted in treatment-naïve HIV-infected patients. Fourteen major mutations of codon 99–191 on the RT gene were selected  at a cost of testing of 35 USD. The association between the presence of primary HIVDR and undetectable HIV RNA (<50 copies/mL) after 6 months of ART was determined.3. The overall prevalence of primary HIVDR was 7.9%. The prevalence of each HIVDR mutation were K103N 6.0%, V106I 1.1%, V108I 0.4%, Y181C 2.3%, Y181I 0.7%, Y181V 0.4%, M184V 3.0%, M184I 1.5%, and G190A 2.3%. No associated factor of having primary HIVDR was determined. By multiple stepwise logistic regression, factors associated with undetectable HIV RNA after 6 months of ART were: having M184V/I , condom use , and adherence per 5% increase .A total of 265 HIV-infected patients were included, with a median age of 35.2  years; 62.6% were males. The median (interquartile range) CD4 cell count at ART initiation was 216 (77–381) cells/mmThe prevalence of primary HIVDR is approximately 8%; it is associated with detectable HIV RNA at 6 months after ART initiation. Routine “short RT” genotypic resistance assay should be considered in resource-limited settings to maximize treatment outcome. In 2001, the Thai government started the National Access to Antiretroviral Program for People Living with HIV/AIDS, which provides antiretroviral therapy (ART) free of charge. Access to ART has dramatically expanded; by the end of 2011, 225,272 people in Thailand had received ART . In spitPrimary HIVDR means that there is resistance of HIV to antiretroviral drugs seen in individuals who have never received ART and who presumably have been infected with a drug-resistant virus –9. PrimaThe potency of ART may be reduced in patients who have acquired a resistant virus. Accordingly, several studies in developed countries have shown a reduction in the efficacy of ART in patients with primary HIVDR compared with patients without primary HIVDR ,18,20,21Currently, HIVDR testing prior to ART initiation is not routinely recommended in resourced-limited countries, including Thailand ,26, due A prospective cohort study was conducted in patients who were diagnosed with HIV infection and who were about to initiate ART from August 2011 to June 2014. Patients from hospitals throughout Thailand were enrolled in the study. Inclusion criteria were patients with a confirmed diagnosis of HIV infection by positive HIV testing according to the Thailand National Guidelines on HIV/AIDS Treatment and Prevention , and who® EasyMAG automatic system . The total RNA was eluted into 55 μL. The reverse transcription–polymerase chain reaction (PCR) of the specific mutation of RT was performed using an Invitrogen SuperScript® RT-PCR System with Platinum Taq DNA Polymerase, with primer pairs HIV-RTF1 (AgACCAgAgCCAACAgCC) and HIV-RTR1 (CTTgCCCAATTTAgTTTTCC). The master mix for RT-PCR contained 25 μL reaction mix (2x), 2.5 μL HIV-RTF1 primer (10 μM), 2.5 μL HIV-RTR1 primer (10 μM), 1 μL RT Taq enzyme, 1.5 μL MgSO4 (50 mM), and 12.5 μL distilled water. A total volume of 45 μL of master mix was mixed with 5 μL of RNA template. Amplification was performed in a thermal cycler. Purification was performed with a MinElute PCR Purification Kit , and then was run on gel (1 kb) for about 1 h. The PCR cleanup process contained PCR product of 5 μL and USB ExoSAP-IT reagent  of 2 μL. The product was then mixed, incubated at 37°C for 15 min, and inactivated at 80°C for 15 min. PCR products corresponding to the RT coding regions were sequenced using an Applied Biosystems 3500 series genetic analyzer (8-capillary array). The master mix for sequencing contained 4.0 μL BigDye® Terminator (v.3.1), 2.0 μL sequencing buffer (5x), 0.5 μL primer (10 mM), 6.5 μL distilled water, and 7.0 μL template. In total, the volume of master mix was 20 μL. The sequencing results were edited using the BioEdit sequence alignment editor and analysis program .A short version of the genotypic resistance assay was designed for detection of codon 99–191 on the RT gene. This region was selected to cover 14 mutations  contributing to NRTI and/or NNRTI resistance. The “short RT” genotypic resistance assay is briefly described as follows. Plasma HIV RNA was purified and extracted using a NucliSENSHIVDR-associated mutations were interpreted to the levels of susceptibility to the RT gene by the Stanford Genotypic Resistance Interpretation Algorithm  from the Stanford University HIV Drug Resistance Database . Medicalt-test and Mann–Whitney U test, as appropriate. The association between the presence of primary HIVDR and undetectable HIV RNA (<50 copies/mL) after 6 months of ART was determined by logistic regression. Variables that presented p <0.10 were considered in a multivariate logistic regression model after assessment of multicollinearity using variance inflation factors. Variables were selected out from a multiple logistic regression model with backward stepwise selection; ones that attained a level of significance were retained in the model. A p <0.05 was considered statistically significant. All statistical analyses were performed using Stata statistical software version 12.0 .Mean with standard deviation (SD), median with interquartile range (IQR), and frequency (%) were used to describe patients’ characteristics. Categorical variables between the two groups were compared using chi-square or Fisher’s exact test, as appropriate. Continuous variables between the two groups were compared using Student’s A total of 265 naïve HIV-infected patients were included; their baseline characteristics are shown in 3, p = 0.010). By univariate logistic regression analysis, only CD4 cell count <200 cells/mm3 at ART initiation was a factor significantly associated with having primary HIVDR . However, no factor was associated with having primary HIVDR, as determined by multivariate logistic regression analysis.The comparison of characteristics between patients with and without primary HIVDR is summarized in 3, p = 0.016) and a lower proportion of HIV RNA <50 copies/mL . By univariate logistic regression, CD4 cell count <200 cells/mm3 at ART initiation , adherence per 5% increase , having primary HIVDR , having M184V/I , having G190S/A , and having Y181C/I  were significantly associated with HIV RNA <50 copies/mL after 6 months of ART (p = 0.013), condom use , and adherence per 5% increase  were associated with HIV RNA <50 copies/mL after 6 months of ART.Fifty-six patients were lost to follow-up after HIV diagnosis and the information regarding ART initiation was missing. A total of 209 patients (78.9%) received ART and were included in the following part of the analysis. The five most common antiretroviral regimens were: tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/efavirenz (EFV), 24.1%; TDF/lamivudine (3TC)/EFV, 20.8%; zidovudine (AZT)/3TC/nevirapine (NVP), 9.4%; AZT/3TC/EFV, 7.6%, and stavudine/3TC/NVP, 6.4%. After 6 months of ART initiation, patients with primary HIVDR had a lower median CD4 cell count  criteria , 28–33. In Thailand, the prevalence of primary HIVDR for NRTI was 0.6–1.9% and for NNRTI 2.8–17% ,17,19,28Only a limited amount of data has been available regarding primary HIVDR and response to ART in resource-limited settings. Multicenter cohort studies have demonstrated that primary HIVDR is associated with poor treatment outcomes and/or clinical complications in developed countries –39. We fThe strength of this study is that it was a multi-center study; patients were enrolled from hospitals countrywide. The prevalence of approximately 8% should be a representative value of primary HIVDR in Thailand. Furthermore, we developed a new method and/or concept of primary HIVDR detection, the “short RT” genotypic resistance assay, to retain the efficiency of major resistance mutation detection while lowering the cost, thus making the test more accessible. The short RT is a simple in-house sequencing. To minimize the cost, we designed PCR and sequencing premiers to sequence only part of the pol gene. For the sequencing part, we employed a standard protocol for the conventional sequencing. This in-house short RT sequencing method is an alternative method for core facilities either resource-rich and resource-limited countries that currently use NNRTI-based regimens. Therefore, any resource-limited countries that have used either US FDA-approved HIV-1 DR genotyping system, in-house, or “home-brew” genotyping systems could easily utilize the short RT method. Lastly, this study is one of the largest to demonstrate the effect of primary HIVDR on treatment outcome.There are some limitations of our study. First, the patients were tested for HIV genotypes at pretreatment rather than at the time of diagnosis. Thus, some mutations may have reversed to the wild type, and the prevalence of primary HIVDR detected by “short RT” genotypic resistance assay could be underestimated. The prevalence of primary HIVDR among patients with recent HIV infection and those with chronic HIV infection might be different . Second,A moderate level of primary HIVDR was determined after a decade of rapid scaling up of ART in Thailand. Primary HIVDR was detected in approximately 8% of naïve HIV-infected Thai patients by a low-cost, “short RT” genotypic resistance assay. The presence of primary HIVDR, especially having M184I/V, is associated with detectable HIV RNA at 6 months after ART initiation. Routine “short RT” genotypic resistance assay for detection of primary HIVDR should be considered in Thailand to maximize treatment outcome.


The mean CD4+ count of patients was 501 (95% CI = 325–579) cells/cumm, but about 35% of patients had CD4+ T cell counts below 350 cells/cumm. With increasing age, average CD4+ count was found to be decreasing (p = 0.005). Of the total cases, 82 (9.92%) were found to have virological failure . Tenofovir/Lamivudine/Efavirenz (TDF/3TC/EFV), the frequently used ART regimen in Nepal, showed virological failure in 11.34% and immunological failure in 37.17% of patients. Virological failure rate was higher among children < 15 years (14.5%) (p = 0.03); however, no association was observed between ART outcomes and gender or route of transmission. The study suggests there are still some chances of virological and immunological failures despite the success of highly active ART (HAART).Antiretroviral therapy (ART) has increased the life span of the people living with HIV (PLHIV), but their virological and immunological outcomes are not well documented in Nepal. The study was conducted at a tertiary care center including 826 HIV-1 seropositive individuals undergoing ART for at least six months. Plasma viral load (HIV-1 RNA) was detected by Real Time PCR and CD4 The epidemic of human immunodeficiency virus type 1 (HIV-1) in Nepal is dynamic and concentrated among key populations at higher risk like people who inject drug (PWID), men who have sex with men (MSM) and transgender people, sex workers (SW), and male labor migrants ; however+ T cell measurements are recommended for resource-poor settings [+ T cell count (immunologic failure) or the recurrence of symptomatic HIV disease . Even then, clinicians may delay switching to second-line therapy, due to the limited availability of second-line medications and the poor specificity of CD4+ T cell counts and clinical symptoms for predicting virological failure [The primary goal of ART is to suppress HIV-1 RNA lower than the detection level (LDL) of the assay within six months on treatment and restore immunologic function, to reduce morbidity and mortality, to reduce vertical transmission, and to improve overall quality of life . Howeversettings . Due to  failure .+ T cell count, to assess HIV progression. In some situations, viral load may factor into decisions to initiate or change ART [Plasma HIV-1 RNA  testing quantifies the HIV viral burden in the plasma. The viral load is a standard tool used to monitor treatment response in patients taking ART and, in conjunction with the CD4ange ART . Studiesange ART .In Nepal, ART service was established in 2004 and viral load facility was started in 2009 through National Public Health Laboratory (NPHL). Phased scale-up has been planned to efficiently and successfully expand viral load testing services, taking into account the targets for enrollment of PLHIV into ART program. Based on the recommendations of Consolidated Treatment Guidelines of World Health Organization (WHO) and National Consolidated guideline on HIV prevention, treatment, and care, Nepal is at the incipient stage of HIV drug resistance and monitoring of early warning indicators [A descriptive cross-sectional study was conducted at National Public Health Laboratory from November 2013 to June 2015. Patients from four major ART service centers of Nepal, Teku ART Center, Kathmandu; Western Regional Hospital ART Center, Pokhara; Chitwan Hospital ART Center, Chitwan; and Lumbini Zonal Hospital ART Center, Butwal, were enrolled.Ethical approval of the study protocol was obtained from Nepal Health Research Council and 826 patients were recruited after obtaining written informed consent. HIV infected individuals under ART for a minimum of six months  and meeting the study criteria were enrolled.A standard data collection questionnaire was completed for each patient prior to sample collection. Patient's data including age, sex, ART sites, duration of ART treatment, and ART regimens used were collected at the sample collection site. The data were verified by using the ART center database maintained at ART sites as well as NPHL.+ T cell count and the other for HIV-1 viral load testing. For the latter, the tube with whole blood was centrifuged at 1500 RPM for 10 min, and plasma was separated, aliquoted, and stored at −20°C/−80°C. Plasma samples separated in the peripheral centers were stored at −20°C and were transported to NPHL on the same day of sample collection, where the plasma samples were stored at −80°C until analysis.Blood sample (5 mL) was collected by registered laboratory technicians/technologists/nurses using BD K3EDTA Vacutainers and disposable needles. The sample was divided into two separate vials: one for CD4μL) provided with the kits were used to develop standard curve for the quantification of the viral load copies per mL. Internal control was used to control the RNA isolation procedure and to check for possible PCR inhibition.HIV-1 RNA was extracted by using QIAamp Viral RNA Mini Kit  following the manufacturer's protocol. The eluted RNA was stored at −80°C until RNA quantification. HIV-1 RNA was quantified by Real Time PCR using artus HI Virus-1 RG RT-PCR Kit  and Corbett Rotor-Gene 6000 Real Time PCR system. The PCR conditions were set for denaturation 95°C/30 seconds, annealing 50°C/60 seconds, and elongation 72°C/30 seconds. A range of standards  using the anticoagulated whole blood following the manufacturer's protocol. Tru-COUNT reagent containing monoclonal antibodies for CD3, CD45, and CD4 labelled with fluorescent dyes  was mixed with anticoagulated whole blood and red blood cells were lysed with lysing solution before enumeration. BD MultiSET software (BD Biosciences) was used to determine the absolute CD4+ T cell counts.The enumeration of CD4+ T cell count < 350/cumm and viral load > 1000 copies/mL after six months of ART treatment were considered as cutoff for immunological and virological failures, respectively. The outcome was analyzed with respect to age, sex, route of transmission of HIV infection, and duration of ART by using Chi-square test and ANOVA.All the data were recorded in Microsoft Excel 2013. The statistical analysis was carried out by using SPSS 17.0 software and “Openepi” online software. CD4The study comprised a total of 826 PLHIV under ART for at least six months from different ART referral sites of the country; out of them 419 were males and 407 were females with male-to-female ratio of 1.03. The mean time duration of ART treatment was 59.7 months. The patients were representative of almost all regions of the country. The number of samples collected from the referral sites is shown in + T cell count = 501 cells/cumm; 95% confidence interval (CI) = 325–579 cells/cumm). With increasing age, the average CD4+ T cell count was found to be decreasing . Average CD4+ T cell count was 789 cells/cumm  in children below 15 years and 440 cells/cumm  in PLHIV more than 15 years  though statistically insignificant  HIV-1 viral RNA level , whereas 82 (9.92%) patients had shown virological failure (>1000 copies/mL). 129  patients had detectable viral load copies which were still below the threshold considered for virological failure. The average HIV-1 viral load was the highest  in the age group of 0–9 years . To address the fluctuating values of viral load, we compared different categories of CD4+ T cell levels and viral load levels, where we observed significant association between virological and immunological parameters (p = 0.028) with reciprocal relationship between them  compared to adults. However, no significant difference was observed in terms of gender and route of transmission. The immunological recovery was observed in 62.98% to 73.53% of the total study population depending upon the combination of regimens used. Similarly, virological suppression was manifested in 78.95% to 92.86% of the patients. Out of different regimens, TDF/3TC/NVP and AZT/3TC/NVP had better immunological and virological response among Nepalese PLHIV. These results are concordant with Chinese population, where 12.1% failure rate was observed with 3TC combined drugs [The ART regimens used in Nepal had shown good response in reducing the HIV-1 viral load. The failure rate observed in our study was concordant with the various studies conducted in other countries –15. The ed drugs .p = 0.04) in line with study results from India [Our study showed better outcome of Nevirapine based regimen than Efavirenz based regimen , drug resistance testing facility has not been yet available in the country, the patient's information was taken from the records retrospectively, and the failure rates were determined based on a single point testing of CD4


Highly active antiretroviral therapy (HAART) has extended life expectancy and enhanced the well-being of HIV-positive individuals. Since there are concerns regarding HAART-mediated onset of cardio-metabolic diseases in the long-term, we evaluated the anthropometric profile of black HIV-infected individuals in a peri-urban setting .A cross sectional study design was followed to describe the gender differences in different HAART treatment groups. HIV-positive patients  were recruited for three groups: 1) control , 2) HIV-positive (<3 years HAART), and 3) HIV-positive (>3 years HAART).All participants underwent comprehensive anthropometric and bio-electrical impedance analyses. No significant differences were observed in the male treatment groups. HAART-naïve females are mostly overweight (73.90 ± 2.79). This is followed by a period of muscle wasting seen in the triceps skinfold , muscle mass , and fat free mass  upon HAART initiation (<3 years HAART). Thereafter all parameters measured had levels similar to that seen for the female HAART-naïve group. Females on <3 years HAART exhibited significantly decreased body cell mass (p < 0.01), protein mass (p < 0.01), muscle mass (p < 0.01), fat free mass (p < 0.01), and fat mass (p < 0.001) versus matched HAART-naïve controls. The W:H ratio for the female treatment groups placed the females overall at a higher risk for developing cardiovascular disease compared to the males.This study found striking gender-based anthropometric differences in black South African HIV-positive individuals on HAART. We also conclude from this observational study that no significant differences were found in the different male treatment groups. All female body composition parameters initially showed lower values (<3 years HAART). The female treatment group (>3 years HAART) displayed values similar to that seen in the HAART-naïve group. Higher W:H ratios in females receiving longer-term HAART potentially increases their risk for the future onset of cardio-metabolic complications. South Africa is currently burdened with the highest global prevalence of HIV-AIDS, with ~6.4 million HIV-infected individuals making up ~12.2% of the population -6. In paPrevious studies show that HAART can trigger body composition changes leading to visceral fat accumulation in HIV-infected persons . MoreoveIn light of this paucity of data within the South African HIV-infected population, the current study assessed anthropometric changes within a peri-urban setting . We also set out to provide novel insights into the question of gender-based anthropometric changes in response to HIV-positive persons on HAART since this remains relatively poorly understood.This cross-sectional study was performed during 2012 and 2013 and evaluated gender-based body composition differences between HIV-positive HAART and HAART-naïve individuals. Black South African males and females n = 146) were randomly recruited and selected from ~1, 500 out-patients at the TC Newman Community Day Care Centre and the Mbekweni Clinic from the Paarl and Wellington health districts, respectively. Paarl and Wellington are closely located neighboring towns within a peri-urban setting, and located ~35 miles from Cape Town . HIV positive males or females that are on treatment, and/or newly diagnosed HIV patients (for controls); age ranges between 20 and 40 years; residents of Paarl, Wellington and the Drakenstein region were included in the study. No pregnant or lactating females or patients diagnosed with acute diseases were entered into the study. Participants were subsequently divided into two arms i.e. a) HAART-naïve control group , and b) HIV-positive HAART groups , respectively. The HAART group was further split into two sub-groupings, i.e. HAART for less and longer than three years, respectively. Such sub-groups were subsequently analyzed in a gender-dependent manner. We employed this particular sub-group classification based on previous research that found that HAART-induced anthropometric and metabolic alterations manifested in a temporal manner [6 were raBoth the Human Research Ethics Committee of Stellenbosch University and the Western Cape Government Ethics Committee approved this study (S12/03/073 and 2012 RP 100). Written consent was obtained from all participants after volunteering and agreeing to take part in the study. Participants were also free to withdraw from the study if they no longer wished to continue and had access to their standard medical care throughout the duration of the study.2) and waist-to-hip (W:H) ratio were calculated by employing the parameters here described. The triceps skinfold (TSF) was measured using a skinfold caliper , and the TSF site was located at the point on the posterior area of the right arm in the mid-line of the level of the mid-acromiale radiale landmark.All participants were informed of the physical testing procedures. Conventional anthropometry was performed in duplicate and included base measurements, circumferences and skin folds. Height was measured to the nearest 0.1 cm with a portable stadiometer , while weights were determined  to the nearest 0.01 kg using a calibrated Seca 634 scale . Waist circumference (WC) was measured with a Lufkin® executive thin line tape measure (Lufkin W606PM) . The circumference was determined at the narrowest point between the lower costal border and the top of the iliac crest perpendicular to the long axis of the trunk . The hipBio-electrical impedance analysis (BIA) was completed by employing a Maltron Bioscan 9200 standard tetra-polar multi-frequency analyzer  that analyzes the percentage fat, fat mass, body cell and muscle mass. Here a BIA pre-test protocol was implemented, i.e. a) emptying of the bladder, and b) removal of all metal objects from the skin. In addition, participants were instructed to lie on the examination bed with their legs and arms slightly apart with no limbs touching the body, while conduction electrodes were placed on both the right hand and right foot.post-hoc test was subsequently used to assess the significance of differences found between groups. We also completed additional analyses with the W:H data (as marker of fat distribution), i.e. Spearman correlation co-efficient was performed on W:H and CD4 cell counts. P-values of ≤ 0.05 were considered statistically significant and the mean ± SEM was used for all results reported.Statistical analyses were performed using Statistica version 12 software . The means, standard deviations and standard error of the mean (SEM) were calculated for all parameters, and factorial analysis of variance (ANOVA) employed to evaluate differences between various groupings and sub-groupings here investigated. The Bonferroni Of the 146 participants included, most were female n = 102; 70%) with a mean patient age of 30.9 ± 0.58 years, compared to 30% males (n = 44) with a mean patient age of 33.3 ± 0.69 years  for both genders. Here factorial analysis of variance (ANOVA) indicated a main effect of gender p < 0.001), and treatment and gender (p < 0.05). Overall, females displayed significantly larger TSFs compared to males irrespective of treatment status , gender (p < 0.001) and treatment and gender (p < 0.05)  Figure B.Figure Similar findings were established for PM, and a main effect of treatment (p < 0.05) was evident according to factorial ANOVA Figure C. In linWe also performed correlations for W:H ratio versus CD4 count (between genders) for the HAART-naïve and HAART  groups, respectively. The HAART-naïve group did not reveal any significant correlation between W:H ratio and CD4 count for males or females  weight levels return to baseline levels. Although not significant overall, the females  displayed elevated W:H ratios after prolonged HAART, therefore potentially putting them at increased risk for the future onset of cardio-metabolic complications.Our finding that the majority of black HIV-positive women (at start of HAART) displayed obesity is in broad agreement with others  who repoet al. [We also found elevated TSF values in females compared to males indicating an elevated risk for obesity and related cardiovascular risk. Moreover, when the total group was sub-divided into HAART-naive, <3- and >3 years HAART distinct differences were observed only in the female treatment categories. These findings are in agreement with others who found significantly lowered TSF values in Indian female HIV-positive patients following 12 months of HAART . Likewiset al.  reportedet al. . For theet al. . Howeveret al. . Such fiet al. . HoweverLiterature suggests that both TSF and mid-upper arm circumference (MUAC) are independent predictors for survival, and surrogate parameters for muscle wasting ,25. BothMuscle mass, FFM and FM did not significantly differ in males for the different HAART groups compared to the HAART-naïve one. Although there is a tendency for weight loss amongst males in the <3 year HAART compared to the HAART-naïve group (p = 0.08) (data not shown), the variability in weight in the >3 year HAART group makes comparisons non-significant. However, inclusion of more subjects  may shed greater light on this question.Waist-to-hip ratios were also assessed as a marker for cardio-metabolic risk ,27. FemaWe acknowledge that the present study has some limitations, one being the intrinsic limitation of a cross-sectional design. Although our findings demonstrated clear gender-based differences, another limitation is the relatively low number of male participants . This observation is in accordance with previous work where males were also less likely to attend clinics and participate in research studies . This isThe current study established unique gender-based differences in a peri-urban black South African HIV-infected population. Unlike males, females displayed initial muscle wasting but thereafter gained weight (significantly higher W:H ratios) with prolonged treatment. Thus these data suggest that female HIV-positive individuals on longer-term HAART may be at greater risk for the development of cardio-metabolic disease complications. Future studies should focus on determining the cause of the body compositional changes undergone with treatment duration and distinguish between the influence of HIV itself and the treatment thereof. The multiple anthropometric and body compositional characteristics described provided robust insights into changes observed with increasing HAART duration. This reinforces the importance of basic anthropometric measurements that are fairly quick, cost-effective and easy to perform in peri-urban and rural settings to aid in identifying patients at risk for HAART-related co-morbidities.


To assess efficacy and safety of treatment simplification to co-formulated Rilpivirine/Emtricitabine/Tenofovir (RPV/FTC/TDF) in virologically suppressed patients.Endpoints of the analysis were: (a) treatment discontinuation of RPV/FTC/TDF for any reasons and (b) occurrence of virological failure (VF) defined as confirmed HIV-RNA >50 cp/mL).Overall, 508 patients from five Italian reference centres were included: male gender 71.9%; median age 47 years (IQR 40–52); IVDU as HIV risk 17.7%; HCV-AB positive 23.4%; CDC-C stage 17.5%; median CD4 cells/µL at switch 655 (IQR: 487–843); median number of previous regimens three (IQR 2–7). In a median follow-up of 196 days (IQR: 84–287), 31 patients discontinued RPV/FTC/TDF . Moreover, VF occurred in eight patients . At survival analysis, the probabilities of treatment discontinuation or VF were 5.5% and 1.2% at 6 months, 13.2% and 2.8% at 12 months, respectively . At adjuOur data suggest that switching to RPV/FTC/TDF in virologically suppressed patients could be a good strategy with low risk of virological failure or treatment discontinuation; the switch is also associated with significant improvement in lipid profile.