Genotypic tropism testing (GTT) has been developed largely on HIV-1 subtype B. Although a few reports have analysed the utility of GTT in other subtypes, more studies using HIV-1 subtype C (HIV-1C) are needed, considering the huge contribution of HIV-1C to the global epidemic.Plasma was obtained from 420 treatment-naïve HIV-1C infected Ethiopians recruited 2009–2011. The V3 region was sequenced and the coreceptor usage was predicted by five tools: Geno2Pheno clinical–and clonal–models, PhenoSeq-C, C-PSSM and Raymond’s algorithm. The impact of baseline tropism on antiretroviral treatment (ART) outcome was evaluated.Of 352 patients with successful baseline V3 sequences, the proportion of predicted R5 virus varied between the methods by 12.5% (78.1%-90.6%). However, only 58.2% of the predictions were concordant and only 1.7% were predicted to be X4-tropic across the five methods. Compared pairwise, the highest concordance was between C-PSSM and Geno2Pheno clonal (86.4%). In bivariate intention to treat (ITT) analysis, R5 infected patients achieved treatment success more frequently than X4 infected at month six as predicted by Geno2Pheno clinical  and at month 12 by C-PSSM . However, in the multivariable analysis adjusted for age, gender, baseline CD4 and viral load, only tropism as predicted by C-PSSM showed an impact on month 12 .Each of the bioinformatics models predicted R5 tropism with comparable frequency but there was a large discordance between the methods. Baseline tropism had an impact on outcome of first line ART at month 12 in multivariable ITT analysis but only based on prediction by C-PSSM which thus possibly could be used for predicting outcome of ART in HIV-1C infected Ethiopians. Human immunodeficiency virus type 1 (HIV-1) enters cells through the use of the CD4 receptor and one of the two coreceptors, CCR5 or CXCR4 . These vStudies validating GTT report decreased sensitivity to detect X4 tropic viruses and differences between subtypes when compared to phenotypic assays . We receThe increasing influx of migrants to European countries has resulted in an increase of compartmentalized epidemics of non-B subtypes and recombinants forms , especiaA cross-sectional study was conducted on a random subsample of ART naïve adults (age >16 years) (n = 420) enrolled in the large countrywide Ethiopian Advanced Clinical Monitoring of HIV (ACM) cohort, recruited between 2009 and 2011, 15. TheThe plasma samples were temporarily stored at -20°C at each site, transported to the central laboratory of the Ethiopian Health and Nutrition research institute (EHNRI) and stored at -80°C. HIV-1 RNA load (VL) was analysed by MT 2000 real time PCR  and CD4+ T-cell count was enumerated using FACSCount (Becton Dickenson), according to standard operating procedures at EHNRI.Ethical approval for the study was obtained from the Ethiopian Ministry of Science and Technology and the EHNRI institutional review board. Written informed consent was obtained from all participants.env gene encoding the V3-V4 region was amplified from cDNA based on a nested PCR protocol as described previously [Et . The first-round PCR was performed with primer ED5 (forward) 5’-ATGGGATCAAAGCCTAAAGC CATGTG-3’ (HXB2 nt 6556–6581) and ED12 (reverse) 5’AGTGCTTCCTGCTGCTCCCAAGA-ACCCAAG-3’ (HXB2 nt 7822–7792) primers to amplify 1200 bp, and inner primers were Et_ES7 (forward) 5' TTRTTAAATGGTAGTATAGC-3' (HXB2 nt 7001–7020) and ES8 (reverse) 5’-CACTTCTCCAATTGTCCCTCA-3’ (HXB2 nt7647-7667) to amplify 650 bp. Second round PCR amplicons were purified using QIAquick kit (Qiagen) followed by bidirectional population sequencing in automated sequencer . Sequences results were aligned, edited, and analyzed using the BioEdit software v.7.0.9.HIV-1 RNA was extracted from plasma using QIAamp Viral RNA kit , according to the manufacturers' instructions. cDNA was synthesized using RevertAid H-minus reagents  following the manufacturer’s instructions (Life technologies). The eviously and with Prediction of coreceptor usage was performed using five bioinformatics tools: Geno2Pheno clinical–and clonal–models , PhenoSeAs bulk sequencing often produces sequences with sites of ambiguity whereby two or more nucleotides occur with similar frequency, V3-nucleotide sequences were used as input for PhenoSeq-C, which along with the tropism prediction converts bulk nucleotide V3 sequences containing ambiguity into multiple unambiguous amino acid sequences, by generating and translating all possible nucleotide combinations . The obtBaseline socio-demographic and laboratory characteristics  were analysed. The treatment outcome was assessed with both intention-to-treat (ITT) and on-treatment (OT) analysis. In the ITT analysis, ART failure was defined as either detectable VL (>1000 copies/ml), death or lost-to-follow-up (LTFU). In the OT analysis, we include only those who had actual VL data at the follow up time points and excluded patients who were dead or LTFU. Descriptive analyses included frequencies for categorical variables, mean and standard deviation or median and interquartile range for continuous variables. Chi-square test or Fisher’s Exact Test were used to test differences between categorical variables. Independent t-test, Mann-Whitney, Anova and Kruskal-Wallis test assessed differences of numerical variables between two or more categories. Logistic regression models were used for the multivariable analysis of virological responses to compare differences between R5 and X4 infected patients as predicted by 4 different methods, adjusting by age and gender, baseline CD4+ T-cell count and VL. Odds Ratios (OR), 95% Confidence interval and p-values were used to present the regression models results. Results were adjusted for design effect due to the cluster nature of the study design. P-values<0.05 were considered significant. Data analysis was done by the STATA software 13  and IBM SPSS Statistics, version 22 (IBM Corp).At baseline V3 loop sequencing was successful in 352 of 420 (84%) patients. No difference was found in viral load or other characteristics between patients who had a successful sequencing or not. The length of the V3 loop was 35 amino acids (aa) in 333 (94.6%) of the 352 sequences while 15 sequences were 34 aa, two sequences 37 aa long, two sequences 36 and 38 aa each. HIV-1C was found in 350 (99.4%) patients and A1 in two (0.6%) patients.Patients predicted to be infected with R5 or X4 strains were compared with regard to age, gender, CD4+ T-cell count and VL at baseline. No statistically significant difference was found for any comparison, except for the Geno2Pheno clinical model where the CD4+ T-cells were higher in R5 patients  .There was a tendency to higher CD4+ T-cells in R5 patients also for the Geno2Pheno clonal model (p = 0.09) and the C-PSSM (p = 0.067), but not for PhenoSeq-C.The proportion of patients predicted to be infected with R5 virus varied between the methods by 12.5%, the highest (90.6%) by Raymond’s algorithm and the lowest (78.1%) by PhenoSeq-C . Also, tThe viral tropism of the patients who failed virologically at month six and 12, respectively, were predicted. At month six (n = 34), the overall concordance was 24/34 (70.6%) with PhenoSeq-C and Geno2Pheno clonal model showing the highest concordance (94.1%) . For virOf the 352 patients, 33 patients had died, 28 were LTFU and 15 had a missing VL, at month six. Of the remaining 276 (78.4%) patients, 37 (12.7%) had >1000 copies/ml . By OT bivariate analysis, there was no significant difference in achieving viral suppression at month six between patients with R5 or X4 virus at baseline, by any method .Among the 33 patients who were reported to have died at month 6, the proportion of X4 infected patients was 42.4%, 27.3%, 15.2%, 33.3% and 15.2% by G2P clinical, G2P clonal, PhenoSeq-C, C-PSSM and Raymond respectively. Among the 28 LFTU patients he corresponding figures were 14.3% for G2P clinical, G2P clonal and PhenoSeq-C, 17.9% for C-PSSM and 3.6% for Raymond. When patients were grouped as alive, dead or LTFU at month 6, a statistically significant difference (p = 0.001) was found between the groups only when tropism was predicted by G2P clinical.At month 12, a further 10 patients had died, 28 were LTFU and 55 patients had a missing VL . Of the remaining 198 (56.3%) patients, 22 patients (8.6%) had > 1000 copies/ml and 55 (21.7%) had missing VL. Thus, 176 out of 352 (50.0%) reached treatment success in an ITT–analysis at month 12. By OT bivariate analysis, X4 infected patients, predicted by C-PSSM, achieved viral suppression less frequently although the difference was not statistically significant . However, no difference was shown between R5 and X4 infected patients at months six and 12 in multivariable OT analysis .In bivariate ITT analysis, a significant difference in treatment outcome between R5 and X4 infected patients was observed at month six by the Geno2Pheno clinical model  and at month 12 by C-PSSM  .The Geno2Pheno clinical tool finding did not remain significant in the multivariable analysis, when adjusted by age, gender, baseline CD4 and VL. Instead, tropism as predicted by C-PSSM had an impact on month 12 in ITT by the multivariable analysis, with patients with R5 tropism 2.47 times more likely to achieve VL suppression compared to patients with X4 tropism  .At month six, virological failure occurred in 37 randomized patients and in seven non-randomized additional patients who were included only for the study of coreceptor switch. Plasma samples at baseline and at failure were available in 41 of them. At baseline, V3 sequencing was successful in 34 patients. The most frequent R5 tropic virus prediction was by Raymond’s algorithm  and the lowest rate by C-PSSM . The most frequent rate of tropism switch  was described by C-PSSM . For the PhenoSeq and Geno2Pheno clonal tools, 4/34 strains switched each (two R5 to X4 and two X4 to R5). For Raymond’s algorithm, 4/34 strain switched At month 12, 22 subjects failed virologically in whom V3 sequencing was successful in 19. Of these, nine had also a failure at month six. In most patients, the same tropism was found at month 12 as at baseline .HIV-1C contributes to more than 50% of the global epidemic and is the dominating non-B subtype among newly diagnosed in several European countries, e.g Sweden , IcelandThe bioinformatics methods have been developed largely on HIV-1B data, although PhenoSeq-C  and C-PSWhen comparing the prediction tools pairwise, the C-PSSM and Geno2Pheno clonal models were highly concordant (86.4%), in line with previous studies which demonstrated the best concordance (>85%) between these two tools among several –34. A V3Data regarding impact of baseline tropism on first line, non-maraviroc containing, ART outcome are scarce. Some reports have described poorer viral load suppression or CD4+ T cell increase in patients with X4 virus at baseline –38, whilThere are some shortcomings in our study. We classified patients who were predicted to have a mixed R5X4 infection as having X4 virus in the statistical analysis, despite that no clonal analysis was done, since X4 viruses are uncommonn in HIV-1C patients. However, only 2% of the samples exhibited such a pattern by each prediction method and did not affect the results. We did not compare our genotypic data with a phenotypic method which is usually considered as a gold standard so that determination of sensitivity and specificity of the GTT methods for HIV-1C was not possible. However, the purpose of our study was rather to compare the results with clinical information in the largest cohort of HIV-1C patients analysed so far with GTT. Consequently, we could not identify a single GTT, which correlated best to clinical outcome in HIV-1C patients, although tropism predicted by C-PSSM correlated to outcome at month 12 in an ITT analysis. Moreover, we did not adjust for multiple comparisons since this study focused on only a few scientifically sensible comparisons, rather than every possible comparison. For this reason there is a risk of false positive findings.Each of the GTT predicted R5 tropism with comparable high frequency in HIV-1C infected Ethiopians, but there was a large discordance and only 1.7% were X4-tropic by all five methods. Baseline tropism had an impact on outcome of first line ART in only multivariate ITT analysis based on C-PSSM, at month 12, although no difference was found at month 6. Thus, among all of the tropism prediction methods tested, C-PSSM could possibly be used to predict outcome of ART in HIV-1C infected patients.S1 File(XLSX)Click here for additional data file.


The aim of this study is to analyse the clinical features of HIV patients with cytomegalovirus retinitis (CMVR) developing immune recovery uveitis (IRU) while on highly active antiretroviral therapy (HAART) and to identify the risk factors, visual outcomes and complications of IRU.n = 26, 86.7 %) of patients were male, with 76.7 % (n = 23) of patients having bilateral disease. Twenty-seven eyes (50.9 %) had both anterior uveitis and vitritis. The median CD4 at IRU was 210 cells/μL (IQR 140–279), with 86.7 % having CD4 >100 cells/μL. The median duration from initiation of HAART to IRU was significantly different between those <50 years old  and those ≥50 years old . Fourteen eyes (26.4 %) had loss of one or more Snellen lines visual acuity at 6 months while the rest maintained or improved vision. Complications developed in 21 eyes, with cataract (66.7 %), glaucoma and ocular hypertension (33.3 %) being the most common. The risk of complications was associated with the absolute difference in CD4 counts at IRU and at HAART commencement (p = 0.041). Age was also negatively associated with the duration from HAART to IRU .Majority (It is common to have both anterior uveitis and vitritis in IRU. There was a positive association between the increase in CD4 from HIV to IRU diagnoses and the risk of developing complications. Younger patients appeared to develop IRU later than older patients after HAART, suggesting that long-term follow-ups are essential for these patients. Immune reconstitution inflammatory syndrome (IRIS) is a group of disorders that has been described in HIV patients who are on highly active antiretroviral therapy (HAART). This phenomenon is associated with a paradoxical or exaggerated reactivation of the immune system in the background of a wide range of pathologies such as Kaposi’s sarcoma, tuberculosis, cryptococcal infection and cytomegalovirus .Immune recovery uveitis (IRU) is one manifestation where immune-deficient patients with prior cytomegalovirus retinitis (CMVR) experience an increase in intraocular inflammation following HAART. It is presumed to be mediated by the recovery of immune responses specific to residual cytomegalovirus (CMV) antigens in the eye . IRU is A retrospective analysis of clinical records of 30 consecutive IRU patients presenting to the Eye Clinic at the Communicable Disease Centre (CDC), Singapore, between March 2004 and September 2009 was performed. Ethics approval was obtained from the local ethics review board in accordance with the Declaration of Helsinki.The CDC is the main site of referral and management for HIV in Singapore. IRU was diagnosed when there is an increase in any form of intraocular inflammation from an inactive state of CMV retinitis secondary to immune recovery after initiation of HAART, as evidenced by an increase in CD4 count by 50 or more cells/μL from the nadir CD4 count to a level of more than 100 cells/μL . DespiteAll of the patients had prior CMV retinitis treated with an intravitreal ganciclovir regimen, as previously described . Two patt test and Mann-Whitney U test were used for comparison of age, durations and CD4 counts between patient groups with and without complications, respectively. Logistic regression was used to understand the relationship between variables. A p value less than 0.05 was considered to indicate statistical significance. Data analysis was carried out using IBM SPSS Statistics .Descriptive analysis was performed for demographics, visual acuity, complications and IRU and CMVR characteristics, with categorical variables summarised with frequencies and percentages and continuous variables summarised as either means with standard deviations or medians with ranges. Spearman’s rho was calculated to check for association between CD4 counts and durations. Independent sample n = 25) formed the majority, corresponding to the ethnic distribution of the local population [n = 53) with previous CMVR, in this cohort, developed IRU. Twenty-three patients (76.7 %) presented with bilateral IRU. Twenty-seven IRU eyes (50.9 %) presented with both anterior uveitis and vitritis. Twenty-two IRU eyes (41.5 %) presented with anterior uveitis alone, while one eye (1.9 %) presented with only vitritis. The median CD4 count at HIV diagnosis of these patients was 20 cells/μL (IQR 15.0–62.0), while the median CD4 count at IRU diagnosis was 210 cells/μL (IQR 140–279), with 86.7 % having CD4 >100 cells/μL. Two of the four patients with CD4 count less than 100 cells/μL had more than 50 cells/μL increase in CD4 count at IRU diagnosis. The median increase in CD4 at IRU was 155.5 cells/μL (IQR 66.0–228.0). The median duration from HIV diagnosis to initiation of HAART was 100.5 days (IQR 61.0–210.0), while the median duration from initiation of HAART to IRU was 214 days (IQR 118.0–763.0). Thirteen IRU patients (43.3 %) were asymptomatic at presentation. Of the remaining 17 IRU patients, the most common symptom was blurring of vision alone  followed by floaters . All patients were treated with topical steroids, with eight patients requiring additional sub-tenon steroid injections and two patients receiving oral steroids (Tables Twenty-six patients (86.7 %) were male, and the median age at IRU diagnosis was 49.5 years old (interquartile range (IQR) 41–56 years). Chinese patients  had previous CMVR involvement in zone 2. This was followed by zone 1 CMVR involvement in 15 eyes (28.3 %) and zone 3 involvement in 11 eyes (20.8 %). The majority of eyes  had <25 % area of involvement, while nine eyes (17.0 %) had 25–50 % area of involvement and four eyes (7.5 %) had >50 % area of involvement (Table All of the patients had CMVR in at least one eye. Fifty-three of the 60 eyes 88.3 %) had previous CMVR. The median duration from HIV diagnosis to CMVR was 283.0 days (IQR 142.0–539.5), while the median duration from CMVR diagnosis to anti-CMVR treatment was 0 days (range −2 to 16), with 24 patients receiving treatment on the same day as CMVR diagnosis. The median CD4 count at CMVR diagnosis in our patients was 28.5 cells/μL (IQR 11.0–60.5). Most eyes  having BCVA worse than 6/12. At 6 months, 18 eyes (34 %) had BCVA worse than 6/12. Six (11.3 %) and two eyes (3.8 %) had a loss of one and two Snellen lines, respectively. Six eyes (11.3 %) had a loss of three Snellen lines or more. These were due to glaucoma, cataract or persistent inflammation. The remaining patients had visual acuities that were maintained or better than at IRU presentation , followed by glaucoma and ocular hypertension . There were no cases of CME during the course of this study. Mann-Whitney U test showed an association between the presence of complications and the absolute difference in CD4 counts at IRU and at HAART commencement (p = 0.041). For every 50 cells/μL increase in CD4 at IRU diagnosis, patients were 1.28 times more likely to develop complications (p = 0.084). Although not statistically significant, the higher CD4 count at IRU diagnosis also appeared to be associated with the development of complications (p = 0.057). CMVR characteristics (zone and area of involvement) were not found to be associated with the development of complications .Twenty-one eyes (39.6 %) developed complications. The most common complication was cataract . Median duration from HAART initiation to development of IRU was 763 days (IQR 174–1872 days) and 161 days (IQR 84.5–278 days) for patients <50 years old and patients ≥50 years old, respectively. The CD4 counts at HIV diagnosis, at initiation of HAART and at IRU diagnosis were not found to be significantly associated with the duration from HAART to IRU diagnosis. Both the absolute and the percentage increase in CD4 counts were also not significantly associated with the duration taken to develop IRU after initiation of HAART. CMVR zone or area of involvement was not found to be associated with the duration of IRU development from initiation of HAART.Age was found to be negatively associated with the duration taken to develop IRU after initiation of HAART . Hartigan-O’Connor et al. previously reported that IRU is most likely to develop in patients with the greatest degree of immune dysfunction prior to HAART . AdditioThe most common complications of IRU in our cohort were cataract formation, glaucoma and ocular hypertension. Our findings differ from other reports where CME and epiretinal membrane were the most common complications. For instance, Robinson et al. reported that of the IRU eyes in their cohort, 91 % developed CME, 52 % developed cataract and 30 % developed epiretinal membrane .No cases of CME were reported during the course of this study. Although CME is often described and is a serious sight-threatening complication of IRU, we believe that it is not a common feature, especially if the inflammation is treated earlier. This is particularly pertinent as there is currently no consensus on the ideal time to start treatment of IRU. In fact, the majority of studies have suggested that mild and asymptomatic ocular inflammation usually resolves without treatment; treatment is instituted in more severe inflammation and in patients who become symptomatic , 8.IRU has been described as a transient form of inflammation . Still, The risk of IRU complications was found to be higher with greater CD4 count increase from HIV to IRU diagnosis. The greater inflammatory response mounted in these immune reconstituted patients, together with a robust increase in the number of viable T lymphocytes, results in severe and chronic inflammation . The incn = 39) had either maintained or improved in vision. The importance of early diagnosis with aggressive and appropriate treatment can improve and preserve vision. Moreover, a number of patients were asymptomatic and were found to have IRU only on routine follow-up examinations. All HIV patients with treated CMVR should continue to have regular reviews at the eye clinic at regular intervals, even if they have high CD4 counts. Our study showed the median time from commencement of HAART to IRU development to be about 7 months. The longest time taken was 8.8 years in a 25-year-old female. Without regular follow-up, early recognition and treatment, the visual outcomes of these patients may be less favourable.The presence of IRU at baseline was reported to be associated with an increased risk of moderate vision loss to 6/15 . The visThe main limitations of this study were its retrospective design and relatively small sample size. There was also no control group. Unlike other studies, we did not routinely perform angiogram on our patients. Hence, it is possible that early CME not apparent on physical examination was missed. Nonetheless, our cohort of patients was diagnosed consecutively from the CDC, which is reflective of the HIV patient profile in Singapore, as the CDC is the main centre for HIV treatment.IRU is common and usually presents with vitritis. Early treatment of ocular inflammation can prevent the development of sight-threatening complications of IRU. The most common complication is cataract formation, and the risk of complications was positively associated with the increase in CD4 count at IRU and HIV diagnosis. Younger patients also appeared to develop IRU later than older patients after HAART, emphasising that long-term follow-ups are essential for these patients.


Purpose. The purpose of this study was to evaluate the ocular disorders in HIV positive patients attending the Cape Coast Teaching Hospital, Ghana. Methods. A cross-sectional study using systematic random sampling was conducted on 295 HIV positive patients. Data collection consisted of semistructured questionnaires, laboratory investigation, medical profile, and ophthalmic examination. Statistical association tests including χ2, independent t-test, and ANOVA were done. A p value ≤ 0.05 was considered statistically significant. Results. Of the 295 participants, 205 (69.5%) were on antiretroviral therapy while 90 (30.3%) were not on therapy. Majority of the participants  were in clinical stage two, followed by stages three , one , and four , respectively. The overall prevalence of ocular disorders was 5.8%. The most common HIV related ocular disorder was HIV retinal microvasculopathy (58.8%), followed by herpes zoster ophthalmicus and Toxoplasma retinochoroiditis, both representing 11.8% of ocular disorders seen. Cytomegalovirus retinitis, Bell's palsy, and optic neuritis were the least common (5.9%). CMV retinitis recorded the highest viral load of 1,474,676 copies/mL and mean CD4 count of 136 cells/mm3. The mean CD4 count for participants with HIV related ocular disorders was significantly lower compared to participants without disorders . Participants with ocular disorders also recorded significantly higher mean viral loads than those who did not have ocular disorders . Conclusion. Lower CD4 counts and high viral load copies were associated with the manifestation of HIV related ocular disorders. Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV) which affects all body organs either directly or by opportunistic infections, and the eye is not spared. AIDS indicates advanced HIV disease in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive . OpportuThere is a huge dearth of information in Ghana on ocular related findings in HIV patients. Reports from other societies have always considered the associations between HIV related ocular manifestations and CD4 counts but not viral loads. The purpose of this study was to evaluate the associations between presenting ocular disorders and CD4 counts/viral load copies in HIV positive patients attending the Cape Coast Teaching Hospital, Ghana.The study was carried out at the Antiretroviral Therapy (ART) Specialist Clinic of the Cape Coast Teaching Hospital in Ghana. The Cape Coast Teaching Hospital, one of the five teaching hospitals in Ghana, provides health services to people in the central and western regions and parts of Ashanti and eastern regions. It also has the mandate of training doctors and other medical staff.N = Z2(1 − p)(p)/b2 [N is the minimum sample size, z is the standard normal deviation, usually set at 1.96 which corresponds to the 95% confidence interval, p is the proportion in the target population estimated to have the infection , and b is the degree of accuracy desired, usually set at 5%. Consequently, a sample size of 30 was calculated. This was adjusted to 200 participants to account for attrition rate and inefficiencies associated with the sampling method. A systematic sampling method was used to recruit clinically diagnosed HIV patients, who attended the ART Specialist Clinic between January and May 2016. Based on the average daily attendance at the clinic and a determined sampling interval of three (3), the first participant was chosen by randomly selecting a number between one and three. Every third patient from the first participant was then recruited into the study. In all, 320 patients were examined within the period. Out of them, 295 patients had complete medical data and they were included in the analysis. Patients who had comorbidities such as diabetes, hypertension, and sickle cell disease were excluded from the study.The study employed a descriptive cross-sectional design. Sample size was determined based on the expression p)(p)/b2 , where NThe study was conducted in accordance with the Helsinki Declaration on Research Regarding Human Subjects. Ethical clearance (ID number UCCIRB/CHAS/2015/090) was obtained from the Institutional Review Board of the University of Cape Coast. The rationale of the study was comprehensively explained to all participants after which consent forms were issued to them to sign, including local language versions which were read out to illiterate subjects who consented with a thumbprint prior to investigation. For participants below 18 years of age whose assent was sought, their parents/guardians signed the consent forms on their behalf. The participants were assured of confidentiality and safety at all times. They were also reminded of the voluntary nature of the study which granted them the right to withdraw at any point.The method of data collection consisted of semistructured questionnaires, laboratory investigation, medical profiles, and ophthalmic examination. Every consenting patient was assigned a specific study code. A trained investigator interviewed and filled the questionnaires for all the participants. Information obtained from the questionnaires included age, gender, occupation, religion, marital status, level of education, and duration of infection from the time of diagnosis. The patient's HIV related medical information such as the World Health Organization (WHO) clinical stage of the disease, whether the participant was on ART or not, and duration of ART usage was recorded.About 3 mL of venous blood was collected from each participant and HIV biomarkers CD4 counts and viral loads were determined. Two CD4 counts were obtained for this study: nadir CD4 counts (the lowest CD4 count ever recorded) and the current CD4 counts (CD4 counts at the time of the study). It was important to evaluate both the nadir and the current CD4 counts in this study to appreciate the effect of antiretroviral therapy on CD4 and to ascertain the stage at which some HIV related ocular disorders actually occurred.Ophthalmic examination was conducted by experienced eye care personnel. Presenting Distance Visual Acuity (PDVA) measurements followed by slit lamp biomicroscopy and dilated funduscopy were performed on all participants. Pinhole acuity was performed to rule out refractive error as the cause of reduced vision. Dilated fundus examination was performed with 2.5% phenylephrine ophthalmic solution. Two drops of the phenylephrine were administered at an interval of 5 minutes followed by one hour of waiting to ensure maximum papillary dilation. Ophthalmoscopy was then performed on each participant. Ophthalmic examination forms were correspondingly labeled for each participant. Categories of visual impairment (VI) were determined based on the International Classification of Diseases, where “low vision” is defined as presenting visual acuity < 6/18 in the better eye .χ2) test was used to determine the associations between categorical variables. Fisher's exact test was used where counts were less than 5. Independent t-test and analysis of variance (ANOVA) were performed to compare the mean values of HIV biomarkers  between participants who had HIV related visual disorders and those who did not. A p value ≤ 0.05 was considered statistically significant.The data collected were entered into SPSS for Windows, version 21.0.1. The analysis involved the use of frequency distribution tables. Chi-square . The mean current CD4 count of participants on ART was lower (786.5 cells/mm3) than of participants not on ART (863.8 cells/mm3). This difference was, however, not significant . Similarly, there was no significant difference between the mean viral load counts for participants on ART and those not on ART .A total of 320 patients were examined within the period, out of whom 295 had complete medical data and were included in the analysis. They comprised 78 (26.4%) males and 217 (73.6%) females. Their ages ranged from 10 to 83 years with mean age of 45.3 years (SD: ±11.6). According to the WHO criteria on HIV classification, majority of the participants  were in clinical stage two, followed by stages three, one, and four that had 68 (23.1%), 62 (21%), and 3 (1%) participants, respectively. Two hundred and five (69.5%) of the participants were on antiretroviral therapy while the remaining 90 (30.5%) were not on therapy. The mean age of participants on ART was 45.9 (SD: ±11.64) years while those not on ART had a mean age of 43.8 (SD: ±11.46) years. There was no statistically significant difference between the mean ages of participants on ART and those without therapy .Majority of the participants  had normal vision of VA 6/6. One hundred and sixteen (39.3%) had mild visual impairment (VA 6/9–6/18). Twenty-nine (9.8%) of the participants had low vision (VA < 6/18) out of whom 19 (65.5%) were on antiretroviral therapy. Five (17.2%) of the 29 participants were in the first clinical stage of the disease whereas 19 (65.5%) and 5 (17.2%) were in stages two and three, respectively. Low vision occurrence was lower in the ART group (9.8%) than in the non-ART group (11.1%). However, there was no significant association between low vision and ART status (p = 1.00), age (p = 0.60), occupation (p = 0.38), and duration of infection from the time of diagnosis (p = 0.81). There was also no significant difference between the mean ages of patients who manifested ocular disorders and those who did not .Out of the 295 participants who took part in the study, 17 (5.8%) had HIV related ocular disorders of whom three were bilateral cases . Of these 17 participants, 4 (23.5%) were males and the remaining 13 (76.5%) were females. There was no significant association between manifestation of ocular disorders and sociodemographic factors such as gender  of the ocular disorders found. Participants who had HZO recorded a mean CD4 count of 269 cells/mm3 and mean viral load of 38,090 copies/mL. Cytomegalovirus retinitis was responsible for only 1 (5.9%) case and it occurred in a participant with a CD4 count of 136 cells/mm3 and the highest viral load count of 1,474,676 copies/mL. Neuroophthalmic disorders found were Bell's  palsy and optic neuritis, each accounting for  of the cases. F = 362.7, p < 0.001) where CMV retinitis was associated with the highest viral load copies. However, the mean differences of CD4 counts did not differ significantly between the different ocular disorders . The most prevalent HIV related ocular disorder in this study was retinal microvasculopathy . The mean CD4 count for participants with this disorder was 142 cells/mm3) when compared to those who did not have ocular disorders (309 cells/mm3) (p = 0.012). This mean CD4 count (172 cells/mm3) indicates that the patients who manifested HIV related ocular disorders had severe immune suppression . Also, patients who manifested HIV related ocular disorders recorded significantly higher mean values of viral load copies as compared to their counterparts who did not manifest ocular disorders (p = 0.006). However, no significant association was found between ocular disorders and current CD4 counts (p = 0.10). Participants who had HIV related ocular disorders had significantly lower mean values of nadir CD4 counts . Again, no association was found between ART usage and ocular manifestation .Non-HIV related ocular conditions such as nonneurological blepharoptosis, pingueculae, pterygia, conjunctivitis, cataract, and glaucoma suspects were also found in the study population. Majority  of the participants who had HIV related ocular disorders were at stage two of the disease while 4 and 2 were at stages one and three, respectively. There was, however, no association between ocular manifestation and clinical stage of the disease (Previous studies have always considered the associations between HIV related ocular manifestations and CD4 counts but not viral loads. The current study sought to evaluate the associations between presenting ocular disorders and CD4 counts/viral load copies in HIV positive patients attending the Cape Coast Teaching Hospital, Ghana. The 5.8% prevalence of HIV related ocular disorders in the present study was lower than in a recently published study from the Ashanti region of Ghana where the authors reported ocular complications in 48% . That stThe finding of 9.8% low vision in this study was higher than the 3.1% reported by Abokyi et al.  also in Herpes zoster ophthalmicus as the second most common ocular disorder was comparable with reported cases from Nigeria and Cameroon , 23. Aye3 [3 and majority, 69.5%, were on ART regimen. Spontaneous resolution of CMV retinitis has been reported in patients with increased CD4 count relating to antiretroviral therapy [The finding on CMV retinitis is consistent with that in Ethiopia  and Tanz3 . The ver3 . In the  therapy . Other s therapy , 29. The therapy . These o therapy . The fin therapy . From Ta therapy . While o therapy .Consistent with other findings, our study suggests that ocular manifestations in HIV patients are heightened by reduced CD4 counts and corresponding higher viral load copies. Particularly, CMV retinitis was associated with extremely high viral load copies though it was very rare.


We evaluated the sensitivity and specificity of the WHO immunological criteria for detecting antiretroviral therapy (ART) treatment failure in a cohort of Vietnamese patients. We conducted a stratified analysis to determine the effects of BMI, peer support, adherence to antiretroviral (ARV) drugs, age, and gender on the sensitivity and specificity of the WHO criteria.+ counts to the gold standard of virologic testing as a diagnostic test for ART failure at different time points of 12, 18, and 24 months.We conducted a retrospective cohort study of 605 HIV-infected patients using data previously collected from a cluster randomized control trial study. We compared the sensitivity and specificity of CD4The sensitivity [95% confidence interval (CI)] of the WHO immunological criteria based on a viral load ≥ 1000 copies/mL was 12% (5%-23%), 14% (2%-43%), and 12.5% (2%-38%) at 12, 18, and 24 months, respectively. In the same order, the specificity was 93% (90%-96%), 98% (96%-99%), and 98% (96%-100%). The positive predictive values (PPV) at 12, 18, and 24 months were 22% (9%-40%), 20% (3%-56%), and 29% (4%-71%); the negative predictive values (NPV) at the same time points were 87% (84%-90%), 97% (95%-98%), and 96% (93%-98%). The stratified analysis revealed similar sensitivities and specificities.The sensitivity of the WHO immunological criteria is poor, but the specificity is high. Although testing costs may increase, we recommend that Vietnam and other similar settings adopt viral load testing as the principal method for determining ART failure. Surveillance of HIV antiretroviral therapy failure has been challenging in resource-limited settings. This has resulted in suboptimal identification of treatment failure . In sett+ cell counts, when compared to the gold standard of VL monitoring [Early identification of ART treatment failure allows patients a higher chance of success when switching to a second line ART . Mountinnitoring –14.  adopted the WHO clinical and immunological criteria, described previously, for their guidelines. Despite the addition of routine VL testing every 6 months, the test is only performed in a few select laboratories in large cities like Ha Noi and Ho Chi Minh City , 21, 22.This study sought to determine the sensitivity and specificity of the WHO immunological criteria for identifying ART treatment failure in resource-limited settings. As VL testing is not routinely done in Vietnam, there isn’t much published data on the effectiveness of the Vietnam National Guidelines . This st+ levels, viral load levels, adherence to ARV, gender, BMI, peer support, and age.This retrospective cohort study collected information from HIV-infected patients on first-line ART from a cluster randomized controlled trial carried out in a rural resource-limited setting of Quang Ninh, Vietnam between July 2007 and November 2011 . The incFor the purposes of this analysis, WHO immunologic failure was diagnosed if the participant met one of the following criteria:+ counts that return to or fall below pre-therapy baseline level,CD4+ from the on-treatment peak value after at least 6 months of the initiation of ART,50% decline of CD4+ count <100 cells/μL after a year without any increase [CD4increase , 15.The current Vietnam guidelines for viral load defines treatment failure at viral load > 5000 copies/mL . HoweverWe presented descriptive continuous data as median and interquartile range (IQR) and listed categorical variables as numbers and percentages. We determined the sensitivity and specificity for predicting various definitions of virologic failure mentioned previously at 12, 18, and 24 months after initiation of ART. We determined the positive and negative predictive values of the immunologic failure criteria as well. In addition, we adjusted the diagnostic test analysis with both VL > 5000 copies/mL and VL ≥ 1000 copies/mL, for several variables such as gender, age, BMI, peer support, and adherence to ARV. The results are presented in the tables with the corresponding 95% confidence interval (CI). The confidence intervals were based on formulae provided by Simel et al .2 and above 18 kg/m2. Patients were stratified into groups that have or don’t have peer support. Peer support involved home-based adherence counseling by fellow HIV-infected peer supporters [BMI was stratified between below 18 kg/mpporters . Adherenpporters . The pacpporters .The study was approved by the Institutional Review Boards of Hanoi Medical University, Ministry of Health, Vietnam , the Regional Board for Ethics Review from Karolinska Institutet in Stockholm, Sweden (number 2006/1367-31/4), and the Institutional Review Board (no. Pro00027277) at the University of South Florida.This study included the baseline characteristics of a total of 605 HIV-positive patients . These p+).Among the different definitions, the proportions of ART treatment failure were less than the proportions of NO ART treatment failure. The virologic criterion VL ≥ 1000 copies/mL got the highest proportion of ART treatment failure at different times.As shown in The sensitivity, based on treatment failure at viral load > 5000 copies/mL and the overall WHO immunological criteria 12 months after the start of treatment, was 30% and the specificity was 93%. However, among the people who tested positive for WHO immunological criteria, only 9% actually had treatment failure (the corresponding PPV). For those that tested negative, 98% did not have the treatment failure (NPV).At 18 months, the sensitivity and specificity were 12.5% and 98%, respectively, while the PPV and NPV were 10% and 98%, respectively.On the contrary, at 24 months after treatment initiation, the sensitivity was 22%. The PPV, among patients that tested positive, was 29% that had ART treatment failure. All the indexes are reported in th and 24th months, while at 18 months, it was slightly increased  where patients are only tested if treatment failure is suspected using WHO clinical and immunological criteria , 28, 29.Viral load testing accurately and precisely identifies treatment failure as well as non-adherence . Such an+ levels to detect treatment failure is the inability to determine the functionality of the T cells being produced. If the patient was co-infected with HTLV (Human T-lymphotropic virus), patients’ CD4+ levels could increase, but many of the CD4+ cells may actually be nonfunctional [A major downside of relying on CD4nctional . This conctional .TM Load (a simple reverse transcriptase assay), that have the same efficacy as other, more expensive viral load tests [Historically, there has been resistance to switching to routine viral load testing due to high costs . Howeverad tests .+ tests [+ tests in exchange for viral load testing.Countries, like Uganda, have successfully switched to using solely viral load testing to determine treatment failure . Countri+ tests –41. This+ counts, which could have led to bias in the estimation of immunologic failure. This study did not control for ART treatment during the management of patients. If patients were found to have treatment failure, they were assessed in relation to adherence. If they had good adherence and genotyping showed specific resistance mutations, they were switched to a different treatment regimen. We were also limited to the variables provided in the dataset. For example, the BMI was set at either below and above 18 kg/m2. We couldn’t adjust BMI to the cut off for normal and underweight BMI Click here for additional data file.


While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria.We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted.3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients retained through 84 months maintained ≥95% adherence.Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mmWhile improved access to HIV care and treatment remains a challenge in Nigeria, our study shows that a high quality of care was achieved as evidenced by strong long-term clinical, immunologic and virologic outcomes. The rapid scale-up of global HIV antiretroviral therapy (ART) in resource-constrained settings (RCS) over the past decade has successfully enrolled millions of HIV-infected patients in care and treatment programs . While tNigeria is the most populous country in sub-Saharan Africa with an estimated population of nearly 180 million and current estimated HIV prevalence of 3.2%. Despite a low HIV prevalence, Nigeria has the second highest burden of HIV infection in the world ,14. In 2In 2001, the Federal Government of Nigeria initiated a national ART program as part of its enhanced response for the care and support for HIV-infected persons . The NigBetween 2004–2012, the Harvard/APIN PEPFAR program expanded from 6 to 36 hospitals and clinics, including 9 tertiary referral hospitals, 23 secondary hospitals or primary health clinics, and four non-governmental organizations (NGOs) in 9 of the 36 states of Nigeria . Standardized protocols were developed for clinical management, laboratory testing and pharmacy handling, conforming to an optimized standard of care consistent with Nigerian National ART and PMTCT guidelines. Expanded and renovated clinics, pharmacies and equipped laboratories allowed for the provision of ART to large numbers of patients . ComputeIn this evaluation, we provide data on long-term outcomes of adult patients enrolled in the Harvard/APIN PEPFAR Program between 2004–2012. A main objective of the study was to describe the baseline characteristics of the adult patients treated in the Harvard/APIN PEPFAR program and any changes in baseline characteristics over the 8-year study period. The other major objective of the study was to assess the long-term outcomes of ART, including immunologic and virologic. Additionally, we examined long-term adherence patterns for patients retained on ART.3 or if symptomatic with CD4+ cell counts below 350 cells/mm3; criteria shifted to include CD4+ cell counts below 350 cells/mm3 regardless of symptoms starting in 2010. Written informed consent was obtained from all patients upon initial enrollment; for minors under 18 years of age, written informed consent from the parent/legal guardian and written assent to participate from the minor were dually documented. The protocol and consent forms were reviewed and approved by the Harvard Chan Institutional Review Board (IRB) and the Nigerian Institute for Medical Research IRB, which is a Federal-wide Assurance (FWA)-approved IRB that covers all other Harvard/APIN PEPFAR program sites.The Harvard/APIN PEPFAR adult ART program enrolled patients with documented evidence of HIV infection by rapid test screening and HIV immunoblot confirmation. Since the Government of Nigeria commenced their ART program in 2002, the cohort included patients that might have already had as much as 2 years of previous ART at the time that they were enrolled in the Harvard/APIN PEPFAR program. For ARV-naïve patients, eligibility for ART in the Harvard/APIN PEPFAR program followed the Nigerian National Guidelines ,20, whicWe conducted a retrospective evaluation of the prospectively collected data for patients who were provided routine ART services through the Harvard/APIN PEPFAR Program and consented to participation in future evaluations. The analyses on long-term outcomes included patients who were enrolled on ART between June 2004-February 2012. All patients were at least 15 years of age at enrollment. Patients who had HIV-2 or dual HIV-1/2 infections, or were on a non-standard first-line (1L) ART regimen  were excluded from the long-term outcomes analyses. Additionally, some issues in early viral load (VL) testing procedures and pharmacy documentation issues at two of our sites were discovered; therefore, patients who enrolled at either of those two sites before April 2007 were excluded from the evaluations as some of their early data were not reliable.In early 2000, the production of generic ART drugs was just beginning and formed the basis of many ART programs in developing countries, including Nigeria. At PEPFAR program initiation in Nigeria, the most common 1L ART included stavudine (d4T), lamivudine (3TC), and nevirapine (NVP). In late 2006, the increased recognition of the toxicity and inferior efficacy of regimens containing d4T prompted the revision of international guidelines, with eventual removal of d4T from recommended 1L regimens. In 2003–2005, access to tenofovir (TDF)-based regimens was spreading to RCS, although the cost of the branded version slowed its introduction. In 2008–2009, the introduction of the generic equivalents and the fixed-dose combination (FDC) Atripla, which was a combination of TDF, emtricitabine (FTC), and efavirenz (EFV), expanded usage of TDF. In the Harvard/APIN PEPFAR program, TDF-based regimens were considered for patients with hepatitis B virus (HBV) co-infection and those with anemia; NVP was the NNRTI of choice in women of child bearing potential, due to the teratogenic potential of EFV; and, in cases of TB-HIV co-infection, patients were switched to EFV at higher dosing of 600 or 800 mg/day.Patient samples were drawn for laboratory testing at baseline, 6 months post-initiation of ART and every 6 months thereafter, regardless of prior treatment status. Laboratory tests included automated hematology, clinical chemistries, CD4+ cell counts by flow cytometry , and plasma VLs using the COBAS® Amplicor version 1.5 . Hematology consisted of a complete blood count and clinical chemistries. Additional chemistry evaluations could be requested based on the physician’s discretion. Serology for HBV  and hepatitis C virus (HCV)  infections was conducted at baseline. All patients were evaluated for tuberculosis (TB) using sputum and/or chest radiograph at baseline and at all subsequent clinical visits if suspected clinically . PatientFrom the start of the Harvard/APIN PEPFAR program, all patient demographic, clinical and laboratory data were electronically captured using a Harvard Chan School-designed FileMaker Pro  electronic medical record system (EMRS) . Data foWe evaluated baseline demographic  and clinical , CD4+ cell count, VL and anemia) factors, where baseline was defined as the time of ART initiation. Baseline clinical assessments or laboratory evaluations for naïve patients were the closest measurements to, and up to six months before or 0.5 month after, their first ART pick-up date.2), normal (18.5–24.9 kg/m2), overweight (≥25.0). Anemia was defined using WHO-recommended hemoglobin cut-offs: non-anemia (≥12 g/dL for women and ≥13 g/dL for men), mild/moderate anemia (8–11.9 g/dL for women and 8–12.9 g/dL for men), and severe anemia . VL at baseline was stratified into three categories . Virologic suppression was defined as a single viral load that was below the limit of detection (≤400 copies/mL). Using pharmacy prescription electronic refill records, which have been shown to be a valid proxy [For analyses, age was converted to a categorical variable based on quartiles and occupation was collapsed into non-income generating  and income generating  categories. Clinical variables were collapsed into categories based on relevant thresholds for the regression. BMI was grouped into three WHO-defined categories: underweight  if they had missed the last scheduled appointment by more than two months by the time of database closure. Patients for whom death, withdrawal, or transfer to non-Harvard/APIN sites was recorded during the period of evaluation were not considered LTFU. Data on deaths, withdrawals, or transfers were passively obtained when either patients or their acquaintances provided the information; active tracing of patients that were late to appointments was not feasible as part of the program.3 after 6 months of treatment; 2) CD4+ count below baseline level after 6 months of treatment; and/or, 3) CD4+ count less than 50% of peak on treatment level. Patients that were switched to 2L ART were also considered virologic and immunologic failures. Patients for whom an alternate 1L regimen was substituted due to toxicity, stock-outs of certain medications, or other related issues were still considered to be on 1L and were not included in the failure categories.Virologic failure (VF) was evaluated only for patients on ART ≥5.5 months (to provide window of time to include VLs close to month 6) and with ≥2 VLs after 6 months, and was defined as two consecutive VLs after 6 months on ART, which surpassed 1,000 copies/mL. Immunologic failure (IF) was evaluated for patients on ART ≥5.5 months and with ≥1 CD4+ cell count after 6 months and was defined using the following criteria: 1) CD4+ count <100 cells/mmΧ2 test. A non-parametric test for trend was utilized for examining patterns in baseline CD4+ cell counts by enrollment year. Statistical significance was defined at an α-level of 0.05.Baseline demographics and clinical characteristics were measured using standard descriptive statistical methods. Bivariate comparisons of categorical variables were performed using the Kaplan-Meier survival analyses were used to estimate the time from the initiation of ART to two different major outcomes: 1) virologic failure; and, 2) immunologic failure. For patients who did not reach the endpoint, the data were censored at the date of the last visit. The log-rank test was used to compare survival times between strata for categorical variables. All predictors that were significant at the p<0.20 level in bivariate methods were further evaluated in a random effects Cox proportional hazards model, which accounted for heterogeneity between sites and was fitted using backward elimination. Additionally, we incorporated time-dependent factors into the analyses, including BMI, CD4+ cell count, VL, anemia status, and average percent adherence, which were measured every six months. VF during a given time period was assessed for associations with time-dependent factors measured during the previous time period. Since VF is defined as occurring at the first of two consecutive VLs >1000 cp/mL, any recorded VL during the time period immediately preceding VF would generally be suppressed; therefore, in the VF analysis only, we assessed unsuppressed VL during the current time period as a time-dependent predictor of VF, i.e., of a second consecutive unsuppressed VL. To address potential bias due to patients who were excluded because of missing data, multiple imputation of missing values was performed, following exploration of pattern of missigness and verification that data were missing at random, using chained equations assuming missing at random and 10 imputed data sets. Values for the Cox models were generated using both complete cases and multiply imputed data.All statistical analyses were conducted using Stata version 13.1 .From June 2004 through February 2012, 99,887 adult patients were enrolled in the Harvard/APIN PEPFAR Program; of those patients, 91,083 were mono-infected with HIV-1 and had reliably collected data in the program EMRS. Within that subset, 86,471 initiated standard 1L regimens with 70,002 (81.0%) of those patients ARV-naïve and 16,469 (19.0%) with previous ARV experience at initiation in the Harvard/APIN PEPFAR program . The medCollectively, these 70,002 patients represent 136,852  person-years (PY) on ART. Amongst the ARV-naïve patients enrolled on one of the standard 1L regimens, the majority were women (65.2%). The median age at entry was 35 years (IQR: 29–41), and was higher for males, at 39 years (IQR: 33–45), than for females, at 32 years  for d4T+3TC+EFV; 50.6  for d4T+3TC+NVP; 24.0 months  for AZT+3TC+EFV; 19.3 months  for AZT+3TC+NVP; 12.0 months  for TDF+3TC/FTC+EFV; and, 16.3 months  for TDF+3TC/FTC+NVP  and the median baseline HIV RNA load was 71,310 copies/mL . Evaluation of baseline CD4+ cell count and WHO stage by enrollment year revealed an overall increasing trend in median baseline CD4+ cell counts between 2004–2012  had a documented WHO Stage at ART initiation, of which more than half were asymptomatic or relatively free of symptoms  meeting the WHO Stage I or II definition. Amongst the naïve patients, 10.2% were HBV-positive, 3.6% had documentation of HCV, 8.9% had evidence of severe anemia, and 20.4% had TB at time of ART initiation. Laboratory measurements indicated that the median baseline CD4+ cell count was 149 cells/mm3 (IQR: 78 – 220) at ART initiation to 487 cells/mm3 (IQR: 343–666) at 72 months, after which it appeared to plateau ; the value differed by baseline CD4+ cell count: 120 cells/mm3 (IQR: 63–196) for patients with a baseline CD4+ cell count ≤100 cells/mm3 as compared to 140 cells/mm3 (IQR: 59–240) for those with baseline 101–200 cells/mm3 and  and had VL measured at month 6 post-initiation , 69.3%  were considered to have achieved early viral suppression . Of the patients that failed to achieve early viral suppression, an additional 14,233 of the patients with subsequent VL data eventually suppressed VL, resulting in an overall 85.4%  that achieved viral suppression ever. Using a longitudinal view, suppression rates for the study population gradually increased to 75.0% at 42 months and appeared to plateau through to month 84 . Using a3, 65.4% were suppressed at month 6 and 72.3% by month 12. Comparatively, for those starting at 101–200 cells/mm3, 70.7% were suppressed by month 6 and 77.0% by month 12, and for those starting at 201–350 cells/mm3, 73.3% were suppressed at month 6 and 79.3% by month 12. Interestingly, after CD4+ cell counts of 350 cells/mm3, we saw a declining trend as the baseline CD4+ cell counts increased, where of those with 351–500 cells/mm3, 71.5% were suppressed at month 6 and 78.5% by month 12 and of those with >500 cells/mm3 at baseline, only 64.6% were suppressed at month 6 and 73.0% by month 12  patients met criteria for failure resulting in an overall VF rate of 96.5 cases per 1000 PY . The median time to VF was 11.6 months (IQR: 7.6–19.8) and rate of VF was highest at month 6 at 306.0 cases per 1000 PY , then decreased to 30.9 cases per 1000 PY  at month 42 at which point it appeared to plateau . Of the In bivariate analyses, age, education, employment status, marital status, ART regimen, ART enrollment year, site type, WHO stage, BMI, CD4+ cell count, HBV and HCV status, VL, anemic state, adherence were all found to be predictors of VF . FollowiSimilar to VF, the strongest predictors of IF in the adjusted model with multiply imputed data were lower CD4+ cell count and unsuppressed VL at previous visit, and poorer adherence. Lower BMI and anemia at previous visit were also predictive of IF. In measuring IF, female sex was slightly protective as was being married (versus single). Patients on NVP-containing regimens paired with TDF or d4T also appeared to be at a slightly higher risk for IF as compared to those on TDF+EFV. Unlike what was seen for VF, higher baseline CD4+ cell counts and later enrollment year were associated with higher risk for IF in both complete case and multiple imputation adjusted Cox regression models.We were able to examine long-term adherence patterns for patients that were retained as long as 84 months post-initiation of ART, with over 5,500 people on ART for over 5 years. We found that for those that remained in the program or had sufficient years of follow-up time since enrollment, the majority exhibited very strong  adherence for many years .To examine if adherence patterns appear different in patients that were retained long-term versus those that eventually discontinued treatment, we compared the median percent adherence for each 6-month time interval up to month 36 post-initiation of ART for patients who were retained on ART versus those that eventually transferred, died, withdrew or were lost to follow-up. For those that were retained or transferred to another site, the median percent adherence was above 95% during 0–6 months and rose to 100%. For those that eventually died, median adherence also started above 95%, but dropped gradually over time on ART and rose again in those that died closer to 30 months. Finally, for patients that were eventually LTFU or withdrew, median percent adherence began at 88.5% and never rose above 95% during the observation period . We also3, 63.3% had an average adherence of ≥95% during their first 6 months, where adherence patterns were not significantly different when CD4+ cell count groups were further stratified into ≤100 cells/mm3, 101–200 cells/mm3, and 201–350 cells/mm3 categories . We found that of the patients with baseline CD4+ cell counts ≤350 cells/mmp<0.001; .In this evaluation, we examined long-term outcomes for a large cohort of adult patients enrolled in the Harvard/APIN PEPFAR program in Nigeria between the years 2004–2012. As a part of these evaluations, we examined longitudinal patterns in ART regimen prescription patterns, long-term immunologic and virologic outcomes, adherence patterns, and continuous predictors of treatment failure. Overall, we report strong long-term outcomes, consistent with data from earlier short- and medium-term evaluations from other international scale-up programs in South Africa, Ethiopia, Uganda, Botswana, Senegal and China ,9,31,32.In the past decade, the recommended drugs and regimens for optimal ART were changing worldwide. The patents for many of the early antiretrovirals (ARVs) were expiring and many generic versions were being manufactured in India, Thailand, Brazil, and elsewhere. In addition to less expensive versions of these drugs, FDCs were made available to reduce the pill burden and improve adherence. The PEPFAR program provided important assistance in expediting the U.S. Food and Drug Administration review and approval of these drugs . As a re3, we hypothesized that the baseline clinical characteristics of newly enrolled patients changed over the enrollment years. As expected, this study revealed higher baseline CD4+ cell counts and greater proportion of patients enrolling at lower WHO stages in the program from 2004–2012. As the years passed, and the sicker patients enrolled on ART during the early years of the program, the patients enrolled in later years typically were initiated at higher baseline CD4+ cell counts. Of note, in 2013, the WHO recommended that ART should be initiated in all individuals with a CD4 count >350 and ≤500 cells/mm3. Additional evaluations on data beyond 2013 would be expected to reveal even higher median CD4+ cell counts.Despite the low variety in types of ARVs, as the general availability of ART rapidly increased with scale-up of PEPFAR and Global Fund supported programs and the WHO recommendations for initiating ART evolved over these years, increasing CD4 count criteria from 200 to 350 cells/mmWhile the enrolled patient population started with relatively low median CD4+ cell counts at ART initiation, the rate of immune recovery was strong up through 84 months of follow-up. Viral suppression rates were also high out to 84 months of follow-up, mimicking the findings from some recent, smaller middle- and long-term outcome analyses conducted in Botswana, South Africa, Senegal, and Uganda ,32,34.et al., from British Columbian, Canada, indicated that patients that started ART with CD4+ cell counts of at least 500 cells/mm3 were more likely to be virally suppressed at 9 months post-initiation that than those with lower starting CD4+ cell counts [3 were more likely than those with lower and higher baseline CD4+ cell counts to be suppressed at both month 6 and month 12 post-initiation of ART. From a clinical perspective, it makes sense that patients starting with the lower CD4+ cell counts would need more time to achieve viral suppression. However, for the groups starting with higher CD4+ cell counts, it is possible that they were feeling well at the time they started medication and perceived a lower benefit to taking all of their medications or maintaining a high level of adherence. Interestingly, we also found that early average adherence was lower for those with baseline CD4+ cell counts >350 cells/mm3 as compared to those patients with counts ≤350 cells/mm3. Furthermore, we found a higher relative hazard of virologic failure for patients with baseline CD4 >350 cells/mm3 compared with those with baseline CD4 of 201–350 cells/mm3. This finding is consistent with those of Grimsrud et al, who found that patients with baseline CD4 counts≥300 cells/μL were more likely to be LTFU after 24 months on ART than those patients with CD4 counts of 150–199 μL [A study by Lima l counts . In our et. al. showed that patients who initiated ART on TDF in combination with NVP had higher risk of VF than patients who initiated on AZT with NVP in our program [The regular measurement of VLs was a unique feature of our program, allowing for assessment of VF, the most objective determination of ART outcome as would be measured in resource-rich settings. The baseline risk factors for VF we found  and the time-updated risk factors  should be useful in identifying higher risk patients for targeted adherence counseling and monitoring strategies. While one recent study of long-term outcomes in Cameroon showed increased risk for VF in males versus females , in our  program , which o program . Our fin program , and are program .Interestingly, unlike for VF, higher baseline CD4+ cell counts were associated with IF; this may be because those with higher baseline CD4+ cell counts are more likely to have their CD4+ cell count drop below baseline, one of the criteria for immunologic failure, during ART than those with already low baseline levels. This may also explain why later enrollment year was also weakly associated with higher risk of immunologic failure as the baseline CD4+ cell count criteria for ART enrollment increased in 2010.Just as our previous evaluation showed that the largest percentage of patient LTFU occurred during the first 12–18 months of ART , we founBecause we had both VF and IF data, we were able to examine accuracy of IF criteria to predict VF in a large cohort of patients. Similar to the earlier study by Rawizza et al. , but nowOur study also demonstrated strong long-term adherence, similar to what was found in a smaller, middle-term ART cohort study from Botswana , furtherThis evaluation does have some limitations. As a retrospective observational cohort study, this analysis was limited by missing data, which was expected considering the rapid scale-up of the program and data collection in the context of routine care. While we attempted to control for some of the missing data issues through use of multiple imputation methods, it is possible that patients who were missing certain time-updated clinical laboratory values may have been more likely to develop failure than those who were not missing data, which may have affected the imputation results and the magnitudes of association in the multivariate models. The study was limited because the program did not actively trace all patients that were lost, which likely resulted in an overestimation of LTFU and underestimation of mortality, transfers and withdrawals as has been indicated in previous other studies in which LTFU patients were traced –47. The This evaluation also has notable strengths. The large enrollment of the program and lengthy follow-up provide statistical strength to reinforce our findings. To our knowledge, other large cohorts examining ART outcomes include one from Botswana, which described medium-term outcomes for over 126,000 patients  and anotThe United Nations Sustainable Development Goals (SDGs) aims to see an end to the HIV/AIDS epidemic by 2030. While access to ART rose dramatically between 2004 to 2014 as a result of major contributions from the massive scale-up programs supported by PEPFAR, the Global Fund for Tuberculosis, AIDS and Malaria, the World Bank, the Clinton Foundation, it was estimated in 2013 that only 20% of patients in Nigeria that required ART were actually receiving it [


Background: Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as first-line ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting.Patients and methods: A retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay .Results: At 96 weeks, extensive TAMs (≥3 mutations) were present in 50% and 73% of nevirapine- and abacavir-treated patients, respectively. The mean (SE) number of TAMs accumulating between week 48 and week 96 was 1.50 (0.37) in nevirapine-treated participants and 1.82 (0.26) in abacavir-treated participants. Overall, zidovudine susceptibility of viruses was reduced between week 48 [geometric mean fold change (FC) 1.3] and week 96 . There was a small reduction in tenofovir susceptibility .Conclusions: Ongoing viral failure with zidovudine-containing first-line ART is associated with rapidly increasing drug resistance that could be mitigated with effective viral load monitoring. After 24 weeks, participants continued to receive the study drugs open-label and were followed up as part of DART. Of those randomized, 32 died before week 96, and 21 were lost to follow-up. A further 107 participants with CD4 counts ≥300 cells/mm3 at weeks 48 or 72 after ART initiation were randomized to structured treatment interruption (STI) with up to four repeated cycles of 12 weeks on/off therapy and are excluded. In addition, 7  participants had switched to lopinavir-based second-line ART by week 96, leaving 433 participants , for whom 96.7% of week 48 and week 96 HIV-1 RNA measurements were available.DART-NORA enrolled 600 previously untreated and asymptomatic Ugandan patients with CD4 counts of <200 cells/mmpol, with identification of resistance mutations according to the latest IAS-USA list,t-tests and linear regression as appropriate. All P values were two-sided. All analyses were performed using STATA v. 14.0 .Viral loads were measured using Roche Amplicor 1.5. Genotypic resistance testing was by standard population sequencing of Ethics approval both for DART and the NORA sub-study was obtained both in Uganda [Uganda Research Unit on AIDS (UVRI) Science and Ethics Committee] and the UK .3.Fifty-one of 433 12%) participants were identified as having a viral load >1000 copies/mL at both week 48 and week 96 , mean (SD) viral load was 4.67 (0.49) log10 copies/mL at week 48 and 4.52 (0.55) log10 copies/mL at week 96 [mean decrease of 0.15 log10 copies/mL (95% CI −0.06–0.36)]. In those randomized to abacavir (n = 22), the mean viral load was 4.13 (0.72) log10 copies/mL at week 48 and 4.50 (0.66) log10 copies/mL at week 96 [mean increase of 0.37 log10 copies/mL (95% CI 0.10–0.64)].The relationship between an individual’s viral load at weeks 48 and 96 is shown in Figure P = 0.38), although numbers in each group were small.Overall, the prevalence of each TAM increased between weeks 48 and 96 in our sample of 36 patients [mean absolute increase 25% range 19%–31%)]. TAMs at position 215 were particularly frequent (>70% in each arm) followed by D67N (Table 9%–31%]. P = 0.01)   between these timepoints  1.3] and week 96  Figure . Similar) Figure  with moss Figure .Figure JAC Online). The abacavir-selected mutation L74V mutation was not observed in any participant (Table S1).Lamivudine resistance M184V) was present in all patients with viral failure at 96 weeks except one participant on the nevirapine arm , and both participants without NNRTI mutations at week 48 went on to develop G190A by week 96.NNRTI-based cART appears to be associated with rapid accumulation of TAMs in those with virological failure (1.50 TAMs per year for zidovudine/lamivudine/nevirapine-treated patients) in this resource-limited setting where routine viral load monitoring is not performed. We observed that abacavir/zidovudine/lamivudine also resulted in rapid TAM accumulation (1.82 TAMs per year), although WHO guidelines do not currently recommend triple nucleoside-based cART for first-line cART. Our estimate of TAM accumulation for NNRTI-based ART is higher than reported previously in South African adultsOver half of all patients with viral failure by week 48 in this study had ≥3 TAMs in total by week 96. Accumulated TAMs were associated with reduced phenotypic drug susceptibility amongst a smaller sample of patients, with zidovudine susceptibility significantly falling between weeks 48 and 96, and a small non-significant decrease observed for tenofovir.We know from previous studies that boosted PI-based first-line ART is protective against the development of NRTI mutations, in comparison with NNRTI-based first-line therapy.This study was limited by a relatively small number of available phenotype pairs and the conclusions are largely drawn from genotypic information. Furthermore the data are derived from nevirapine-treated patients and efavirenz is now the most widely used NNRTI in resource-limited settings.,Despite its associated toxicity, zidovudine has emerged as an important component of cART regimens in resource-limited settings; moreover, dose reduction reduces incidence of moderate to severe anaemia.,Transmission of NRTI drug resistance compromises subsequent response to first-line therapies,Effective viral load monitoring has been identified as a priority areaSupplementary DataClick here for additional data file.


The 2011 World Health Organization global report on HIV and/or AIDS estimated that sub-Saharan Africa comprised 67% of the global HIV burden, with a current estimate of 5.9 million cases in South Africa. Since the introduction of antiretroviral therapy, there has been an increase in the incidence of non-AIDS-defining cancers. Gestational trophoblastic neoplasm (GTN) is a rare pregnancy-related disorder with an incidence ranging from 0.12–0.7/1000 pregnancies in Western nations. The overall cure rate is about 90%. Response to treatment for GTN is generally favourable; but the sequelae of HIV and/or AIDS, the resultant low CD4 counts, comorbidities, poor performance status and the extent of metastatic disease in patients receiving chemotherapy, compromise the prognosis and survival. No clearly established association between HIV and/or AIDS and gestational trophoblastic neoplasm (GTN) exists. Data from the Swiss HIV Cohort Study showed that 19% of all cohort deaths in the ART area were attributable to NADCs.4Kaposi’s sarcoma (KS), non-Hodgkin’s lymphoma (NHL) and cervical cancer are the most observed AIDS-defining cancers. In the era of ART, a significant decrease in the incidence of AIDS-defining illnesses has been observed, whilst non-AIDS cancers (NADCs) are on the increase. An estimated 30% – 40% of HIV-infected patients are likely to develop a cancer during the duration of their disease.6 The occurrence of malignancy amongst people living with HIV and/or AIDS represents a management challenge. We present here two choriocarcinoma case studies of women with HIV and/or AIDS.GTN is a rare pregnancy-related disorder that derives from placental tissue and is clinically diagnosed if the B-HCG level fails to decrease or normalise in women when a normal pregnancy is excluded, and collectively includes: invasive mole, choriocarcinoma and placental site trophoblastic tumour (PSTT) that can lead to death if left untreated. Potential risk factors for the development of GTN include a history of a previous molar pregnancy, partial mole (0.5% risk) and a complete mole (15% risk), maternal age and a post-evacuation, persistent raised B-HCG level. Management includes careful dilatation and curettage (D&C), and the need for systemic treatment is guided by the International Federation of Gynecology and Obstetrics (FIGO)/WHO score that predicts if either single agent or combination chemotherapy is required. GTN is now one of the most curable solid tumours, with cure rates of more than 90% even in the presence of metastatic disease.The Human Research Ethics Committee (HREC) of Stellenbosch University approved the present report.A 33-year-old woman  presented post-evacuation for a miscarriage with persistent vaginal bleeding and a raised B-HCG value. She was living with HIV and/or AIDS and had been established on ART for one year. Clinical examination confirmed an abdominal uterine mass of 22 weeks’ gestation with a foul-smelling vaginal discharge. Staging examinations included a computed tomography (CT) scan of the lungs, abdomen and pelvis and confirmed several bilateral lung metastases and an extensive tumour that involved the uterus and extended into the anterior abdominal wall . Abnorma9/L (4.00–10.00 ×109/L), haemoglobin 6.6 g%, and platelets 15 ×9/L). A follow-up CD4 count decreased to 29 cells/μL and the B-HCG value decreased to 50 296 IU/L. Supportive management included granulocyte-stimulating factor (G-CSF) and intravenous antibiotics according to the sensitivity of a positive blood culture (Klebsiella pneumonia). A vaginal pus swab cultured Candida species.Management included continuation with ART , intravenous antibiotics (piperacillin and amikacin), and low-dose chemotherapy with the alternating regime of methotrexate 50 mg alternative days  with leucovorin rescue. She completed one cycle without any adverse effects. However, a week post-chemotherapy she developed a neutropaenic fever. Abnormal laboratory studies then confirmed serum-creatinine 10.7 mmol/L (2.1 mmol/L – 7.1 mmol/L), urea 151 μmol/L (49 μmol/L – 90 μmol/L), and a pancytopaenia: white blood cells 0.13 × 10The outcome for the patient was unfortunate as she died owing to severe neutropaenic sepsis from a resistant Klebsiella and Candida sepsis that resulted in acute renal failure and severe immune suppression.A 20-year-old woman  presented with a history of haemoptysis, grade IV dyspnoea and a raised B-HCG level. She was known to have had a previous molar pregnancy, diagnosed three years previously. On clinical examination, symptoms and signs of thyrotoxicosis were present. Staging examinations included a lung CT that confirmed numerous bilateral, diffuse soft-tissue nodules throughout both lung fields in keeping with metastatic disease . AbnormaPneumocystis jiroveci prophylaxis (PCP) as her CD4+ count was ≤200 cells/μL, intravenous antibiotic (clindamycin) and acute thyrotoxicosis therapy consisting of carbimazole and propranolol. Low-dose chemotherapy with methotrexate 50 mg alternated with leucovorin rescue on days 1, 3, 5 and 7 was initiated. However, she required admission into a high-care facility when spontaneous breathing became problematic and a continuous positive airway pressure (CPAP) support system was needed. A standard blood culture confirmed Gram-positive cocci and a coagulase negative staphylococcal organism was isolated sensitive to vancomycin. A urine specimen cultured positive for Candida albicans.Management included commencement with ART  with the addition of trimetroprim-sulfamethoxazole for When severe oxygen decompensation occurred, she was admitted to the ICU facility and intubation was necessitated. She died secondary to poor performance status, severe immune suppression, metastatic choriocarcinoma and a Staphylococcus and Candida sepsis when she developed acute respiratory distress syndrome (ARDS).7Malignancy tends to occur at a younger age in people living with HIV and/or AIDS, and presents with atypical presentations, widespread metastatic disease, and aggressive tumour behaviour. In patients with immunodeficiency, physiological principles for the development of malignancy exist: (1) the lack of autoimmune surveillance, (2) an imbalance between cellular differentiation and proliferation and (3) a repeat antigenic stimulation by an oncogenic virus leads to the emergence and proliferation of abnormal cells. Amongst HIV-infected individuals, a 30% – 40% increase in the incidence of NADCs has been observed, and this contributes to morbidity and mortality in HIV-infected patients, now that survival is prolonged with the use of ART.6Established chemotherapy regimens have resulted in a favourable response to GTN, and more than 90% of cases will be cured. Choriocarcinoma is generally associated with pregnancy but an estimated 25% occur after miscarriage, 25% after term pregnancy and the rest after a molar pregnancy. Choriocarcinoma is an aggressive form of GTN owing to its rapid growth and metastatic potential. In women, a high index of suspicion is needed to make a diagnosis based on an unexplained high B-HCG level in the presence of metastases in the lung, liver or brain. A high HCG level can also cause thyrotoxicosis. Delay in diagnosis with delay in starting chemotherapy treatment is a common cause of early death in patients with metastasis.9Using the WHO/FIGO scoring system, patients are grouped into low- and high-risk categories. High-risk patients require combination chemotherapy as they are unlikely to be cured with a single agent. In high-risk patients, 50% of deaths occur within the first four weeks of initial treatment. Early deaths are attributed to respiratory compromise, haemorrhage secondary to a heavy tumour burden within the thorax, and rapid tumour destruction associated with full-dose chemotherapy treatment. Intubation in patients with very poor respiratory function should be avoided as far as possible as high ventilator pressures might trigger fatal intrapulmonary haemorrhage owing to friable tumour vasculature; and hence the introduction of low-dose therapy in the initial treatment of high-risk patients to gradually reduce tumour volume and significantly reduce the risk of haemorrhage to minimise the risk of early death.Because of extensive comorbidities, low-CD4 counts, poor performance status and the extent of metastatic disease, both our patients were offered initial low-dose chemotherapy to debulk tumour load. In the first case study, our patient developed post-chemotherapy neutropaenic sepsis. The outcome for her resulted in death secondary to a poor performance, severe immune suppression (CD4 count decrease from 290 cells/μL to 29 cells/μL), neutropaenic sepsis and extensive metastatic choriocarcinoma that resulted in acute renal failure. In the second case, the patient experienced severe oxygen desaturation owing to extensive lung metastases that necessitated intubation and ICU admission. The outcome for her was dismal as she died secondary to a poor performance status, severe immune suppression, sepsis and extensive metastatic choriocarcinoma when she developed ARDS.11Both our patients experienced severe immune suppression, had extensive metastatic disease and developed associated post-chemotherapy neutropaenia that increased their susceptibility to developing severe and fatal infections. Our cases also highlight previous findings of reported studies on GTN and HIV that confirm an associated poor outcome related to chemotherapy in women with HIV and/or AIDS if they present with low CD4 counts, have a poor performance status and an associated poor tolerance to chemotherapy treatment.Response to GTN is generally favourable with cure rates in excess of 90%. However, in patients with advanced immune suppression, medical management of non-AIDS-defining cancers can be compromised owing to their extent and aggressive tumour behaviour with associated treatment-related complications.


This study assessed how well body mass index .Among 948 patients eligible for analysis, 15.7% (149/948) were underweight (< 18.50), 55.9% (530/948) had normal BMI (≥18.50–24.90), 18.7% (177/948) were overweight (25.00–29.00) and 9.7% (92/948) were obese (≥30.00). Irrespective of TB status, underweight patients, had significantly higher risk of death compared to those with normal BMI at baseline  contains supplementary material, which is available to authorized users. Please see Additional file + count ) 8.8 to 18 months, a total of 56 deaths occurred over 974.2 person-years of follow-up. Underweight patients had higher overall mortality rates of 13.0   , and 29.50 kg/m2 among females (vs. a world average of 24.1 kg/m2) [In the study by Forouzanfar et al. the proportion of females was 4-fold higher compared to males in the > 30.00 BMI group . In 2008+ counts and BMI, as the range of CD4+ counts in our study was small due to the ART eligibility criteria. We do however show that CD4+ count was not an independent predictor of mortality.We could not demonstrate an association between CD4+ > 220 cells/mm3, overall mortality rates were low, despite a baseline BMI of < 18.50 in approximately 40% of patients [+ count gains found that baseline BMI predicted change in CD4+ count after week 96. Relative to men with normal BMI, overweight and obese men had higher CD4+ count increases. It is clear from these studies that low baseline BMI together with low CD4 counts predict mortality, while high BMI is associated with larger CD4+ counts increases, the latter only due to the impact of ART [In a study conducted in four sub-Saharan countries investigating timing of ART in TB-HIV co-infected patients with CD4patients . A studyt of ART .Criteria used to clinically stage HIV disease, and diagnose AIDS defining illnesses, are internationally accepted but are often difficult to apply in resource-poor environments, as they require sophisticated and expensive investigations to make definitive diagnoses . FurtherWe acknowledge several limitations of the study. Data used in this analysis was routinely collected programmatic data, which was flawed by missing data variables on height and weight, reducing our analysable sample. Autopsies are not routinely performed for HIV infected patients that demise. Autopsy data would have improved our understanding of the causes of mortality by the different BMI categories. While we see similar mortality rates among obese patients compared to those with a BMI between 18.50–29.90, these findings need further evaluation given the very small sample size in the obese category. Furthermore, we followed-up patients for 18 months only. Longer follow-up may have provided valuable information on BMI changes following chronic ART, and a further understanding of BMI category on risk of non-communicable disease in clade C HIV infected patients.+ count, or HIV type. Further prospective studies are indicated to evaluate whether BMI could be used to inform intervention decisions, including decisions of when to refer patients for diagnostic work-up or admission.BMI is associated with mortality in HIV infected patients initiating ART and is regarded as an affordable, low-technology, prognostic indicator; independent of age, sex, CD4Additional file 1:Multilingual abstracts in the five official working languages of the United Nations. (PDF 443 kb)