Rational design of an essential diagnostics network to support Universal Health Coverage: a modeling analysis.

BACKGROUND: Diagnostic investigations, including pathology and laboratory medicine (PALM) and radiology, have been largely absent from international strategies such as the Sustainable Development Goals. Further, there is little international guidance on which health system tiers different diagnostics should be placed, a critical step in developing a country-level diagnostics network. We describe a modeling strategy to produce tier-specific diagnostic recommendations based on disease burden, current treatment pathways, and existing infrastructure in a country. METHODS: The relational model assumes that diagnostics should be available at the lowest tier where patients might receive medical management. Using Ghana as an exemplar, the 20 diseases forecasted by 2030 and 2040 to cause the greatest burden in low- and middle-income countries were mapped to three generalized tiers in the Ghanaian health system (Primary, Secondary, and Tertiary care) for three levels of each disease (triage, uncomplicated, and complicated). The lowest tier at which a diagnostic could potentially be placed was restricted by existing infrastructure, though placement still required there be a medical justification for the diagnostic at that tier. RESULTS: The model recommended 111 unique diagnostic investigations with 17 at Primary tier, an additional 45 at Secondary tier and a further 49 at Tertiary tier. Estimated capital costs were $8,330 at Primary tier and between $571,000 to $777,000 at Secondary tier. Twenty-eight different laboratory tests were recommended as send-outs from Primary to Secondary tier, and twelve as send-outs to Tertiary tier. CONCLUSIONS: This model provides a transparent framework within which countries can customize diagnostic planning to local disease priorities, health system patient treatment pathways, and infrastructural limitations to best support Universal Health Coverage.

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study.

BACKGROUND: We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples. Patients received ART at three Nigerian treatment centres. Plasma samples stored when they were in VF were genotyped. RESULT: Of 126 patients with samples available, 57 were successfully genotyped. From ART initiation, the proportion of patients with adherence ≥90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. Sixteen (28%) patients had at least one DRM. Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. Ten patients had resistance to their 1 L drug(s) and six were fully susceptible to the three drugs in the recommended second-line regimen. CONCLUSION: This cohort had little drug resistance mutations. We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance.

Distinct Pattern of Thymidine Analogue Mutations with K65R in Patients Failing Tenofovir-Based Antiretroviral Therapy.

Historically, in HIV patients, the K65R mutation and thymidine analogue mutations (TAMs) have been reported to rarely coexist. We retrospectively reviewed genotype data from paired samples in a cohort of HIV-1-infected Nigerian patients failing first-line antiretroviral therapies containing zidovudine (AZT) or tenofovir (TDF). Samples for each patient were taken at initial confirmed virological failure ≥1000 copies/ml (S1) and then at the latest available sample with viral load ≥1000 copies/ml before switch to second line (S2). Among 103 patients failing AZT, 19 (18.4%) had TAM-1s, 29 (28.2%) TAM-2s, and 21 (20.4%) mixed TAMs by S2. In contrast, in the 87 patients failing TDF, drug resistance mutations at S2 included K65R in 56 (64.4%), TAM-1s in 1 (1.1%), and TAM-2s in 25 patients (28.7%). Interestingly, 30.4% of patients with K65R in our study developed TAMs. These were exclusively K219E ± D67N and were not predicted to confer a resistance cost to future AZT-containing regimens.

Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options.

BACKGROUND: Although there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring. METHODS: Paired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University's HIVdb program. RESULTS: Sequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0-6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with >6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF. CONCLUSIONS: In the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.

Whole-genome sequencing illuminates the evolution and spread of multidrug-resistant tuberculosis in Southwest Nigeria.

Nigeria has an emerging problem with multidrug-resistant tuberculosis (MDR-TB). Whole-genome sequencing was used to understand the epidemiology of tuberculosis and genetics of multi-drug resistance among patients from two tertiary referral centers in Southwest Nigeria. In line with previous molecular epidemiology studies, most isolates of Mycobacterium tuberculosis from this dataset belonged to the Cameroon clade within the Euro-American lineage. Phylogenetic analysis showed this clade was undergoing clonal expansion in this region, and suggests that it was involved in community transmission of sensitive and multidrug-resistant tuberculosis. Five patients enrolled for retreatment were infected with pre-extensively drug resistant (pre-XDR) due to fluoroquinolone resistance in isolates from the Cameroon clade. In all five cases resistance was conferred through a mutation in the gyrA gene. In some patients, genomic changes occurred in bacterial isolates during the course of treatment that potentially led to decreased drug susceptibility. We conclude that inter-patient transmission of resistant isolates, principally from the Cameroon clade, contributes to the spread of MDR-TB in this setting, underscoring the urgent need to curb the spread of multi-drug resistance in this region.

The emerging threat of pre-extensively drug-resistant tuberculosis in West Africa: preparing for large-scale tuberculosis research and drug resistance surveillance.

BACKGROUND: Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. METHODS: Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009-2013 and tested for first- and second-line drug resistance. RESULTS: From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. CONCLUSIONS: West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa.

Potential for false-positive HIV test results using rapid HIV testing algorithms.

Background: In order to scale up access to HIV counselling and testing in Nigeria, an HIV diagnostic algorithm based on rapid testing was adopted. However, there was the need to further evaluate the testing strategy in order to better assess its performance, because of the potential for false positivity. Objectives: The objective of this study was to compare positive HIV test results obtained from the approved rapid testing algorithm with results from western blot tests performed on samples from the same patient. Methodology: A retrospective review was conducted of HIV screening and confirmatory results for patients seen between 2007 and 2008. Rapid test and western blot results were extracted and compared for concordance. Discordant results were further reviewed using a combination of HIV-1 RNA viral load and CD4+ cell count test results and clinical presentation from medical records. Results: Analysis of 2228 western blot results showed that 98.3% (n = 2191) were positive for HIV-1, 0.4% (n = 8) were positive for HIV-2 and 0.3% (n = 7) were dual infections (positive for both HIV-1 and HIV-2); 0.6% (n = 13) were indeterminate and 0.4% (n = 9) were negative. Further investigation of the 13 indeterminate results showed nine to be HIV-1 positive and four to be HIV-negative, for a total of 13 negative results. The positive predictive value of the HIV counselling and testing algorithm was 99.4%. Conclusion: Using the rapid testing algorithm alone, false positives were detected. Therefore, effective measures such as training and retraining of staff should be prioritised in order to minimise false-positive diagnoses and the associated potential for long-term psychological and financial impact on the patients.

Improving quality in national reference laboratories: the role of SLMTA and mentorship

Background: The Nigerian Institute of Medical Research houses two reference laboratories: the virology and tuberculosis laboratories. Both were enrolled in the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme. Objective: To describe the impact of SLMTA and discuss factors affecting the results; with an emphasis on mentorship Methods: The SLMTA programme was implemented from April 2010 through November 2012. Participants attended three workshops and executed quality improvement projects; laboratory auditors evaluated performance using a standard checklist. The virology laboratory did not receive mentorship; however; the tuberculosis laboratory had an international mentor who visited the laboratory four times during the programme; spending two to four weeks embedded within the laboratory during each visit. Results: There was an overall improvement in the performance of both laboratories; with the virology laboratory increasing 13% (from 80% at baseline to 93% at exit audit) and the tuberculosis laboratory increasing 29% (from 66% to 95%). These scores were maintained nine months later at the surveillance audit. Conclusion: The SLMTA programme resulted in improved and sustained quality management performance for both laboratories. Mentoring was a possible factor in the substantial improvement made by the tuberculosis laboratory and should be considered in order to augment the training received from the SLMTA workshops

Potential for false-positive HIV test results using rapid HIV testing algorithms

Background: In order to scale up access to HIV counselling and testing in Nigeria; an HIV diagnostic algorithm based on rapid testing was adopted. However; there was the need to further evaluate the testing strategy in order to better assess its performance; because of the potential for false positivity.Objectives: The objective of this study was to compare positive HIV test results obtained from the approved rapid testing algorithm with results from western blot tests performed on samples from the same patient.Methodology: A retrospective review was conducted of HIV screening and confirmatory results for patients seen between 2007 and 2008. Rapid test and western blot results were extracted and compared for concordance. Discordant results were further reviewed using a combination of HIV-1 RNA viral load and CD4+ cell count test results and clinical presentation from medical records. Results: Analysis of 2228 western blot results showed that 98.3% (n = 2191) were positive for HIV-1; 0.4% (n = 8) were positive for HIV-2 and 0.3% (n = 7) were dual infections (positive for both HIV-1 and HIV-2); 0.6% (n = 13) were indeterminate and 0.4% (n = 9) were negative. Further investigation of the 13 indeterminate results showed nine to be HIV-1 positive and four to be HIV-negative; for a total of 13 negative results. The positive predictive value of the HIV counselling and testing algorithm was 99.4%.Conclusion: Using the rapid testing algorithm alone; false positives were detected. Therefore; effective measures such as training and retraining of staff should be prioritised in order to minimise false-positive diagnoses and the associated potential for long-term psychological and financial impact on the patients

Proficiency testing for HIV, tuberculosis and malaria diagnosis in clinical laboratories in Nigeria.

BACKGROUND: Proficiency testing (PT) is a means of verifying the reliability of laboratory results, but such programmes are not readily available to laboratories in developing countries. This project provided PT to laboratories in Nigeria. OBJECTIVES: To assess the proficiency of laboratories in the diagnosis of HIV, tuberculosis and malaria. METHODS: This was a prospective study carried out between 2009 and 2011. A structured questionnaire was administered to 106 randomly-selected laboratories. Forty-four indicated their interest in participation and were enrolled. Four rounds of pre-characterised plasma panels for HIV, sputum films for tuberculosis and blood films for malaria were distributed quarterly by courier over the course of one year. The results were returned within two weeks and scores of ≥ 80% were reported as satisfactory. Mentoring was offered after the first and second PT rounds. RESULTS: Average HIV PT scores increased from 74% to 95% from the first round to the third round, but decreased in the fourth round. For diagnosis of tuberculosis, average scores increased from 42% in the first round to 78% in the second round; but a decrease to 34% was observed in the fourth round. Malaria PT performance was 2% at first, but average scores increased between the second and fourth rounds, culminating in a fourth-round score of 39%. Many participants requested training and mentoring. CONCLUSIONS: There were gross deficiencies in the quality of laboratory services rendered across Nigeria. In-country PT programmes, implemented in conjunction with mentoring, will improve coverage and diagnosis of HIV, tuberculosis and malaria.

Improving quality in national reference laboratories: The role of SLMTA and mentorship.

BACKGROUND: The Nigerian Institute of Medical Research houses two reference laboratories: the virology and tuberculosis laboratories. Both were enrolled in the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme. OBJECTIVE: To describe the impact of SLMTA and discuss factors affecting the results, with an emphasis on mentorship. METHODS: The SLMTA programme was implemented from April 2010 through November 2012. Participants attended three workshops and executed quality improvement projects; laboratory auditors evaluated performance using a standard checklist. The virology laboratory did not receive mentorship; however, the tuberculosis laboratory had an international mentor who visited the laboratory four times during the programme, spending two to four weeks embedded within the laboratory during each visit. RESULTS: There was an overall improvement in the performance of both laboratories, with the virology laboratory increasing 13% (from 80% at baseline to 93% at exit audit) and the tuberculosis laboratory increasing 29% (from 66% to 95%). These scores were maintained nine months later at the surveillance audit. CONCLUSION: The SLMTA programme resulted in improved and sustained quality management performance for both laboratories. Mentoring was a possible factor in the substantial improvement made by the tuberculosis laboratory and should be considered in order to augment the training received from the SLMTA workshops.

Genetic determinants of drug-resistant tuberculosis among HIV-infected patients in Nigeria.

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings. Adequate infrastructure for testing drug sensitivity and sufficient evidence of first-line resistance are currently unavailable in Nigeria. We collected sputum samples from HIV-infected patients enrolled in the Harvard PEPFAR/APIN Plus program over 12 months at two PEPFAR antiretroviral therapy (ART) clinics in the southwest and north central regions in Nigeria. Smear-positive sputum samples were submitted for GenoType MTBDRplus testing (n = 415); mutations were confirmed through sequencing. Our results show high rates of DR-TB in Nigerian HIV-infected individuals (7.0% for rifampin [RIF] and 9.3% for RIF or isoniazid [INH]). Total RIF resistance indicative of MDR-TB in treatment-naive patients was 5.52%, far exceeding the World Health Organization predictions (0 to 4.3%). RIF resistance was found in 6/213 (2.8%) cases, INH resistance was found in 3/215 (1.4%) cases, and MDR-TB was found in 8/223 (3.6%) cases. We found significantly different amounts of DR-TB by location (18.18% in the south of the country versus 3.91% in the north central region [P < 0.01]). Furthermore, RIF resistance was genetically distinct, suggesting possible location-specific strains are responsible for the transmission of drug resistance (P < 0.04). Finally, GenoType MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. We found that total DR-TB in HIV-infection is high and that transmission of drug-resistant TB in HIV-infected patients in Nigeria is higher than predicted.

Experience of quality management system in a clinical laboratory in Nigeria.

ISSUES: Quality-management systems (QMS) are uncommon in clinical laboratories in Nigeria, and until recently, none of the nation's 5 349 clinical laboratories have been able to attain the certifications necessary to begin the process of attaining international accreditation. Nigeria's Human Virology Laboratory (HVL), however, began implementation of a QMS in 2006, and in 2008 it was determined that the laboratory conformed to the requirements of ISO 9001:2000 (now 2008), making it the first diagnostic laboratory to be certified in Nigeria. The HVL has now applied for the World Health Organization (WHO) accreditation preparedness scheme. The experience of the QMS implementation process and the lessons learned therein are shared here. DESCRIPTION: In 2005, two personnel from the HVL spent time studying quality systems in a certified clinical laboratory in Dakar, Senegal. Following this peer-to-peer technical assistance, several training sessions were undertaken by HVL staff, a baseline assessment was conducted, and processes were established. The HVL has monitored its quality indicators and conducted internal and external audits; these analyses (from 2007 to 2009) are presented herein. LESSONS LEARNED: Although there was improvement in the pre-analytical and analytical indicators analysed and although data-entry errors decreased in the post-analytical process, the delay in returning laboratory test results increased significantly. There were several factors identified as causes for this delay and all of these have now been addressed except for an identified need for automation of some high-volume assays (currently being negotiated). Internal and external audits showed a trend of increasing non-conformities which could be the result of personnel simply becoming lax over time. Application for laboratory accreditation, however, could provide the renewed vigour needed to correct these non-conformities. RECOMMENDATION: This experience shows that sustainability of the QMS at present is a cause for concern. However, the tiered system of accreditation being developed by WHO-Afro may act as a driving force to preserve the spirit of continual improvement.

Experience of quality management system in a clinical laboratory in Nigeria

Issues: Quality-management systems (QMS) are uncommon in clinical laboratories in Nigeria; and until recently; none of the nation's 5 349 clinical laboratories have been able to attain the certifications necessary to begin the process of attaining international accreditation. Nigeria's Human Virology Laboratory (HVL); however; began implementation of a QMS in 2006; and in 2008 it was determined that the laboratory conformed to the requirements of ISO 9001:2000 (now 2008); making it the first diagnostic laboratory to be certified in Nigeria. The HVL has now applied for the World Health Organization (WHO) accreditation preparedness scheme. The experience of the QMS implementation process and the lessons learned there in are shared here. Description: In 2005; two personnel from the HVL spent time studying quality systems in a certified clinical laboratory in Dakar; Senegal. Following this peer-to-peer technical assistance; several training sessions were undertaken by HVL staff; a baseline assessment was conducted; and processes were established. The HVL has monitored its quality indicators and conducted internal and external audits; these analyses (from 2007 to 2009) are presented herein. Lessons learned: Although there was improvement in the pre-analytical and analytical indicators analysed and although data-entry errors decreased in the post-analytical process; the delay in returning laboratory test results increased significantly. There were several factors identified as causes for this delay and all of these have now been addressed except for an identified need for automation of some high-volume assays (currently being negotiated). Internal and external audits showed a trend of increasing non-conformities which could be the result of personnel simply becoming lax over time. Application for laboratory accreditation; however; could provide the renewed vigour needed to correct these non conformities. Recommendation: This experience shows that sustainability of the QMS at present is a cause for concern. However; the tiered system of accreditation being developed by WHO-Afro may act as a driving force to preserve the spirit of continual improvement

T-lymphocyte subsets in apparently healthy nigerian children.

Population studies showed that there are differences in T-lymphocytes subpopulation of normal children in different regions, and reference values in an area might be different from another. This study compared the values in our population with CDC and WHO reference values. Blood samples from 279 healthy, HIV-negative children <12 years of age were analysed for complete blood count, CD3+, CD4+, CD8+ counts and percentages. Except for CD8%, mean values for all parameters measured significantly decreased with age. CD4+ counts were higher in females than males, P < .05. Using the WHO criteria, 15.9% of subjects had low total lymphocyte count and 20.6% had low CD4 count. Children <3 years had median CD4% lower than WHO normal values. Our median CD4+ counts correlated with CDC values. Values used by WHO in infants are higher than ours. We suggest that our children be assessed using CDC reference values which correlate with ours.

Interplay of reverse transcriptase inhibitor therapy and gag p6 diversity in HIV type 1 subtype G and CRF02_AG.

Abstract The gag p6 region of HIV-1 has various nonsubstitutionary mutations, including insertions, duplications, deletions, and premature stop codons. Studies have linked gag p6 mutations to reduced susceptibility to antiretroviral therapy in HIV-1 subtype B. This study examined the relationship between antiretroviral therapy and gag p6 diversity in HIV-1 CRF02_AG and subtype G. p6 data were generated for secondary analyses following Viroseq genotyping of pol gene sequences in plasma samples from HIV-1-infected Nigerians on reverse transcriptase inhibitor therapy, with virologic failure (repeat VL > 2000 copies/ml). p6 sequence chromatograms were available for 40 CRF02_AG and 43 subtype G-infected individuals. Subjects who had not received their supply of antiretroviral drugs for at least 2 months prior to the plasma sampling were classified as nonadherent. p6 sequences from therapy-adherent individuals had more nonsubstitutionary mutations than sequences from drug-naive individuals (p = 0.0005). The P5L/T mutation was inversely correlated with the presence of K27Q/N in p6, with each mutation being more prominent in subtype G and CRF02_AG, respectively. The data also suggested that P5L/T may be a compensatory mutation for the loss of an essential phosphorylation site in p6. In addition, there was an inverse association between P5L/T mutations in p6 and thymidine analog mutations in reverse transcriptase (p = 0.0001), and drug nonadherence was associated with an 8-fold lower risk of having a nonsubstitutionary mutation in p6 (95% CI = 1.27-52.57). Our data suggest that antiretroviral therapy influences gag p6 diversity, but further studies are needed to clarify these observations.

Management of HIV-1 infection with a combination of nevirapine, stavudine, and lamivudine: a preliminary report on the Nigerian antiretroviral program.

OBJECTIVE: To evaluate treatment outcome in the first 12 months among HIV-positive patients managed with a combination of nevirapine + stavudine + lamivudine under the current national antiretroviral (ARV) program in Nigeria. DESIGN: This was a prospective observational, cohort study on 50 ARV-naive patients who met the inclusion criteria for the program and had given informed consent. All patients were in stage 2 or stage 3 periods of infection based on World Health Organization clinical classification. The patients were treated with the generic brands of ARVs and treatment consisted of oral nevirapine (Nevimal, Cipla, Mumbai, India), 200 mg daily, lamivudine (Lamivir, Cipla), 150 mg twice daily, and stavudine (Stavir, Cipla), 40 mg twice daily. Prior to initiation of treatment, the clinical history and baseline data for each patient were documented. The levels of plasma HIV-1 RNA, CD4 cell counts, frequency of opportunistic infections, and estimated body mass index were recorded at baseline and subsequently at intervals during treatment. Data obtained at the various sampling times for each parameter were compared against their baseline values. RESULTS: Data on the plasma HIV-1 RNA levels indicated that between baseline and week 24, the median viral load of the patients decreased by 1.79 log(10) copies/mL. Equally between baseline and week 48 the median CD4 cell counts increased by 186 x 10(6) cells/L, the frequency of opportunistic infections decreased by 82%, the median body mass index increased by 4.8 kg/m(2), and 36% experienced side effects, which were minor and transient. The most prevalent side effect recorded was skin rash associated with nevirapine. Good adherence to this triple regimen was recorded in >85% of the patients. CONCLUSIONS: The overall results within the 12-month treatment period indicated an effective suppression of viral replication, the reconstitution of the immune system, and improvement of the physical well-being of the study population. Though there may be differences in global distribution of the infecting HIV-1 subtypes, the clinical and biologic results of this study compared favorably to those documented in cohorts treated with branded and generic ARV drugs in some developed and developing countries. The cumulative data in this study further confirmed that the correct use of generic brands of ARVs is a feasible option in HIV care and support programs in resource-poor countries.