James Hakim

James Hakim
University of Zimbabwe | UZ · Department of Medicine

DSc (Medicine-HC)

About

242
Publications
32,101
Reads
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16,159
Citations
Citations since 2017
73 Research Items
7928 Citations
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201720182019202020212022202302004006008001,0001,200
201720182019202020212022202302004006008001,0001,200
Additional affiliations
January 2001 - present
University of Zimbabwe
Position
  • Professor
Description
  • HIV research-prevention and therapy HIV and comorbidities-TB
January 2001 - present
University of Zimbabwe
Position
  • Professor

Publications

Publications (242)
Article
Full-text available
Introduction Non-adherence to antiretroviral therapy (ART) is the main cause of viral non-suppression and its risk is increased by depression. In countries with high burden of HIV, there is a lack of trained professionals to deliver depression treatments. This paper describes the protocol for a 2-arm parallel group superiority 1:1 randomised contro...
Article
Background WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in...
Article
Background Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vi...
Article
Background: The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for...
Article
Background: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. Methods: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifap...
Article
Full-text available
Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested ph...
Article
Background: WHO treatment guidelines recommend tenofovir plus lamivudine or emtricitabine as the nucleoside reverse transcriptase inhibitor backbone in first-line regimens for HIV-infected adults. Lamivudine alone is not recommended, because of the risk of hepatitis B virus (HBV) resistance. We studied HBV responses in a large cohort of co-infecte...
Article
Objectives: To assess baseline prevalence of cryptococcal antigen (CrAg) positivity; and its contribution to reductions in all-cause mortality, deaths from cryptococcus and unknown causes, and new cryptococcal disease in the REALITY trial. Design: Retrospective CrAg testing of baseline and week-4 plasma samples in all 1805 African adults/childre...
Article
Background The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug–drug interactions with concomitantly used ART. Objectives To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. Methods Participant...
Article
Full-text available
Background Paediatric dolutegravir doses approved by stringent regulatory authorities (SRAs) for children weighing 20 kg to less than 40 kg until recently required 25 mg and 10 mg film-coated tablets. These tablets are not readily available in low-resource settings where the burden of HIV is highest. We did nested pharmacokinetic substudies in pati...
Article
Full-text available
Background: HIV affects the central nervous system resulting in HIV associated neurocognitive impairment (NCI) in approximately 50% of people living with HIV. It typically affects memory, learning, working memory, fine motor skills, speed of information processing, verbal fluency and executive functioning cognitive domains. NCI can affect adherenc...
Article
Full-text available
The trajectory, and impact of the SARS-CoV-2 pandemic in sub-Saharan Africa is unclear, but it is seemingly varied between different countries, with most reporting low numbers. We use the situation in Zimbabwe to build an argument that the epidemic is likely to be attenuated in some countries with similar socio-economic and cultural structures. How...
Article
Full-text available
Background Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vi...
Article
Background: Phylogenetic analysis can be used to assess HIV transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Methods: Complete next generation sequencing (NGS) data were obtained for 105 unique index-partner sampl...
Article
Full-text available
A retrospective analysis of the randomized controlled DART (Development of AntiRetroviral Therapy in Africa; ISRCTN13968779) trial in HIV-1-positive adults initiating antiretroviral therapy with co-formulated zidovudine/lamivudine plus either tenofovir, abacavir, or nevirapine was conducted to evaluate the safety of initiating standard lamivudine d...
Article
Background: Distal sensory peripheral neuropathy (DSPN) is a complication of human immunodeficiency virus (HIV). We estimate DSPN prevalence in 7 resource-limited settings (RLSs) for combination antiretroviral therapy (cART)-naive people living with HIV (PLWH) compared with matched participants not living with HIV and in PLWH virally suppressed on...
Article
Full-text available
Biobanks and human genomics applications are key for understanding health, disease and heredity in Africa and globally. Growing interest in these technologies calls for strengthening relevant legal, ethical and policy systems to address knowledge disparities and ensure protection of society, while supporting advancement of science. In Zimbabwe ther...
Article
Full-text available
BACKGROUND:Mapping of health-related quality-of-life measures to health utility values can facilitate cost-utility evaluation. Regression-based methods tend to lead to shrinkage of variance. This study aims to map the Medical Outcomes Study HIV Health Survey (MOS-HIV) to EuroQoL 5 Dimensions (EQ-5D-3 L) utility index, and to characterize the perfor...
Article
Objective: People living with HIV (PLWH) are at risk for HIV -Associated Neurocognitive Disorders (HAND)/Neurocognitive Impairment (NCI). HIV prevalence in Sub-Saharan Africa (SSA) is high, but neuropsychological screening and testing for NCI among HIV-infected individuals is not done frequently. This systematic review aims to establish how NCI amo...
Article
Full-text available
Background: Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates. Methods: We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-mont...
Article
Full-text available
Biobanks and human genomics applications are key for understanding health, disease and heredity in Africa and globally. Growing interest in these technologies calls for strengthening relevant legal, ethical and policy systems to address knowledge disparities and ensure protection of society, while supporting advancement of science. In Zimbabwe ther...
Article
Background: We evaluated use of phylogenetic methods to predict the direction of HIV transmission. Methods: For 33 index-partner pairs with genetically-linked infection, samples were collected from partners and indexes close to time of partners' seroconversion (SC); 31 indexes also had an earlier sample. Phylogenies were inferred using env next-...
Article
Full-text available
Background In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconsti- tution inflammatory syndrome (IRIS), a paradoxical response to succ...
Article
Full-text available
Background: In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to succe...
Article
BACKGROUND: In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have high mortality (10%) shortly after starting antiretroviral therapy (ART). This group also have the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integra...
Article
Background: Neurocognitive impairment remains a common complication of HIV despite effective antiretroviral therapy (ART). We previously reported improved neurocognitive functioning with ART initiation in seven resource limited settings (RLS) countries for HIV+ participants from AIDS Clinical Trials Group (ACTG) 5199 (International Neurological St...
Article
Background: AIDS Clinical Trial Group (ACTG) 5199 compared neurological and neuropsychological (NP) test performance of HIV-1+ participants in resource-limited settings (RLS) treated with three WHO recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes. Methods:...
Article
Full-text available
It has been postulated that the direction of HIV transmission between two individuals can be determined by phylogenetic analysis of HIV sequences. This approach may be problematic, since HIV sequences from newly infected individuals are often more similar to index sequences from samples collected years before transmission, compared to those from sa...
Article
Background: Limited viral load (VL) testing in HIV-infected individuals on treatment in low-income countries often results in late detection of treatment failure. The impact of remaining on failing second-line, protease inhibitor (PI) containing regimens is unclear. Methods: We retrospectively tested VL from 2,164 stored plasma samples from 386...
Article
Full-text available
Limited viral load (VL) testing in HIV-infected individuals on treatment in low-income countries often results in late detection of treatment failure. The impact of remaining on failing second-line, protease inhibitor (PI) containing regimens is unclear. We retrospectively tested VL from 2,164 stored plasma samples from 386 patients randomised to r...
Article
Full-text available
Background While barriers to uptake of antenatal care (ANC) among pregnant women have been explored, much less is known about how integrating prevention of mother-to-child transmission (PMTCT) programmes within ANC services affects uptake. We explored barriers to uptake of integrated ANC services in a poor Zimbabwean community. MethodsA cross-secti...
Article
Background & aims: Nutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART ini...
Article
Full-text available
Background: Major challenges are being experienced in medical education in sub-Saharan African Universities. These include emigration of faculty, infrequent curriculum review, inadequate training in medical education, poor investments in infrastructure and lack of faculty development programs. The USA government committed funding to improve the qu...
Article
Full-text available
An economic crisis in Zimbabwe from 1999–2009 resulted in a shortage of faculty at the University of Zimbabwe College of Health Sciences (UZCHS) and declining enrollment and graduation rates. To improve proficiency and retention of graduates, the college sought to develop a competency-based curriculum using evidence-based educational methodologies....
Article
Full-text available
Background: In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared wi...
Article
Full-text available
Background: Sub-Saharan Africa has an inadequate number of health professionals, leading to a reduced capacity to respond to health challenges, including HIV/AIDS. From 2010 to 2015, the Medical Education Partnership Initiative (MEPI)-sponsored by the U.S. Presidents Emergency Plan for AIDS Relief (PEPFAR) and the National Institutes of Health (NI...
Article
Background: In sub-Saharan Africa, 20%-25% of people starting antiretroviral therapy (ART) have severe immunosuppression; approximately 10% die within 3 months. In the Reduction of EArly mortaLITY (REALITY) randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced mortality vs cotrimoxazole. We investigate the contribution and t...
Article
Background. Severely immunocompromised human immunodefciency virus (HIV)-infected individuals have high mortality shortly afer starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods. Te Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children =5 years...
Article
Full-text available
Malawi, Uganda, and Zimbabwe have recently adopted a universal 'test-and-treat' approach to the prevention of mother-to-child transmission of HIV (Option B+). Amongst a largely asymptomatic population of women tested for HIV and immediately started on antiretroviral treatment (ART), a relatively high number are not retained in care; they are labell...
Article
Full-text available
Background: The Lablite project captured information on access to antiretroviral therapy (ART) at larger health facilities ('hubs') and lower-level health facilities ('spokes') in Phalombe district, Malawi and in Kalungu district, Uganda. Methods: We conducted a cross-sectional survey among patients who had transferred to a spoke after treatment...
Article
Introduction: We evaluated HIV drug resistance in adults who received early versus delayed antiretroviral therapy (ART) in a multi-national trial (HPTN 052, enrollment 2005-2010). In HPTN 052, 1,763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm3 (early ART arm) or <250 cells/mm3 (delayed ART arm). In May 2...
Article
Full-text available
BACKGROUND: Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standar...
Article
Full-text available
Background: Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standa...
Article
Full-text available
Background. The University of Zimbabwe College of Health Sciences (UZCHS), Harare, which has a long tradition of community-based education (CBE), has not been evaluated since 1991. An innovative approach was used to evaluate the programme during 2015. Objectives. To evaluate the CBE programme, using a peer-review model of evaluation and simultaneou...
Article
Full-text available
Background Epidemiological data on stroke in Zimbabwe are scarce and few clinical studies have been performed to date. Methods A retrospective review of the medical records of patients admitted for stroke during the year 2012 was performed at three tertiary hospitals. Sociodemographic data were recorded alongside with comorbidities and outcomes. S...
Article
Background In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. Methods In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi,...
Article
Background: Epidemiological data on stroke in Zimbabwe are scarce and few clinical studies have been performed to date. Methods: A retrospective review of the medical records of patients admitted for stroke during the year 2012 was performed at three tertiary hospitals. Sociodemographic data were recorded alongside with comorbidities and outcomes....
Article
Full-text available
To examine hepatitis B (HBV) serological markers and plasma DNA concentrations in a large group of untreated HBV/HIV-coinfected individuals in two sub-Saharan settings. Baseline analysis of a randomized controlled trial. DART was a large trial of treatment monitoring practices in HIV-infected adults with advanced disease starting antiretroviral the...
Article
Full-text available
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350–550 cells/mm³. A high resolution melting (HRM) assay was used to analyze baseline (pre-trea...
Data
Enrollment (baseline) characteristics of the study cohort (N = 95)*. (PDF)
Data
Distribution of baseline ENV2 HRM scores by geographical region. The box plot shows the distribution of ENV2 HRM scores by geographical region (South America [n = 17], Asia [n = 26], and Africa [n = 43]). Median (interquartile range [IQR]) ENV2 HRM scores were 5.4 (4.5, 6.0) for South America, 5.1 (4.4, 5.6) for Asia, and 4.4 (4.1, 5.4) for Africa....
Data
Kaplan-Meier plot showing the probability of ART failure as a function of time for participants with ENV1 HRM scores above vs. below the median. Kaplan-Meier plot showing the association of higher ENV1 HRM score (>median) with longer time to antiretroviral (ART) failure. The numbers below the graph indicate the number (N) of participants failing AR...
Data
High resolution melting (HRM) scores, geographical region, and HIV subtype of HIV-infected adults analyzed using the HRM diversity assay in HPTN 052. (PDF)
Data
Affiliated IRBs/ECs and regulatory bodies by site. (PDF)
Article
Full-text available
Background Cross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activ...
Article
Background: Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have been associated with body composition changes among HIV-infected persons with wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with ART initiation or differing ART therapies. Methods: The AIDS Clinical Trials Group Prospective Evaluat...
Article
Full-text available
Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. Objective: To evaluate factors associated with time to viral suppressi...
Article
Background: We conducted unlinked cross-sectional population-based surveys in Northern Uganda before and after antiretroviral therapy (ART) provision (including Option B+ [lifelong ART for pregnant/breast-feeding women]) at a local primary care facility (Lira Kato Health Centre [HC]). Prior to decentralisation, people travelled 56-76 km round-trip...
Article
Full-text available
Objectives: To examine hepatitis B serological markers and plasma DNA concentrations in a large group of untreated HIV-HBV co-infected individuals in two sub-Saharan settings. Design: Baseline analysis of a randomised controlled trial. Methods: DART was a large trial of treatment monitoring practices in HIV-infected adults with advanced diseas...
Article
Full-text available
Background Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively. MethodsDART compared clinically...
Article
Full-text available
Background: Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively. Methods: DART compared clinical...
Article
Objective: Tenofovir has in vitro activity against HSV-2 and reduced HSV-2 acquisition as pre-exposure prophylaxis. Whether tenofovir-containing antiretroviral therapy (ART) reduces HSV-2 acquisition is unknown. Design: Secondary analysis of ACTG A5175, a randomized, open-label study of three ART regimens among 1,571 participants. Methods: HSV...
Article
Full-text available
Cross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predic...