Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis.

BACKGROUND: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited. METHODS: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance. Deidentified demographic and clinical data were used to explore risk factors associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. RESULTS: Among the 1450 genotypes analyzed, 1048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1 or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI resistance was particularly high in children exposed to ARV drugs through PMTCT; adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only. CONCLUSIONS: Protease inhibitor-based regimens in children aged <3 years are currently recommended by WHO, but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.

HIV testing uptake and retention in care of HIV-infected pregnant and breastfeeding women initiated on 'Option B+' in rural Zimbabwe.

OBJECTIVES: Zimbabwe has started to scale up Option B+ for the prevention of mother-to-child transmission of HIV, but there is little published information about uptake or retention in care. This study determined the number and proportion of pregnant and lactating women in rural districts diagnosed with HIV infection and started on Option B+ along with six-month antiretroviral treatment (ART) outcomes. METHODS: This was a retrospective record review of women presenting to antenatal care or maternal and child health services at 34 health facilities in Chikomba and Gutu rural districts, Zimbabwe, between January and March 2014. RESULTS: A total of 2728 women presented to care of whom 2598 were eligible for HIV testing: 76% presented to antenatal care, 20% during labour and delivery and 4% while breastfeeding. Of 2097 (81%) HIV-tested women, 7% were HIV positive. Lower HIV testing uptake was found with increasing parity, late presentation to antenatal care, health centre attendance and in women tested during labour. Ninety-one per cent of the HIV-positive women were started on Option B+. Six-month ART retention in care, including transfers, was 83%. Loss to follow-up was the main cause of attrition. Increasing age and gravida status ≥2 were associated with higher six-month attrition. CONCLUSION: The uptake of HIV testing and Option B+ is high in women attending antenatal and post-natal clinics in rural Zimbabwe, suggesting that the strategy is feasible for national scale-up in the country.

Lower Levels of Antiretroviral Therapy Enrollment Among Men with HIV Compared with Women - 12 Countries, 2002-2013.

Equitable access to antiretroviral therapy (ART) for men and women with human immunodeficiency virus (HIV) infection is a principle endorsed by most countries and funding bodies, including the U.S. President's Emergency Plan for AIDS (acquired immunodeficiency syndrome) Relief (PEPFAR) (1). To evaluate gender equity in ART access among adults (defined for this report as persons aged ≥15 years), 765,087 adult ART patient medical records from 12 countries in five geographic regions* were analyzed to estimate the ratio of women to men among new ART enrollees for each calendar year during 2002-2013. This annual ratio was compared with estimates from the Joint United Nations Programme on HIV/AIDS (UNAIDS)(†) of the ratio of HIV-infected adult women to men in the general population. In all 10 African countries and Haiti, the most recent estimates of the ratio of adult women to men among new ART enrollees significantly exceeded the UNAIDS estimates for the female-to-male ratio among HIV-infected adults by 23%-83%. In six African countries and Haiti, the ratio of women to men among new adult ART enrollees increased more sharply over time than the estimated UNAIDS female-to-male ratio among adults with HIV in the general population. Increased ART coverage among men is needed to decrease their morbidity and mortality and to reduce HIV incidence among their sexual partners. Reaching more men with HIV testing and linkage-to-care services and adoption of test-and-treat ART eligibility guidelines (i.e., regular testing of adults, and offering treatment to all infected persons with ART, regardless of CD4 cell test results) could reduce gender inequity in ART coverage.

Long Turnaround Times in Viral Load Monitoring of People Living with HIV in Resource-Limited Settings.

INTRODUCTION: Routine viral load (VL) testing is fraught with challenges in resource-limited settings which lead to longer turnaround times for the return of VL results. We assessed the turnaround times for VL testing and factors associated with long turnaround (>30 days) in Marondera, Zimbabwe, between January and September 2018. METHODS: This was an analytical study of routine program data. Data were extracted from electronic records and paper-based reports at two laboratories and at antiretroviral therapy (ART) facilities. The unit of analysis was the VL sample. Duration (in days) between sample collection and sample testing (pre-test turnaround time), duration between sample testing and receipt of VL result at ART the site (post-test turnaround time), and duration between sample collection and receipt of result at the ART site (overall turnaround time) were calculated. Days on which the VL testing machine was not functional, and workload (number of tests done per month) were used to assess associations. We used binomial log models to assess the factors associated with longer turnaround time. RESULTS: A total of 3348 samples were received at the two VL testing laboratories, and 3313 were tested, of these, 1111 were analyzed for overall turnaround time. Pre-test, post-test, and overall turnaround times were 22 days (interquartile range (IQR): 11-41), 51 days (IQR: 30-89), and 67 days (IQR: 46-100), respectively. Laboratory workload (relative risk [RR]: 1.12, 95% confidence interval [CI]: 1.10-1.14) and machine break down (RR: 1.15, 95% CI: 1.14-1.17) were associated with long turnaround time. CONCLUSIONS: Routine VL turnaround time was long. Decentralizing VL testing and enhancing laboratory capacity may help shorten the turnaround time.

Comprehensive investigation of sources of misclassification errors in routine HIV testing in Zimbabwe.

INTRODUCTION: Misclassification errors have been reported in rapid diagnostic HIV tests (RDTs) in sub-Saharan African countries. These errors can lead to missed opportunities for prevention-of-mother-to-child-transmission (PMTCT), early infant diagnosis and adult HIV-prevention, unnecessary lifelong antiretroviral treatment (ART) and wasted resources. Few national estimates or systematic quantifications of sources of errors have been produced. We conducted a comprehensive assessment of possible sources of misclassification errors in routine HIV testing in Zimbabwe. METHODS: RDT-based HIV test results were extracted from routine PMTCT programme records at 62 sites during national antenatal HIV surveillance in 2017. Positive- (PPA) and negative-percent agreement (NPA) for HIV RDT results and the false-HIV-positivity rate for people with previous HIV-positive results ("known-positives") were calculated using results from external quality assurance testing done for HIV surveillance purposes. Data on indicators of quality management systems, RDT kit performance under local climatic conditions and user/clerical errors were collected using HIV surveillance forms, data-loggers and a Smartphone camera application (7 sites). Proportions of cases with errors were compared for tests done in the presence/absence of potential sources of errors. RESULTS: NPA was 99.9% for both pregnant women (N = 17224) and male partners (N = 2173). PPA was 90.0% (N = 1187) and 93.4% (N = 136) for women and men respectively. 3.5% (N = 1921) of known-positive individuals on ART were HIV negative. Humidity and temperature exceeding manufacturers' recommendations, particularly in storerooms (88.6% and 97.3% respectively), and premature readings of RDT output (56.0%) were common. False-HIV-negative cases, including interpretation errors, occurred despite staff training and good algorithm compliance, and were not reduced by existing external or internal quality assurance procedures. PPA was lower when testing room humidity exceeded 60% (88.0% vs. 93.3%; p = 0.007). CONCLUSIONS: False-HIV-negative results were still common in Zimbabwe in 2017 and could be reduced with HIV testing algorithms that use RDTs with higher sensitivity under real-world conditions and greater practicality under busy clinic conditions, and by strengthening proficiency testing procedures in external quality assurance systems. New false-HIV-positive RDT results were infrequent but earlier errors in testing may have resulted in large numbers of uninfected individuals being on ART.

Anti-retroviral therapy after "Treat All" in Harare, Zimbabwe: What are the changes in uptake, time to initiation and retention?

Background: In Zimbabwe, Harare was the first province to implement "Treat All" for people living with human immunodeficiency virus (PLHIV). Since its roll out in July 2016, no study has been conducted to assess the changes in key programme indicators. We compared antiretroviral therapy (ART) uptake, time to ART initiation from diagnosis, and retention before and during "Treat All". Methods: We conducted an ecological study to assess ART uptake among all PLHIV newly diagnosed before and during "Treat All". We conducted a cohort study to assess time to ART initiation and retention in care among all PLHIV newly initiated on ART from all electronic patient management system-supported sites (n=50) before and during "Treat All". Results: ART uptake increased from 65% (n=4619) by the end of quarter one, 2014 to 85% (n=5152) by the end of quarter four, 2018.  A cohort of 2289 PLHIV were newly initiated on ART before (April-June 2015) and 1682 during "Treat all" (April-June 2017). Their age and gender distribution was similar. The proportion of PLHIV in early stages of disease was significantly higher during "Treat all" (73.2% vs. 55.6%, p<0.001). The median time to ART initiation was significantly lower during "Treat All" (31 vs. 88 days, p<0.001). Cummulative retention at three, six and 12 months was consistently lower during "Treat all" and was significant at six months (74.9% vs.78.1% p=0.022). Conclusion: Although there were benefits of early ART initiation during "Treat All", the programme should consider strategies to improve retention.

Children and adolescents on anti-retroviral therapy in Bulawayo, Zimbabwe: How many are virally suppressed by month six?

Background: Zimbabwe is one of the countries in sub-Saharan Africa disproportionately affected by human immunodeficiency virus. In the "treat all" era, we assessed the gaps in routine viral load (VL) monitoring at six months for children (0-9 years) and adolescents (10-19 years) newly initiated on anti-retroviral therapy (ART) from January 2017 to September 2018 at a large tertiary hospital in Bulawayo. Methods: In this cohort study using secondary data, we considered first VL done within six to nine months of starting therapy as 'undergoing VL test at six months'. We classified repeat VL≥1000 copies/ml despite enhanced adherence counselling as virally unsuppressed. Results: Of 295 patients initiated on ART, 196 (66%) were children and 99 (34%) adolescents. A total 244 (83%) underwent VL test at six months, with 161 (54%) virally suppressed, 52 (18%) unsuppressed and 82 (28%) with unknown status (due to losses in the cascade). Switch to second line was seen in 35% (18/52). When compared to children, adolescents were less likely to undergo a VL test at six months (73% versus 88%, p=0.002) and more likely to have an unknown VL status (40% versus 22%, p=0.001). Conclusion: At six months of ART, viral suppression was low and losses in the cascade high.

Retention and predictors of attrition among patients who started antiretroviral therapy in Zimbabwe's national antiretroviral therapy programme between 2012 and 2015.

BACKGROUND: The last evaluation to assess outcomes for patients receiving antiretroviral therapy (ART) through the Zimbabwe public sector was conducted in 2011, covering the 2007-2010 cohorts. The reported retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. We report findings of a follow-up evaluation for the 2012-2015 cohorts to assess the implementation and impact of recommendations from this prior evaluation. METHODS: A nationwide retrospective study was conducted in 2016. Multi-stage proportional sampling was used to select health facilities and study participants records. The data extracted from patient manual records included demographic, baseline clinical characteristics and patient outcomes (active on treatment, died, transferred out, stopped ART and lost to follow-up (LTFU)) at 6, 12, 24 and 36 months. The data were analysed using Stata/IC 14.2. Retention was estimated using survival analysis. The predictors associated with attrition were determined using a multivariate Cox regression model. RESULTS: A total of 3,810 participants were recruited in the study. The median age in years was 35 (IQR: 28-42). Overall, retention increased to 92.4% (p-value = 0.060), 86.5% (p-value<0.001), 79.2% (p-value<0.001) and 74.4% (p-value<0.001) at 6, 12, 24 and 36 months respectively. LTFU accounted for 98% of attrition. Being an adolescent or a young adult (15-24 years) (vs adult;1.41; 95% CI:1.14-1.74), children (<15years) (vs adults; aHR 0.64; 95% CI:0.46-0.91), receiving care at primary health care facility (vs central and provincial facility; aHR 1.23; 95% CI:1.01-1.49), having initiated ART between 2014-2015 (vs 2012-2013; aHR1.45; 95%CI:1.24-1.69), having WHO Stage IV (vs Stage I-III; aHR2.06; 95%CI:1.51-2.81) and impaired functional status (vs normal status; aHR1.25; 95%CI:1.04-1.49) predicted attrition. CONCLUSION: The overall retention was higher in comparison to the previous 2007-2010 evaluation. Further studies to understand why attrition was found to be higher at primary health care facilities are warranted. Implementation of strategies for managing patients with advanced HIV disease, differentiated care for adolescents and young adults and tracking of LTFU clients should be prioritised to further improve retention.

Prevalence, risk factors and treatment outcomes of isoniazid resistant TB in Bulawayo city, Zimbabwe: A cohort study.

INTRODUCTION: The isoniazid-resistant TB poses a threat to TB control efforts. Zimbabwe, one of the high TB burden countries, has not explored the burden of isoniazid resistant TB. Hence among all bacteriologically-confirmed TB patients diagnosed in Bulawayo City during March 2017 and December 2018, we aimed to assess the proportion with isoniazid resistant TB and associated factors. Also, we aimed to describe the TB treatment outcomes. METHODOLOGY: A cohort study involving routinely collected data by the National TB Reference Laboratory (NTBRL) in Bulawayo City and National TB programme of Zimbabwe. The percentage with 95% confidence interval (CI) was used to express the proportion with isoniazid-resistant TB. The modified Poisson regression was used to assess the association of demographic and clinical characteristics with isoniazid mono-resistant TB. RESULTS: Of 2160 bacteriologically-confirmed TB patients, 1612 (74.6%) had their sputum received at the NTBRL and 743 (46.1%) had culture growth. Among those with culture growth, 34 (4.6%, 95% CI: 3.5-6.7) had isoniazid mono-resistant TB, 25 (3.3%, 95% CI: 2.2-4.9) had MDR-TB. Thus, 59 (7.9%, 95% CI: 6.1-10.1) had isoniazid-resistant TB. Children < 15 years had a higher prevalence of isoniazid mono-resistant TB (aPR= 3.93; 95% CI: 1.24-12.45). Among those with rifampicin sensitive TB, patients with isoniazid-sensitive TB had higher favourable treatment outcomes compared to those with isoniazid-resistant TB (86.3% versus 75.5%, p = 0.039). CONCLUSIONS: The prevalence of isoniazid-resistant TB was low compared to neighbouring countries with high burden of TB-HIV. However, Zimbabwe should consider reviewing treatment guidelines for isoniazid mono-resistant TB due to the observed poor treatment outcomes.

High levels of resistance to nucleoside/nucleotide reverse transcriptase inhibitors in newly diagnosed antiretroviral treatment-naive children in sub-Saharan Africa.

: Exposure of infants to antiretroviral drugs for prevention of mother-to-child transmission can induce resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). Data from nine national surveys of pretreatment drug resistance in children newly diagnosed with HIV show high levels of resistance to NRTIs included in first-line antiretroviral treatment (ART) regimens (dual abacavir-lamivudine/emtricitabine resistance). Additional research is needed to determine the impact of NRTI resistance on treatment response and optimize infant ART.

Retesting for verification of HIV diagnosis before antiretroviral therapy initiation in Harare, Zimbabwe: Is there a gap between policy and practice?

BACKGROUND: WHO recommends retesting of HIV-positive patients before starting antiretroviral therapy (ART). There is no evidence on implementation of retesting guidelines from programmatic settings. We aimed to assess implementation of HIV retesting among clients diagnosed HIV-positive in the public health facilities of Harare, Zimbabwe, in June 2017. METHODS: This cohort study involved analysis of secondary data collected routinely by the programme. RESULTS: Of 1729 study participants, 639 (37%) were retested. Misdiagnosis of HIV was found in six (1%) of the patients retested-all were infants retested with DNA-PCR. There was no HIV misdiagnosis among adults. Among those retested, 95% were retested on the same day and two-thirds were tested by a different provider as per national guidelines. Among those retested and found positive, 95% were started on ART, while none of those with negative retest results were started on ART. Of those not retested, about half (51%) were started on ART. The median (IQR) time to ART initiation from diagnosis was 0 (0-1) d. CONCLUSION: The implementation of HIV-retesting policy in Harare was poor. While most HIV retest positives were started on ART, only half non-retested received ART. Future research is needed to understand the reasons for non-retesting and non-initiation of ART among those not retested.

Increasing levels of pretreatment HIV drug resistance and safety concerns for dolutegravir use in women of reproductive age.

: Use of dolutegravir-based first-line antiretroviral therapy (ART) in response to rising levels of pretreatment HIV drug resistance (PDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) may be limited, given safety concerns for birth defects in women of child-bearing potential. Pooled data from 11 nationally representative surveys show that NNRTI PDR in women is nearly twice that in men, exceeding 10% in 8 of 11 countries monitored, suggesting the urgent need for a non-NNRTI-based ART regimen in this population.

HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis.

BACKGROUND: Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs. METHODS: This study was a systematic review and meta-regression analysis. We assessed regional prevalence of pretreatment drug resistance and risk of pretreatment drug resistance in people initiating ART who reported previous ART exposure. We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs. We searched for studies in PubMed and Embase and conference abstracts and presentations from the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society Conference, and the International Drug Resistance Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of drug resistance within a specified region at any specific timepoint, we extracted study level data and pooled prevalence estimates within the region using an empty logistic regression model with a random effect at the study level. We used random effects meta-regression to relate sampling year to prevalence of pretreatment drug resistance within geographical regions. FINDINGS: We identified 358 datasets that contributed data to our analyses, representing 56 044 adults in 63 countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11·0% (7·5-15·9) in southern Africa, 10·1% (5·1-19·4) in eastern Africa, 7·2% (2·9-16·5) in western and central Africa, and 9·4% (6·6-13·2) in Latin America and the Caribbean. There were substantial increases in pretreatment NNRTI resistance per year in all regions. The yearly increases in the odds of pretreatment drug resistance were 23% (95% CI 16-29) in southern Africa, 17% (5-30) in eastern Africa, 17% (6-29) in western and central Africa, 11% (5-18) in Latin America and the Caribbean, and 11% (2-20) in Asia. Estimated increases in the absolute prevalence of pretreatment drug resistance between 2015 and 2016 ranged from 0·3% in Asia to 1·8% in southern Africa. INTERPRETATION: Pretreatment drug resistance is increasing at substantial rate in LMICs, especially in sub-Saharan Africa. In 2016, the prevalence of pretreatment NNRTI resistance was near WHO's 10% threshold for changing first-line ART in southern and eastern Africa and Latin America, underscoring the need for routine national HIV drug-resistance surveillance and review of national policies for first-line ART regimen composition. FUNDING: Bill & Melinda Gates Foundation and World Health Organization.

Does nonlocal women's attendance at antenatal clinics distort HIV prevalence surveillance estimates in pregnant women in Zimbabwe?

OBJECTIVE: The objective was to assess whether HIV prevalence measured among women attending antenatal clinics (ANCs) are representative of prevalence in the local area, or whether estimates may be biased by some women's choice to attend ANCs away from their residential location. We tested the hypothesis that HIV prevalence in towns and periurban areas is underestimated in ANC sentinel surveillance data in Zimbabwe. METHODS: National unlinked anonymous HIV surveillance was conducted at 19 ANCs in Zimbabwe in 2000, 2001, 2002, 2004, 2006, 2009, and 2012. This data was used to compare HIV prevalence and nonlocal attendance levels at ANCs at city, town, periurban, and rural clinics in aggregate and also for individual ANCs. RESULTS: In 2000, HIV prevalence at town ANCs (36.6%, 95% CI 34.4-38.9%) slightly underestimated prevalence among urban women attending these clinics (40.7%, 95% CI 37.6-43.9%). However, there was no distortion in HIV prevalence at either the aggregate clinic location or at individual clinics in more recent surveillance rounds. HIV prevalence was consistently higher in towns and periurban areas than in rural areas. Nonlocal attendance was high at town (26-39%) and periurban (53-95%) ANCs but low at city clinics (<10%). However, rural women attending ANCs in towns and periurban areas had higher HIV prevalence than rural women attending rural clinics, and were younger, more likely to be single, and less likely to be housewives. CONCLUSIONS: In Zimbabwe, HIV prevalence among ANC attendees provides reliable estimates of HIV prevalence in pregnant women in the local area.

Empirical validation of the UNAIDS Spectrum model for subnational HIV estimates: case-study of children and adults in Manicaland, Zimbabwe.

BACKGROUND: More cost-effective HIV control may be achieved by targeting geographical areas with high infection rates. The AIDS Impact model of Spectrum - used routinely to produce national HIV estimates - could provide the required subnational estimates but is rarely validated with empirical data, even at a national level. DESIGN: The validity of the Spectrum model estimates were compared with empirical estimates. METHODS: Antenatal surveillance and population survey data from a population HIV cohort study in Manicaland, East Zimbabwe, were input into Spectrum 5.441 to create a simulation representative of the cohort population. Model and empirical estimates were compared for key demographic and epidemiological outcomes. Alternative scenarios for data availability were examined and sensitivity analyses were conducted for model assumptions considered important for subnational estimates. RESULTS: Spectrum estimates generally agreed with observed data but HIV incidence estimates were higher than empirical estimates, whereas estimates of early age all-cause adult mortality were lower. Child HIV prevalence estimates matched well with the survey prevalence among children. Estimated paternal orphanhood was lower than empirical estimates. Including observations from earlier in the epidemic did not improve the HIV incidence model fit. Migration had little effect on observed discrepancies - possibly because the model ignores differences in HIV prevalence between migrants and residents. CONCLUSION: The Spectrum model, using subnational surveillance and population data, provided reasonable subnational estimates although some discrepancies were noted. Differences in HIV prevalence between migrants and residents may need to be captured in the model if applied to subnational epidemics.

Results from implementing updated 2012 World Health Organization Guidance on early-warning indicators of HIV drug resistance in Zimbabwe.

OBJECTIVE: This study evaluated the performance of sentinel sites in preventing the emergence of HIVDR using Early Warning Indicators (HIVDR EWI) survey. METHODS: Adult and paediatric patient data on: On time pill pick up, Retention in care, Pharmacy stock-outs, and Dispensing practices was collected. Information from pharmacy registers was verified using facility-held cards. This was a cross-sectional analysis of retrospectively collected data from 72 sites providing both adult and paediatric ART as well as two providing adult ART only. All data were entered into and analysed using a WHO EWI data abstraction electronic tool. RESULTS: Twenty-one percent of sites providing adult and 4.2% of sites providing paediatric ART managed to meet the target for on time pill pick up. Retention in care indicator was met by 48.7% (95% CI: 36.9-60.6) of sites. ARV stock-outs occurred in 81.1% (95% CI: 70-89.3) adult sites and 63.9% (95% CI: 50-78.6) paediatric sites. ARVs were appropriately dispensed by 86.5% (95% CI: 75.6-93.3) of adult sites and 84.7% (95% CI: 74.3-92.1) of paediatric sites. CONCLUSIONS: Most sites had low performance in many indicators in this survey and failed to meet the recommended targets. Some policies such as the current buffer stock and storage outside Harare should be revised in order to improve site access to ARVs. The country should prioritize the provision of viral load testing services in all provinces. The electronic patient management system should be rolled out to all ART sites to improve patient tracking and monitoring by sites.

Pre-treatment drug resistance among patients initiating antiretroviral therapy (ART) in Zimbabwe: 2008-2010.

BACKGROUND: Zimbabwe set up 12 sentinel sites to monitor HIV drug resistance (HIVDR) following the international standards for prevention of HIVDR from 2008 to 2010. METHODS: Participants were consecutively enrolled. Blood was collected and used for CD4 count, viral load (VL) and pre-treatment DR (PDR) tests besides routine baseline tests. We analyzed the characteristics of participants enrolled into the survey and estimated the point prevalence of PDR and its associated factors among ART initiators in a cross-sectional analysis using the baseline data collected from a prospective cohort in 12 purposefully selected sentinel sites. RESULTS: A total of 1728 participants (96 % response rate) were enrolled and 1610 had complete data. Of the 1610 there were more females (68.7 %) than males (31.3 %). The median CD4 count was 168 cells/mm(3) with males having lower values (P = 0.003). Ninety-six percent of participants had a VL ≥ 1000 copies/ml and the median VL was 128,000. Previous exposure to antiretroviral drugs (ARVs) was mainly through PMTCT (5 % of the participants). Overall, PDR mutations were detected in 6.3 % (95 % CI 5.2-7.7) of the 1480 successfully genotyped participants. However, the prevalence of PDR mutations was double for those with previous exposure (12.1 %) to ARVs compared with those without previous exposure (5.7 %, P = 0.002). CONCLUSIONS: The results show a moderate level of PDR prevalence among ART initiators. To maintain the efficacy of the current first-line regimens, there is need to strengthen all HIVDR prevention efforts and to conduct further studies to investigate optimal strategies that can prolong the efficacy of first-line ARV regimens in the country.

Within-Gender Changes in HIV Prevalence among Adults between 2005/6 and 2010/11 in Zimbabwe.

INTRODUCTION: Zimbabwe has reported significant declines in HIV prevalence between 2005/06 and 2010/11 Demography and Health Surveys; a within-gender analysis to identify the magnitude and factors associated with this change, which can be masked, is critical for targeting interventions. METHODS: We analyzed change in HIV prevalence for 6,947 women and 5,848 men in the 2005/06 survey and 7,313 women and 6,250 men in 2010/11 surveys using 2005/06 as referent. The data was analyzed taking into consideration the survey design and therefore the svy, mean command in Stata was used in both linear and logistic regression. RESULTS: There were similar proportional declines in prevalence at national level for males (15% p=0.011) and females (16%,p=0.008). However, there were variations in decline by provincial setting, demographic variables of age, educational level and some sexual risk behaviours. In logistic regression analysis, statistically significant declines were observed among men in Manicaland, Mashonaland East and Harare (p<0.01) and for women in Manicaland, Mashonaland Central and Harare (p<0.01). Although not statistically significant, numerical increases were observed among men in Matebeleland North, Matebeleland South, Midlands and for both men and women in Bulawayo. Young women in the age range 15-34 experienced a decline in prevalence (p<0.01) while older men 30-44 had a statistically significant decline (p<0.01). Having a secondary and above education, regardless of employment status for both men and women recorded a significant decline. For sexual risk behaviours, currently in union for men and women and not in union for women there was a significant decline in prevalence. CONCLUSION: Zimbabwe has reported a significant decline among both men and women but there are important differentials across provinces, demographic characteristics and sexual risk behaviours that suggest that the epidemic in Zimbabwe is heterogeneous and therefore interventions must be targeted in order to achieve epidemic control.

Patient retention, clinical outcomes and attrition-associated factors of HIV-infected patients enrolled in Zimbabwe's National Antiretroviral Therapy Programme, 2007-2010.

BACKGROUND: Since establishment of Zimbabwe's National Antiretroviral Therapy (ART) Programme in 2004, ART provision has expanded from <5,000 to 369,431 adults by 2011. However, patient outcomes are unexplored. OBJECTIVE: To determine improvement in health status, retention and factors associated with attrition among HIV-infected patients on ART. METHODS: A retrospective review of abstracted patient records of adults ≥ 15 years who initiated ART from 2007 to 2009 was done. Frequencies and medians were calculated for rates of retention in care and changes in key health status outcomes at 6, 12, 24 and 36 months respectively. Cox proportional hazards models were used to determine factors associated with attrition. RESULTS: Of the 3,919 patients, 64% were female, 86% were either WHO clinical stage III or IV. Rates of patient retention at 6, 12, 24 and 36 months were 90.7%, 78.1%, 68.8% and 64.4%, respectively. After ART initiation, median weight gains at 6, 12, and 24 months were 3, 4.5, and 5.0 kgs whilst median CD4+ cell count gains at 6, 12 and 24 months were 122, 157 and 279 cells/µL respectively. Factors associated with an increased risk of attrition included male gender (AHR 1.2; 95% CI, 1.1-1.4), baseline WHO stage IV (AHR 1.7; 95% CI, 1.1-2.6), lower baseline body weight (AHR 2.0; 95% CI, 1.4-2. 8) and accessing care from higher level healthcare facilities (AHR 3.5; 95% 1.1-11.2). CONCLUSIONS: Our findings with regard to retention as well as clinical and immunological improvements following uptake of ART, are similar to what has been found in other settings. Factors influencing attrition also mirror those found in other parts of sub-Saharan Africa. These findings suggest the need to strengthen earlier diagnosis and treatment to further improve treatment outcomes. Whilst decentralisation improves ART coverage it should be coupled with strategies aimed at improving patient retention.

Acute oral toxicity and neurobehavioural toxicological effects of hydroethanolic extract of Boophone disticha in rats.

Boophone disticha (B. disticha) has been used systemically in traditional medical practice in Zimbabwe and neighbouring countries for the management of various central nervous system conditions including hysteria. Abuse of the plant by teenagers in Zimbabwe for its claimed hallucinogenic effects has also been reported, with the advent of serious toxicity in some cases. In the present work, we describe the acute toxicity and neurotoxicological effects of a freeze dried hydro-ethanolic plant extract of the bulb of B. disticha. Thirty-three adult (6-12 weeks old), non-pregnant female Sprague Dawley rats were used for the oral LD(50) estimation. Animals were given doses of 50, 120, 240, 360, 500 and 700 mg/kg and were observed using a modified Functional Observation Battery (FOB) for behavioural toxicity. The estimated oral LD(50) of the plant extract was between 120 and 240 mg/kg. For doses of 240 mg/kg and less, signs of toxicity began approximately 10 minutes after gavage, and the most prominent initial signs were head tremors (at 50 mg/kg) and body tremors, severe body tremors(>360 mg/kg) followed by convulsions. Generally, symptoms of toxicity lasted approximately 2 hours for doses of 240 mg/kg and less; and 3 hours for doses over 240 mg/kg for animals that survived. These results point to a rapid gastrointestinal absorption of the active principles in the plant extract. The most prominent neurotoxicological effects were increased flaccid limb paralysis and spastic hind-limb paralysis. Tachypnoea was noted at low doses and higher doses produced laboured breathing. The retropulsion observed with higher doses could indicate the reported hallucinogenic effects of the plant extract.