National prevalence and trends of HIV transmitted drug resistance in Mexico

Background

Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access.

Methodology/Principal Findings

We designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naïve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2∶8.8) and 6.8% (95% CI, 5.7∶8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (p = 0.0456) and PI (p = 0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects.

Conclusions

TDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed.     

Antiretroviral treatment for HIV in rural Uganda: two-year treatment outcomes of a prospective health centre/community-based and hospital-based cohort

Background

In sub-Saharan Africa, a shortage of trained health professionals and limited geographical access to health facilities present major barriers to the expansion of antiretroviral therapy (ART). We tested the utility of a health centre (HC)/community-based approach in the provision of ART to persons living with HIV in a rural area in western Uganda.

Methods

The HIV treatment outcomes of the HC/community-based ART program were evaluated and compared with those of an ART program at a best-practice regional hospital. The HC/community-based cohort comprised 185 treatment-naïve patients enrolled in 2006. The hospital cohort comprised of 200 patients enrolled in the same time period. The HC/community-based program involved weekly home visits to patients by community volunteers who were trained to deliver antiretroviral drugs to monitor and support adherence to treatment, and to identify and report adverse reactions and other clinical symptoms. Treatment supporters in the homes also had the responsibility to remind patients to take their drugs regularly. ART treatment outcomes were measured by HIV-1 RNA viral load (VL) after two years of treatment. Adherence was determined through weekly pill counts.

Results

Successful ART treatment outcomes in the HC/community-based cohort were equivalent to those in the hospital-based cohort after two years of treatment in on-treatment analysis (VL≤400 copies/mL, 93.0% vs. 87.3%, p = 0.12), and in intention-to-treat analysis (VL≤400 copies/mL, 64.9% and 62.0%, p = 0.560). In multivariate analysis patients in the HC/community-based cohort were more likely to have virologic suppression compared to hospital-based patients (adjusted OR = 2.47, 95% CI 1.01–6.04).

Conclusion

Acceptable rates of virologic suppression were achieved using existing rural clinic and community resources in a HC/community-based ART program run by clinical officers and supported by lay volunteers and treatment supporters. The results were equivalent to those of a hospital-based ART program run primarily by doctors.     

Low-Abundance HIV Drug-Resistant Viral Variants in Treatment-Experienced Persons Correlate with Historical Antiretroviral Use

Background

It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown.

Methodology/Principal Findings

Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004–2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85–5.53). The additional low-abundance drug-resistant mutations increased a subject''s genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects'' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5–74.3, p = 0.0016).

Conclusions/Significance

Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject''s overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with historical antiretroviral use. Ultra-deep sequencing can provide important historical resistance information for clinicians when planning subsequent antiretroviral regimens for highly treatment-experienced patients, particularly when their prior treatment histories and longitudinal genotypes are not available.     

Antiretroviral therapy outcomes in HIV-infected children after adjusting protease inhibitor dosing during tuberculosis treatment

Background

Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.

Methods and Findings

A medical record review was conducted at two clinical sites in Johannesburg, South Africa. The records of children 6–24 months of age initiating LPV/r-based therapy were reviewed. Children co-treated for TB were categorized based on the modifications made to their ART regimen and were compared to children of the same age at each site not treated for TB.Included are 526 children, 294 (56%) co-treated for TB. All co-treated children had more severe HIV disease, including lower CD4 percents and worse growth indicators, than comparisons.Children in the super-boosted group (n = 156) were as likely to be virally suppressed (<400 copies/ml) at 6 months as comparisons (69.2% vs. 74.8%, p = 0.36). Children in the double-dose (n = 47) and ritonavir groups (n = 91) were significantly less likely to be virally suppressed at 6 months (53.1% and 49.3%) than comparisons (74.8% and 82.1%; p = 0.02 and p<0.0001, respectively). At 12 months only children in the ritonavir group still had lower rates of virological suppression relative to comparisons (63.9% vs 83.3% p<0.05). Grade 1 or greater ALT elevations were more common in the super-boosted (75%) than double-dose (54.6%) or ritonavir (33.9%) groups (p = 0.09 and p<0.0001) but grade 3/4 elevations were observed in 3 (13.6%) of the super-boosted, 7 (15.9%) of the double-dose and 5 (8.9%) of the ritonavir group (p = 0.81 and p = 0.29).

Conclusion

Good short-term virologic outcomes were achieved in children co-treated for TB and HIV who received super-boosted LPV/r. Treatment limiting toxicity was rare. Strategies for increased dosing of LPV/r with TB treatment warrant further investigation.     

Transmitted antiretroviral drug resistance in new york state, 2006-2008: results from a new surveillance system

Background

HIV transmitted drug resistance (TDR) is a public health concern because it has the potential to compromise antiretroviral therapy (ART) at the population level. In New York State, high prevalence of TDR in a local cohort and a multiclass resistant case cluster led to the development and implementation of a statewide resistance surveillance system.

Methodology

We conducted a cross-sectional analysis of the 13,109 cases of HIV infection that were newly diagnosed and reported in New York State between 2006 and 2008, including 4,155 with HIV genotypes drawn within 3 months of initial diagnosis and electronically reported to the new resistance surveillance system. We assessed compliance with DHHS recommendations for genotypic resistance testing and estimated TDR among new HIV diagnoses.

Principal Findings

Of 13,109 new HIV diagnoses, 9,785 (75%) had laboratory evidence of utilization of HIV-related medical care, and 4,155 (43%) had a genotype performed within 3 months of initial diagnosis. Of these, 11.2% (95% confidence interval [CI], 10.2%–12.1%) had any evidence of TDR. The proportion with mutations associated with any antiretroviral agent in the NNRTI, NRTI or PI class was 6.3% (5.5%–7.0%), 4.3% (3.6%–4.9%) and 2.9% (2.4%–3.4%), respectively. Multiclass resistance was observed in <1%. TDR did not increase significantly over time (p for trend = 0.204). Men who have sex with men were not more likely to have TDR than persons with heterosexual risk factor (OR 1.0 (0.77–1.30)). TDR to EFV+TDF+FTC and LPV/r+TDF+FTC regimens was 7.1% (6.3%–7.9%) and 1.4% (1.0%–1.8%), respectively.

Conclusions/Significance

TDR appears to be evenly distributed and stable among new HIV diagnoses in New York State; multiclass TDR is rare. Less than half of new diagnoses initiating care received a genotype per DHHS guidelines.     

Not all are lost: interrupted laboratory monitoring, early death, and loss to follow-up (LTFU) in a large South African treatment program

Background

Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU). Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up.

Methods

We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART) in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM), defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes.

Results

In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39–0.62].

Conclusions

In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU.     

Adverse events among HIV/MDR-TB co-infected patients receiving antiretroviral and second line anti-TB treatment in Mumbai, India

Background

Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings.

Methods

Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE.

Results

Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen.

Conclusions

AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.     

Gender difference in 2-year mortality and immunological response to ART in an HIV-infected Chinese population, 2006-2008

Background

Since it was initiated in 2002, the China Free Antiretroviral Treatment (ART) Program has been progressing from an emergency response to a standardized treatment and care system. As of December 31, 2009, a total of 81,880 patients in 31 provinces, autonomous regions, and special municipalities received free ART. Gender differences, however, in mortality and immunological response to ART in this cohort have never been described.

Objective

To understand whether women and men who enrolled in the China National Free ART Program responded equally well to the treatment.

Methods

A retrospective analysis of the national free ART databases from June 2006–December 2008 was performed. HIV-infected subjects who were 18 years or older, ART naïve at baseline, and on a 3TC regimen enrolled in the program from June 1 to December 31, 2006, were included in this study, then followed up to 2 years.

Results

Among 3457 enrolled subjects who met the inclusion criteria, 59.2% were male and 40.8% female. The majority of the subjects were 19–44 years old (77%) and married (72%). Over the full 24 months of follow-up, the mortality rate was 19.0% in males and 11.4% in females (p = 0.0014). Males on therapy for 3–24 months were more likely to die than females (HR = 1.46, 95% CI: 1.04–2.06, p = 0.0307) after adjusting for baseline characteristics. Compared to men, women had higher CD4+ counts over time after initiating ART (p<0.0001).

Conclusions

Our study showed that women had an overall lower mortality and higher CD4+ counts than men in response to ART treatment, which may be attributed to adherence, biological factors, social, cultural and economic reasons. Further study is needed to explore these factors that might contribute to the gender differences in mortality and immunological response to ART.     

HIV-infected children in rural Zambia achieve good immunologic and virologic outcomes two years after initiating antiretroviral therapy

Background

Many HIV-infected children in sub-Saharan Africa reside in rural areas, yet most research on treatment outcomes has been conducted in urban centers. Rural clinics and residents may face unique barriers to care and treatment.

Methods

A prospective cohort study of HIV-infected children was conducted between September 2007 and September 2010 at the rural HIV clinic in Macha, Zambia. HIV-infected children younger than 16 years of age at study enrollment who received antiretroviral therapy (ART) during the study were eligible. Treatment outcomes during the first two years of ART, including mortality, immunologic status, and virologic suppression, were assessed and risk factors for mortality and virologic suppression were evaluated.

Results

A total of 69 children entered the study receiving ART and 198 initiated ART after study enrollment. The cumulative probabilities of death among children starting ART after study enrollment were 9.0% and 14.4% at 6 and 24 months after ART initiation. Younger age, higher viral load, lower CD4+ T-cell percentage and lower weight-for-age z-scores at ART initiation were associated with higher risk of mortality. The mean CD4⁺ T-cell percentage increased from 16.3% at treatment initiation to 29.3% and 35.0% at 6 and 24 months. The proportion of children with undetectable viral load increased to 88.5% and 77.8% at 6 and 24 months. Children with longer travel times (≥5 hours) and those taking nevirapine at ART initiation, as well as children who were non-adherent, were less likely to achieve virologic suppression after 6 months of ART.

Conclusions

HIV-infected children receiving treatment in a rural clinic experienced sustained immunologic and virologic improvements. Children with longer travel times were less likely to achieve virologic suppression, supporting the need for decentralized models of ART delivery.     

Diabetes with hypertension as risk factors for adult dengue hemorrhagic fever in a predominantly dengue serotype 2 epidemic: a case control study

Background

Dengue hemorrhagic fever (DHF) is a severe form of dengue, characterized by bleeding and plasma leakage. A number of DHF risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF. This study explored demographic and comorbidity risk factors for DHF in adult dengue epidemics in Singapore in year 2006 (predominantly serotype 1) and in year 2007–2008 (predominantly serotype 2).

Methods

A retrospective case-control study was conducted with 149 DHF and 326 dengue fever (DF) patients from year 2006, and 669 DHF and 1,141 DF patients from year 2007–2008. Demographic and reported comorbidity data were collected from patients previously. We performed multivariate logistic regression to assess the association between DHF and demographic and co-morbidities for year 2006 and year 2007–2008, respectively.

Results

Only Chinese (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.01–3.56) was independently associated with DHF in year 2006. In contrast, age groups of 30–39 years (AOR = 1.41; 95% CI:1.09–1.81), 40–49 years (AOR = 1.34; 95% CI:1.09–1.81), female (AOR = 1.57; 95% CI:1.28–1.94), Chinese (AOR = 1.67; 95% CI:1.24–2.24), diabetes (AOR = 1.78; 95% CI:1.06–2.97), and diabetes with hypertension (AOR = 2.16; 95%CI:1.18–3.96) were independently associated with DHF in year 2007–2008. Hypertension was proposed to have effect modification on the risk of DHF outcome in dengue patients with diabetes. Chinese who had diabetes with hypertension had 2.1 (95% CI:1.07–4.12) times higher risk of DHF compared with Chinese who had no diabetes and no hypertension.

Conclusions

Adult dengue patients in Singapore who were 30–49 years, Chinese, female, had diabetes or diabetes with hypertension were at greater risk of developing DHF during epidemic of predominantly serotype 2. These risk factors can be used to guide triaging of patients who require closer clinical monitoring and early hospitalization in Singapore, when confirmed in more studies.     

A comparison of initial antiretroviral therapy in the Swiss HIV Cohort Study and the recommendations of the International AIDS Society-USA

Background

In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS).

Methods

Initial ART regimens prescribed to participants between 1998 and 2007 were classified according to IAS-USA recommendations. Baseline characteristics of patients who received regimens in violation with these recommendations (violation ART) were compared to other patients. Multivariable logistic and linear regression analyses were performed to identify associations between violation ART and (i) virological suppression and (ii) CD4 cell count increase, after one year.

Results

Between 1998 and 2007, 4189 SHCS participants started 241 different ART regimens. A violation ART was started in 5% of patients. Female patients (adjusted odds ratio aOR 1.83, 95%CI 1.28–2.62), those with a high education level (aOR 1.49, 95%CI 1.07–2.06) or a high CD4 count (aOR 1.53, 95%CI 1.02–2.30) were more likely to receive violation ART. The proportion of patients with an undetectable viral load (<400 copies/mL) after one year was significantly lower with violation ART than with recommended regimens (aOR 0.54, 95% CI 0.37–0.80) whereas CD4 count increase after one year of treatment was similar in both groups.

Conclusions

Although more than 240 different initial regimens were prescribed, violations of the IAS-USA recommendations were uncommon. Patients receiving these regimens were less likely to have an undetectable viral load after one year, which strengthens the validity of these recommendations.     

Association of age with mortality and virological and immunological response to antiretroviral therapy in rural South African adults

Objective

To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort.

Design

Retrospective cohort analysis using data from a public HIV Treatment & Care Programme.

Methods

Adults initiating ART 1^st August 2004 - 31^st October 2009 were stratified by age at initiation: young adults (16–24 years) mid-age adults (25–49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points.

Results

8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25–49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90–7.78); 6.55 (95% CI 6.11–7.02) and 8.69 (95% CI 7.34–10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0–3 months (MR: 27.1 vs 17.17 and 21.36) and 3–12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0–3 months) whilst immunological and virological responses were associated with mortality after 12months.

Conclusions

Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART.     

HIV incidence and risk factors for acquisition in HIV discordant couples in Masaka, Uganda: an HIV vaccine preparedness study

Objectives

To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials.

Methods

HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months.

Results

495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1–6]; and 4.3 [2.8–6.4] and 4.4 [2.5–8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18–24 (aRR = 4.1, 95% CI 1.6–10.8) and 25–34 (aRR = 2.7, 95% CI 1.2–5.8) years]; alcohol use (aRR = 2.6, 95% CI 1.1–6); and reported genital discharge (aRR = 3.4, 95% CI 1.6–7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR = 0.4, 95% CI 0.2–0.8); always (aRR = 0.1, 95% CI 0.02–0.9)]. In the follow-up risk analysis, young age [18–24 (aRR = 6.2, 95% CI 2.2–17.3) and 25-34 (aRR = 2.3, 95% CI 1.1–5.0) years], reported genital discharge (aRR = 2.5, 95% CI 1.1–5.5), serological syphilis (aRR 3.2, 95% CI 1.3–7.7) and the partner being ART naïve (aRR = 4.8, 95% CI 1.4–16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study.

Conclusions

The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population.     

Hypertension in women of reproductive age in the United States: NHANES 1999-2008

Objective

To examine the epidemiology of hypertension in women of reproductive age.

Methods

Using NHANES from 1999–2008, we identified 5,521 women age 20–44 years old. Hypertension status was determined using blood pressure measurements and/or self-reported medication use.

Results

The estimated prevalence of hypertension in women of reproductive age was 7.7% (95% confidence interval (CI): 6.9%–8.5%). The prevalence of anti-hypertensive pharmacologic therapy was 4.2% (95% CI 3.5%–4.9%). The prevalence of hypertension was relatively stable across the study period; the age and race adjusted odds of hypertension in 2007–2008 did not differ significantly from 1999–2000 (odds ratio 1.2, CI 0.8 to 1.7, p = 0.45). Significant independent risk factors associated with hypertension included older age, non-Hispanic black race (compared to non-Hispanic whites), diabetes mellitus, chronic kidney disease, and higher body mass index. The most commonly used antihypertensive medications included diuretics, angiotensin-converting enzyme inhibitors (ACE), and beta blockers.

Conclusion

Hypertension occurs in about 8% of women of reproductive age. There are remarkable differences in the prevalence of hypertension between racial/ethnic groups. Obesity is a risk factor of particular importance in this population because it affects over 30% of young women in the U.S., is associated with more than 4 fold increased risk of hypertension, and is potentially modifiable.     

Population-level reduction in adult mortality after extension of free anti-retroviral therapy provision into rural areas in northern Malawi

Background

Four studies from sub-Saharan Africa have found a substantial population-level effect of ART provision on adult mortality. It is important to see if the impact changes with time since the start of treatment scale-up, and as treatment moves to smaller clinics.

Methods and Findings

During 2002-4 a demographic surveillance site (DSS) was established in Karonga district, northern Malawi. Information on births and deaths is collected monthly, with verbal autopsies conducted for all deaths; migrations are updated annually. We analysed mortality trends by comparing three time periods: pre-ART roll-out in the district (August 2002–June 2005), ART period 1 (July 2005–September 2006) when ART was available only in a town 70 km away, and ART period 2 (October 2006–September 2008), when ART was available at a clinic within the DSS area. HIV prevalence and ART uptake were estimated from a sero-survey conducted in 2007/2008. The all-cause mortality rate among 15–59 year olds was 10.2 per 1000 person-years in the pre-ART period (288 deaths/28285 person-years). It fell by 16% in ART period 1 and by 32% in ART period 2 (95% CI 18%–43%), compared with the pre-ART period. The AIDS mortality rate fell from 6.4 to 4.6 to 2.7 per 1000 person-years in the pre-ART period, period 1 and period 2 respectively (rate ratio for period 2 = 0.43, 95% CI 0.33–0.56). There was little change in non-AIDS mortality. Treatment coverage among individuals eligible to start ART was around 70% in 2008.

Conclusions

ART can have a dramatic effect on mortality in a resource-constrained setting in Africa, at least in the early years of treatment provision. Our findings support the decentralised delivery of ART from peripheral health centres with unsophisticated facilities. Continued funding to maintain and further scale-up treatment provision will bring large benefits in terms of saving lives.     

Treatment outcomes and cost-effectiveness of shifting management of stable ART patients to nurses in South Africa: an observational cohort

Background

To address human resource and infrastructure shortages, resource-constrained countries are being encouraged to shift HIV care to lesser trained care providers and lower level health care facilities. This study evaluated the cost-effectiveness of down-referring stable antiretroviral therapy (ART) patients from a doctor-managed, hospital-based ART clinic to a nurse-managed primary health care facility in Johannesburg, South Africa.

Methods and Findings

Criteria for down-referral were stable ART (≥11 mo), undetectable viral load within the previous 10 mo, CD4>200 cells/mm³, <5% weight loss over the last three visits, and no opportunistic infections. All patients down-referred from the treatment-initiation site to the down-referral site between 1 February 2008 and 1 January 2009 were compared to a matched sample of patients eligible for down-referral but not down-referred. Outcomes were assigned based on vital and health status 12 mo after down-referral eligibility and the average cost per outcome estimated from patient medical record data.The down-referral site (n = 712) experienced less death and loss to follow up than the treatment-initiation site (n = 2,136) (1.7% versus 6.2%, relative risk = 0.27, 95% CI 0.15–0.49). The average cost per patient-year for those in care and responding at 12 mo was US$492 for down-referred patients and US$551 for patients remaining at the treatment-initiation site (p<0.0001), a savings of 11%. Down-referral was the cost-effective strategy for eligible patients.

Conclusions

Twelve-month outcomes of stable ART patients who are down-referred to a primary health clinic are as good as, or better than, the outcomes of similar patients who are maintained at a hospital-based ART clinic. The cost of treatment with down-referral is lower across all outcomes and would save 11% for patients who remain in care and respond to treatment. These results suggest that this strategy would increase treatment capacity and conserve resources without compromising patient outcomes. Please see later in the article for the Editors'' Summary     

Early mortality and AIDS progression despite high initial antiretroviral therapy adherence and virologic suppression in Botswana

Background

Adverse outcomes occurring early after antiretroviral therapy (ART) initiation are common in sub-Saharan Africa, despite reports of high levels of ART adherence in this setting. We sought to determine the relationship between very early ART adherence and early adverse outcomes in HIV-infected adults in Botswana.

Methods

This prospective cohort study of 402 ART-naïve, HIV-infected adults initiating ART at a public HIV clinic in Gaborone, Botswana evaluated the relationship between suboptimal early ART adherence and HIV treatment outcomes in the initial months after ART initiation. Early adherence during the interval between initial ART dispensation and first ART refill was calculated using pill counts. In the primary analysis patients not returning to refill and those with adherence <0.95 were considered to have suboptimal early adherence. The primary outcome was death or loss to follow-up during the first 6 months of ART; a secondary composite outcome included the primary outcome plus incident opportunistic illness (OIs) and virologic failure. We also calculated the percent of early adverse outcomes theoretically attributable to suboptimal early adherence using the population attributable risk percent (PAR%).

Results

Suboptimal early adherence was independently associated with loss to follow-up and death (adjusted OR 2.3, 95% CI 1.1–4.8) and with the secondary composite outcome including incident OIs and virologic failure (adjusted OR 2.6, 95% CI 1.4–4.7). However, of those with early adverse outcomes, less than one-third had suboptimal adherence and approximately two-thirds achieved virologic suppression. The PAR% relating suboptimal early adherence and primary and secondary outcomes were 14.7% and 17.7%, respectively.

Conclusions

Suboptimal early adherence was associated with poor outcomes, but most early adverse outcomes occurred in patients with optimal early adherence. Clinical care and research efforts should focus on understanding early adverse outcomes that occur despite optimal adherence.