Voluntary medical male circumcision: logistics, commodities, and waste management requirements for scale-up of services

Background

The global HIV prevention community is implementing voluntary medical male circumcision (VMMC) programs across eastern and southern Africa, with a goal of reaching 80% coverage in adult males by 2015. Successful implementation will depend on the accessibility of commodities essential for VMMC programming and the appropriate allocation of resources to support the VMMC supply chain. For this, the United States President’s Emergency Plan for AIDS Relief, in collaboration with the World Health Organization and the Joint United Nations Programme on HIV/AIDS, has developed a standard list of commodities for VMMC programs.

Methods and Findings

This list of commodities was used to inform program planning for a 1-y program to circumcise 152,000 adult men in Swaziland. During this process, additional key commodities were identified, expanding the standard list to include commodities for waste management, HIV counseling and testing, and the treatment of sexually transmitted infections.The approximate costs for the procurement of commodities, management of a supply chain, and waste disposal, were determined for the VMMC program in Swaziland using current market prices of goods and services.Previous costing studies of VMMC programs did not capture supply chain costs, nor the full range of commodities needed for VMMC program implementation or waste management. Our calculations indicate that depending upon the volume of services provided, supply chain and waste management, including commodities and associated labor, contribute between US$58.92 and US$73.57 to the cost of performing one adult male circumcision in Swaziland.

Conclusions

Experience with the VMMC program in Swaziland indicates that supply chain and waste management add approximately US$60 per circumcision, nearly doubling the total per procedure cost estimated previously; these additional costs are used to inform the estimate of per procedure costs modeled by Njeuhmeli et al. in “Voluntary Medical Male Circumcision: Modeling the Impact and Cost of Expanding Male Circumcision for HIV Prevention in Eastern and Southern Africa.” Program planners and policy makers should consider the significant contribution of supply chain and waste management to VMMC program costs as they determine future resource needs for VMMC programs. Please see later in the article for the Editors'' Summary     

Recent Patterns in Population-Based HIV Prevalence in Swaziland

Background

The 2011 Swaziland HIV Incidence Measurement Survey (SHIMS) was conducted as part of a national study to evaluate the scale up of key HIV prevention programs.

Methods

From a randomly selected sample of all Swazi households, all women and men aged 18-49 were considered eligible, and all consenting adults were enrolled and received HIV testing and counseling. In this analysis, population-based measures of HIV prevalence were produced and compared against similarly measured HIV prevalence estimates from the 2006-7 Swaziland Demographic and Health. Also, measures of HIV service utilization in both HIV infected and uninfected populations were documented and discussed.

Results

HIV prevalence among adults aged 18-49 has remained unchanged between 2006-2011 at 31-32%, with substantial differences in current prevalence between women (39%) and men (24%). In both men and women, between since 2006-7 and 2011, prevalence has fallen in the young age groups and risen in the older age groups. Over a third (38%) of the HIV-infected population was unaware of their infection status, and this differed markedly between men (50%) and women (31%). Of those aware of their HIV-positive status, a higher percentage of men (63%) than women (49%) reported ART use.

Conclusions

While overall HIV prevalence remains roughly constant, age-specific changes strongly suggest both improved survival of the HIV-infected and a reduction in new HIV infections. Awareness of HIV status and entry into ART services has improved in recent years but remains too low. This study identifies opportunities to improve both HIV preventive and care services in Swaziland.     

Effectiveness and cost effectiveness of expanding harm reduction and antiretroviral therapy in a mixed HIV epidemic: a modeling analysis for Ukraine

Background

Injection drug use (IDU) and heterosexual virus transmission both contribute to the growing mixed HIV epidemics in Eastern Europe and Central Asia. In Ukraine—chosen in this study as a representative country—IDU-related risk behaviors cause half of new infections, but few injection drug users (IDUs) receive methadone substitution therapy. Only 10% of eligible individuals receive antiretroviral therapy (ART). The appropriate resource allocation between these programs has not been studied. We estimated the effectiveness and cost-effectiveness of strategies for expanding methadone substitution therapy programs and ART in mixed HIV epidemics, using Ukraine as a case study.

Methods and Findings

We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs using opiates, and IDUs on methadone substitution therapy, stratified by HIV status, and populated it with data from the Ukraine. We considered interventions expanding methadone substitution therapy, increasing access to ART, or both. We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, infections averted, and incremental cost-effectiveness. Without incremental interventions, HIV prevalence reached 67.2% (IDUs) and 0.88% (non-IDUs) after 20 years. Offering methadone substitution therapy to 25% of IDUs reduced prevalence most effectively (to 53.1% IDUs, 0.80% non-IDUs), and was most cost-effective, averting 4,700 infections and adding 76,000 QALYs compared with no intervention at US$530/QALY gained. Expanding both ART (80% coverage of those eligible for ART according to WHO criteria) and methadone substitution therapy (25% coverage) was the next most cost-effective strategy, adding 105,000 QALYs at US$1,120/QALY gained versus the methadone substitution therapy-only strategy and averting 8,300 infections versus no intervention. Expanding only ART (80% coverage) added 38,000 QALYs at US$2,240/QALY gained versus the methadone substitution therapy-only strategy, and averted 4,080 infections versus no intervention. Offering ART to 80% of non-IDUs eligible for treatment by WHO criteria, but only 10% of IDUs, averted only 1,800 infections versus no intervention and was not cost effective.

Conclusions

Methadone substitution therapy is a highly cost-effective option for the growing mixed HIV epidemic in Ukraine. A strategy that expands both methadone substitution therapy and ART to high levels is the most effective intervention, and is very cost effective by WHO criteria. When expanding ART, access to methadone substitution therapy provides additional benefit in infections averted. Our findings are potentially relevant to other settings with mixed HIV epidemics. Please see later in the article for the Editors'' Summary     

Integrating prevention of mother-to-child HIV transmission programs to improve uptake: a systematic review

Background

We performed a systematic review to assess the effect of integrated perinatal prevention of mother-to-child transmission of HIV interventions compared to non- or partially integrated services on the uptake in low- and middle-income countries.

Methods

We searched for experimental, quasi-experimental and controlled observational studies in any language from 21 databases and grey literature sources.

Results

Out of 28 654 citations retrieved, five studies met our inclusion criteria. A cluster randomized controlled trial reported higher probability of nevirapine uptake at the labor wards implementing HIV testing and structured nevirapine adherence assessment (RRR 1.37, bootstrapped 95% CI, 1.04–1.77). A stepped wedge design study showed marked improvement in antiretroviral therapy (ART) enrolment (44.4% versus 25.3%, p<0.001) and initiation (32.9% versus 14.4%, p<0.001) in integrated care, but the median gestational age of ART initiation (27.1 versus 27.7 weeks, p = 0.4), ART duration (10.8 versus 10.0 weeks, p = 0.3) or 90 days ART retention (87.8% versus 91.3%, p = 0.3) did not differ significantly. A cohort study reported no significant difference either in the ART coverage (55% versus 48% versus 47%, p = 0.29) or eight weeks of ART duration before the delivery (50% versus 42% versus 52%; p = 0.96) between integrated, proximal and distal partially integrated care. Two before and after studies assessed the impact of integration on HIV testing uptake in antenatal care. The first study reported that significantly more women received information on PMTCT (92% versus 77%, p<0.001), were tested (76% versus 62%, p<0.001) and learned their HIV status (66% versus 55%, p<0.001) after integration. The second study also reported significant increase in HIV testing uptake after integration (98.8% versus 52.6%, p<0.001).

Conclusion

Limited, non-generalizable evidence supports the effectiveness of integrated PMTCT programs. More research measuring coverage and other relevant outcomes is urgently needed to inform the design of services delivering PMTCT programs.     

Comparison of methods to correct survival estimates and survival regression analysis on a large HIV African cohort

Objective

The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses.

Methods

We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis.

Results

Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76–1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61–2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17–1.66 vs. 1.29 to 1.34).

Conclusions

In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.     

Retention in care and connection to care among HIV-infected patients on antiretroviral therapy in Africa: estimation via a sampling-based approach

Introduction

Current estimates of retention among HIV-infected patients on antiretroviral therapy (ART) in Africa consider patients who are lost to follow-up (LTF) as well as those who die shortly after their last clinic visit to be no longer in care and to represent limitations in access to care. Yet many lost patients may have “silently” transferred and deaths shortly after the last clinic visit more likely represent limitations in clinical care rather than access to care after initial linkage.

Methods

We evaluated HIV-infected adults initiating ART from 1/1/2004 to 9/30/2007 at a clinic in rural Uganda. A representative sample of lost patients was tracked in the community to obtain updated information about care at other ART sites. Updated outcomes were incorporated with probability weights to obtain “corrected” estimates of retention for the entire clinic population. We used the competing risks approach to estimate “connection to care”—the percentage of patients accessing care over time (including those who died while in care).

Results

Among 3,628 patients, 829 became lost, 128 were tracked and in 111, updated information was obtained. Of 111, 79 (71%) were alive and 35/48 (73%) of patients interviewed in person were in care and on ART. Patient retention for the clinic population assuming lost patients were not in care was 82.3%, 68.9%, and 60.1% at 1, 2 and 3 years. Incorporating updated care information from the sample of lost patients increased estimates of patient retention to 85.8% to 90.9%, 78.9% to 86.2% and 75.8% to 84.7% at the same time points.

Conclusions

Accounting for “silent transfers” and early deaths increased estimates of patient retention and connection to care substantially. Deaths soon after the last clinic visit (potentially reflecting limitations in clinical effectiveness) and disconnection from care among patient who were alive each accounted for approximately half of failures of retention.     

Quality of Life Outcomes of Antiretroviral Treatment for HIV/AIDS Patients in Vietnam

Objective

This study assessed health-related quality of life (HRQOL) and its related factors in HIV/AIDS patients taking antiretroviral treatment (ART) in Vietnam.

Methods

A cross-sectional study was conducted with 1016 patients (36.2% women, mean age = 35.4) in three epicenters of Vietnam, including Hanoi, Hai Phong, and Ho Chi Minh City. HRQOL was assessed using the Vietnamese version of the WHOQOL-HIV BREF. Factor analysis classified measure items into six HRQOL dimensions, namely Physical, Morbidity, Social, Spirituality, Performance, and Environment. Tobit censored regression models were applied to determine associations of patient’s characteristics and HRQOL domain scores.

Results

Internal consistency reliability of the six domains ranged from 0.69 to 0.89. The WHOQOL-HIV BREF had a good discriminative validity with patient’s disease stages, CD4 cell counts, and duration of ART. In a band score of (4, 20), six domains were moderate; “Environment” had the highest score (13.8±2.8), and “Social” had the lowest score (11.2±3.3). Worse HRQOL were observed in patients at provincial and district clinics. Those patients who were male, had higher educational attainment, and are employed, reported better HRQOL. In reduced regression models, poorer HRQOL was found in patients who had advanced HIV infection and had CD4 cell count <200 cells/mL. Patients reported significantly poorer Physical and Social in the 1^st year ART, but moderately better Performance, Morbidity, Spirituality, and Environment from the 2^nd year ART, compared to those not-yet-on ART.

Conclusion

Strengthening the quality of ART services at the provincial and district levels, gender-specific impact mitigation, and early treatment supports are recommended for further expansion of ART services in Vietnam. Regular assessments of HRQOL may provide important indicators for monitoring and evaluating HIV/AIDS services.     

WHO 2010 guidelines for prevention of mother-to-child HIV transmission in Zimbabwe: modeling clinical outcomes in infants and mothers

Background

The Zimbabwean national prevention of mother-to-child HIV transmission (PMTCT) program provided primarily single-dose nevirapine (sdNVP) from 2002–2009 and is currently replacing sdNVP with more effective antiretroviral (ARV) regimens.

Methods

Published HIV and PMTCT models, with local trial and programmatic data, were used to simulate a cohort of HIV-infected, pregnant/breastfeeding women in Zimbabwe (mean age 24.0 years, mean CD4 451 cells/µL). We compared five PMTCT regimens at a fixed level of PMTCT medication uptake: 1) no antenatal ARVs (comparator); 2) sdNVP; 3) WHO 2010 guidelines using “Option A” (zidovudine during pregnancy/infant NVP during breastfeeding for women without advanced HIV disease; lifelong 3-drug antiretroviral therapy (ART) for women with advanced disease); 4) WHO “Option B” (ART during pregnancy/breastfeeding without advanced disease; lifelong ART with advanced disease); and 5) “Option B+:” lifelong ART for all pregnant/breastfeeding, HIV-infected women. Pediatric (4–6 week and 18-month infection risk, 2-year survival) and maternal (2- and 5-year survival, life expectancy from delivery) outcomes were projected.

Results

Eighteen-month pediatric infection risks ranged from 25.8% (no antenatal ARVs) to 10.9% (Options B/B+). Although maternal short-term outcomes (2- and 5-year survival) varied only slightly by regimen, maternal life expectancy was reduced after receipt of sdNVP (13.8 years) or Option B (13.9 years) compared to no antenatal ARVs (14.0 years), Option A (14.0 years), or Option B+ (14.5 years).

Conclusions

Replacement of sdNVP with currently recommended regimens for PMTCT (WHO Options A, B, or B+) is necessary to reduce infant HIV infection risk in Zimbabwe. The planned transition to Option A may also improve both pediatric and maternal outcomes.     

Inaccurate Diagnosis of HIV-1 Group M and O Is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon

Background

Increased access to HIV testing is essential in working towards universal access to HIV prevention and treatment in resource-limited countries. We here evaluated currently used HIV diagnostic tests and algorithms in Cameroon for their ability to correctly identify HIV infections.

Methods

We estimated sensitivity, specificity, and positive and negative predictive values of 5 rapid/simple tests, of which 3 were used by the national program, and 2 fourth generation ELISAs. The reference panel included 500 locally collected samples; 187 HIV -1 M, 10 HIV-1 O, 259 HIV negative and 44 HIV indeterminate plasmas.

Results

None of the 5 rapid assays and only 1 ELISA reached the current WHO/UNAIDS recommendations on performance of HIV tests of at least 99% sensitivity and 98% specificity. Overall, sensitivities ranged between 94.1% and 100%, while specificities were 88.0% to 98.8%. The combination of all assays generated up to 9% of samples with indeterminate HIV status, because they reacted discordantly with at least one of the different tests. Including HIV indeterminate samples in test efficiency calculations significantly decreased specificities to a range from 77.9% to 98.0%. Finally, two rapid assays failed to detect all HIV-1 group O variants tested, with one rapid test detecting only 2 out of 10 group O specimens.

Conclusion

In the era of ART scaling-up in Africa, significant proportions of false positive but also false negative results are still observed with HIV screening tests commonly used in Africa, resulting in inadequate treatment and prevention strategies. Depending on tests or algorithms used, up to 6% of HIV-1 M and 80% of HIV-1 O infected patients in Cameroon do not receive ART and adequate counseling to prevent further transmission due to low sensitivities. Also, the use of tests with low specificities could imply inclusion of up to 12% HIV negative people in ART programs and increase budgets in addition to inconveniences caused to patients.     

Long-term adherence to antiretroviral treatment and program drop-out in a high-risk urban setting in sub-Saharan Africa: a prospective cohort study

Background

Seventy percent of urban populations in sub-Saharan Africa live in slums. Sustaining HIV patients in these high-risk and highly mobile settings is a major future challenge. This study seeks to assess program retention and to find determinants for low adherence to antiretroviral treatment (ART) and drop-out from an established HIV/ART program in Kibera, Nairobi, one of Africa''s largest informal urban settlements.

Methods and Findings

A prospective open cohort study of 800 patients was performed at the African Medical Research Foundation (AMREF) clinic in the Kibera slum. Adherence to ART and drop-out from the ART program were independent outcomes. Two different adherence measures were used: (1) “dose adherence” (the proportion of a prescribed dose taken over the past 4 days) and (2) “adherence index” (based on three adherence questions covering dosing, timing and special instructions). Drop-out from the program was calculated based on clinic appointment dates and number of prescribed doses, and a patient was defined as being lost to follow-up if over 90 days had expired since the last prescribed dose. More than one third of patients were non-adherent when all three aspects of adherence – dosing, timing and special instructions – were taken into account. Multivariate logistic regression revealed that not disclosing HIV status, having a low level of education, living below the poverty limit (US$ 2/day) and not having a treatment buddy were significant predictors for non-adherence. Additionally, one quarter of patients dropped out for more than 90 days after the last prescribed ART dose. Not having a treatment buddy was associated with increased risk for drop-out (hazard ratio 1.4, 95% CI = 1.0–1.9).

Conclusion

These findings point to the dilemma of trying to sustain a growing number of people on life-long ART in conditions where prevailing stigma, poverty and food shortages threatens the long-term success of HIV treatment.     

Evaluating the cost-effectiveness of pre-exposure prophylaxis (PrEP) and its impact on HIV-1 transmission in South Africa

Background

Mathematical modelers have given little attention to the question of how pre-exposure prophylaxis (PrEP) may impact on a generalized national HIV epidemic and its cost-effectiveness, in the context of control strategies such as condom use promotion and expanding ART programs.

Methodology/Principal Findings

We use an age- and gender-structured model of the generalized HIV epidemic in South Africa to investigate the potential impact of PrEP in averting new infections. The model utilizes age-structured mortality, fertility, partnership and condom use data to model the spread of HIV and the shift of peak prevalence to older age groups. The model shows that universal PrEP coverage would have to be impractically high to have a significant effect on incidence reduction while ART coverage expands. PrEP targeted to 15–35-year-old women would avert 10%–25% (resp. 13%–28%) of infections in this group and 5%–12% (resp. 7%–16%) of all infections in the period 2014–2025 if baseline incidence is 0.5% per year at 2025 (resp. 0.8% per year at 2025). The cost would be $12,500–$20,000 per infection averted, depending on the level of ART coverage and baseline incidence. An optimistic scenario of 30%–60% PrEP coverage, efficacy of at least 90%, no behavior change among PrEP users and ART coverage less than three times its 2010 levels is required to achieve this result. Targeting PrEP to 25–35-year-old women (at highest risk of infection) improves impact and cost-effectiveness marginally. Relatively low levels of condom substitution (e.g., 30%) do not nullify the efficacy of PrEP, but reduces cost-effectiveness by 35%–40%.

Conclusions/Significance

PrEP can avert as many as 30% of new infections in targeted age groups of women at highest risk of infection. The cost-effectiveness of PrEP relative to ART decreases rapidly as ART coverage increases beyond three times its coverage in 2010, after which the ART program would provide coverage to more than 65% of HIV₊ individuals. To have a high relative cost-effective impact on reducing infections in generalized epidemics, PrEP must utilize a window of opportunity until ART has been scaled up beyond this level.     

Combining qualitative and quantitative evidence to determine factors leading to late presentation for antiretroviral therapy in Malawi

Background

Treatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa.

Objective

To better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi.

Methods

Qualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009.

Results

43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women''s frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men''s commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3–3.9) and never being married (adjusted OR 4.1, 95% CI1.5–11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15–0.63),compared to those with no dependent children.

Conclusion

Gender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.     

Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa

Background

Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART.

Methodology

Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis.

Findings

Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period.

Conclusion

Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.     

Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050

Background

Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa.

Methods

We model a best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm³ (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011–2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses.

Results

Expanding ART to CD4 count <350 cells/mm³ prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9–194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%.

Conclusion

Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.     

Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection

Objectives

The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI).

Design

Two populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450) trials.

Methods

Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences in pVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression. Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimated through a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop.

Results

Of 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48–51) weeks after stopping ART. Four weeks after stopping treatment, although the proportion with pVL≥400 copies/ml was similar (78% PHI versus 79% CHI), levels were 0.45 (95% CI 0.26–0.64) log₁₀ copies/ml lower for PHI versus CHI, and remained lower up to 48 weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir >500 cells/mm³ was comparable to that experienced by PHI participants.

Conclusions

Stopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increased transmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.     

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.     

Understanding the Potential Impact of a Combination HIV Prevention Intervention in a Hyper-Endemic Community

Objectives

Despite demonstrating only partial efficacy in preventing new infections, available HIV prevention interventions could offer a powerful strategy when combined. In anticipation of combination HIV prevention programs and research studies we estimated the population-level impact of combining effective scalable interventions at high population coverage, determined the factors that influence this impact, and estimated the synergy between the components.

Methods

We used a mathematical model to investigate the effect on HIV incidence of a combination HIV prevention intervention comprised of high coverage of HIV testing and counselling, risk reduction following HIV diagnosis, male circumcision for HIV-uninfected men, and antiretroviral therapy (ART) for HIV-infected persons. The model was calibrated to data for KwaZulu-Natal, South Africa, where adult HIV prevalence is approximately 23%.

Results

Compared to current levels of HIV testing, circumcision, and ART, the combined intervention with ART initiation according to current guidelines could reduce HIV incidence by 47%, from 2.3 new infections per 100 person-years (pyar) to 1.2 per 100 pyar within 4 years and by almost 60%, to 1 per 100 pyar, after 25 years. Short-term impact is driven primarily by uptake of testing and reductions in risk behaviour following testing while long-term effects are driven by periodic HIV testing and retention in ART programs. If the combination prevention program incorporated HIV treatment upon diagnosis, incidence could be reduced by 63% after 4 years and by 76% (to about 0.5 per 100 pyar) after 15 years. The full impact of the combination interventions accrues over 10–15 years. Synergy is demonstrated between the intervention components.

Conclusion

High coverage combination of evidence-based strategies could generate substantial reductions in population HIV incidence in an African generalized HIV epidemic setting. The full impact could be underestimated by the short assessment duration of typical evaluations.     

Risk behaviors and reasons for not getting tested for HIV among men who have sex with men: an online survey in Peru

Background

Men who have sex with men (MSM) account for the greatest burden of the HIV epidemic in Peru. Given that MSM are frequent users of the Internet, understanding the risk behaviors and the reasons for not getting tested among MSM who surf the Internet may improve the tailoring of future online behavioral interventions.

Methods

From October 2007 to April 2008, we conducted an online survey among users of seven Peruvian gay websites.

Results

We received 1,481 surveys, 1,301 of which were included in the analysis. The median age of the participants was 22.5 years (range 12 – 71), 67% were homosexual, and the remainder was bisexual. Of survey respondents, 49.4% had never been tested for HIV and only 11.3% were contacted in-person during the last year by peer health educators from the Peruvian Ministry of Health and NGOs. Additionally, 50.8% had unprotected anal or vaginal sex at last intercourse, and a significant percentage reported a condom broken (22.1%), slipped (16.4%) or sexual intercourse initiated without wearing a condom (39.1%). The most common reasons for not getting tested for HIV among high-risk MSM were “I fear the consequences of a positive test result” (n = 55, 34.4%), and “I don''t know where I can get tested” (n = 50, 31.3%).

Conclusions

A small percentage of Peruvian MSM who answered our online survey, were reached by traditional peer-based education programs. Given that among high-risk MSM, fear of a positive test result and lack of awareness of places where to get tested are the most important reasons for not taking an HIV test, Internet interventions aimed at motivating HIV testing should work to reduce fear of testing and increase awareness of places that offer free HIV testing services to MSM.     

Rising population cost for treating people living with HIV in the UK, 1997-2013

Background

The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997–2006 and projected them 2007–2013.

Methods

Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices). Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997–2006 and projected 2007–2013.

Results

Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013.

Conclusions

Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV''s longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources.     

Presentation and outcome of tuberculous meningitis in a high HIV prevalence setting

Background

Mycobacterium tuberculosis is a common, devastating cause of meningitis in HIV-infected persons. Due to international rollout programs, access to antiretroviral therapy (ART) is increasing globally. Starting patients with HIV-associated tuberculous meningitis (TBM) on ART during tuberculosis (TB) treatment may increase survival in these patients. We undertook this study to describe causes of meningitis at a secondary-level hospital in a high HIV/TB co-infection setting and to determine predictors of mortality in patients with TBM.

Methods

A retrospective review of cerebrospinal fluid findings and clinical records over a six-month period (March 2009–August 2009). Definite, probable and possible TBM were diagnosed according to published case definitions.

Results

TBM was diagnosed in 120/211 patients (57%) with meningitis. In 106 HIV-infected patients with TBM, six-month all-cause mortality was lower in those who received antiretroviral therapy (ART) during TB treatment; hazard ratio = 0.30 (95% CI = 0.08–0.82). Factors associated with inpatient mortality in HIV-infected patients were 1) low CD4⁺ count at presentation; adjusted odds ratio (AOR) = 1.4 (95% confidence interval [CI] = 1.03–1.96) per 50 cells/µL drop in CD4⁺ count and, 2) higher British Medical Research Council TBM disease grade (2 or 3 versus 1); AOR = 4.8 (95% CI = 1.45–15.87).

Interpretation

Starting ART prior to or during TB treatment may be associated with lower mortality in patients with HIV-associated TBM. Advanced HIV and worse stage of TBM disease predict in-hospital mortality in patients presenting with TBM.