Reduced referral and case fatality rates for severe symptomatic hyperlactataemia in a South African public sector antiretroviral programme: a retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Interventions to promote prevention and earlier diagnosis of severe symptomatic hyperlactataemia (SHL) were implemented in the Western Cape provincial antiretroviral programme (South Africa) from 2004. Interventions included clinician education, point-of-care lactate meters, switch from stavudine to zidovudine in high risk patients and stavudine dose reduction. This study assessed trends in referral rate, severity at presentation and case fatality rate for severe SHL.</p> <p>Methods</p> <p>Retrospective study of severe SHL cases diagnosed at a referral facility from 1 January 2003 to 31 December 2008. Severe SHL was defined as patients with compatible symptoms and serum lactate ≥ 5 mmol/l attributable to antiretroviral therapy (ART). Cumulative ART exposure at referring ART clinics was used to calculate referral rates.</p> <p>Results</p> <p>There were 254 severe SHL cases. The referral rate (per thousand patient years [py] ART exposure) peaked in 2005 (20.4/1000py), but fell to 1.3/1000py by 2008 (incidence rate ratio [IRR] = 0.07, 95%CI 0.04-0.11). In 2003, 66.7% of cases presented with a standard bicarbonate (SHCO₃) level <15 mmol/l, but this fell to 12.5% by 2008 (p for trend < 0.001). Case fatality rate fell from a peak of 33.3% in 2004 to 0% in 2008 (p for trend = 0.002).</p> <p>Conclusions</p> <p>These trends suggest the interventions were associated with reduced referral, less severe metabolic acidosis at presentation and improved survival.</p

Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: The role of inadequate secondary prophylaxis

Objectives. Cryptococcal meningitis is the most common cause of adult meningitis in southern Africa. Much of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We studied the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal meningitis. Design. A prospective observational study of patients presenting with laboratory-confirmed symptomatic relapse of HIV-associated cryptococcal meningitis between January 2007 and December 2008 at GF Jooste Hospital, a public sector adult referral hospital in Cape Town. Outcome measures. Relapse episodes were categorised into: (i) patients not taking fluconazole prophylaxis; (ii) immune reconstitution inflammatory syndrome (IRIS); and (iii) relapses occurring prior to ART in patients taking fluconazole. In-hospital mortality was recorded. Results. There were 69 relapse episodes, accounting for 23% of all cases of cryptococcal meningitis; 43% (N=30) of relapse episodes were in patients not receiving fluconazole prophylaxis, 45% (N=31) were due to IRIS, and 12% (N=8) were in patients pre-ART taking fluconazole. Patients developing relapse due to inadequate secondary prophylaxis had severe disease and high in-hospital mortality (33%). Of the 30 patients not taking fluconazole, 47% (N=14) had not been prescribed secondary prophylaxis by their health care providers. We documented no relapses due to fluconazole resistance in these patients who received amphotericin B as initial therapy. Conclusions. A large number of relapses of cryptococcal meningitis are due to failed prescription, dispensing and referral for or adherence to secondary fluconazole prophylaxis. Interventions to improve the use of secondary fluconazole prophylaxis are essential

Symptomatic relapse of HIV-associated cryptococcal meningitis in South Africa: the role of inadequate secondary prophylaxis.

OBJECTIVES: Cryptococcal meningitis is the commonest cause of adult meningitis in Southern Africa. A sizeable proportion of this disease burden is thought to be due to symptomatic relapse of previously treated infection. We carried out a study to examine the contribution of inadequate secondary fluconazole prophylaxis to symptomatic relapses of cryptococcal meningitis. DESIGN: A prospective observational study of patients presenting with laboratory-confirmed symptomatic relapse of HIV-associated cryptococcal meningitis between January 2007 and December 2008 at GF Jooste Hospital, a public sector adult referral hospital in Cape Town. OUTCOME MEASURES: Relapse episodes were categorized into 1) patients not taking fluconazole prophylaxis, 2) immune reconstitution inflammatory syndrome (IRIS) and 3) relapses occurring prior to ART in patients taking fluconazole. In-hospital mortality was recorded. RESULTS: There were 69 relapse episodes, accounting for 23% of all cases of cryptococcal meningitis. 43%(n=30) of relapse episodes were in patients not taking fluconazole prophylaxis, 45%(31) were due to IRIS and 12%(8) were in patients pre-ART taking fluconazole. Patients developing relapse due to inadequate secondary prophylaxis had severe disease and high in-hospital mortality (33%). Of the 30 patients not taking fluconazole, 47% (14) had not been prescribed secondary prophylaxis by their healthcare providers. Importantly, we documented no relapses due to fluconazole resistance in this cohort of patients who has received amphotericin B as initial therapy. CONCLUSIONS: Large numbers of relapses of cryptococcal meningitis are due to failed prescription, dispensing, referral for or adherence to secondary fluconazole prophylaxis. Interventions to improve the use of secondary fluconazole prophylaxis are essential

Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial.

BACKGROUND: Interferon-gamma (IFNγ) is of key importance in the immune response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis remains high, and novel treatment strategies are needed. We performed a randomized controlled trial to determine whether addition of IFNγ to standard therapy increased the rate of clearance of cryptococcal infection in HIV-associated cryptococcal meningitis. METHODS: Patients were randomized to amphotericin B 1 mg/kg per day and 5FC 100 mg/kg per day for 2 weeks (standard therapy), standard therapy and IFNγ1b 100 μg days 1 and 3 (IFNγ two doses), or standard therapy and IFNγ1b 100 μg days 1, 3, 5, 8, 10 and 12 (IFNγ six doses). Primary outcome was rate of clearance of cryptococcus from the cerebrospinal fluid (CSF) (early fungicidal activity, EFA) calculated from serial quantitative cultures, previously shown to be independently associated with survival. RESULTS: Rate of fungal clearance was significantly faster in IFNγ containing groups than with standard treatment. Mean EFA [log colony forming unit (CFU)/ml per day] was -0.49 with standard treatment, -0.64 with IFNγ two doses, and -0.64 with IFNγ six doses. Difference in EFA was -0.15 [confidence interval (95% CI) -0.02 to -0.27, P=0.02] between standard treatment and IFNγ two doses, and -0.15 (95% CI -0.05 to -0.26, P=0.006) between standard treatment and IFNγ six doses. Mortality was 16% (14/88) at 2 weeks and 31% (27/87) at 10 weeks, with no significant difference between groups. All treatments were well tolerated. CONCLUSION: Addition of short-course IFNγ to standard treatment significantly increased the rate of clearance of cryptococcal infection from the CSF, and was not associated with any increase in adverse events. Two doses of IFNγ are as effective as six doses

Towards 'men who have sex with menappropriate' health services in South Africa

Health programming for men who have sex with men (MSM) in South Africa has been ignored or absent until fairly recently, despite this population being at high risk for HIV acquisition and transmission. Anova Health Institute, with support from the US President's Emergency Plan for AIDS Relief (PEPFAR)/United States Agency for International Development (USAID) and in collaboration with the South African National Department of Health, launched the first state sector MSM-targeted sexual health clinic in 2010. The clinic has been successful in attracting and retaining MSM in care, and lessons learned are described in this article. Components contributing to the creation of MSM-appropriate healthcare services are discussed

A cross sectional analysis of Gonococcal and Chlamydial infections among men-who-have-sex-with-men in Cape Town, South Africa

BACKGROUND: Men-who-have-sex-with-men (MSM) are at high risk of HIV and sexually transmitted infection (STI) transmission. Asymptomatic STIs are common in MSM and remain undiagnosed and untreated where syndromic management is advocated. Untreated STIs could be contributing to high HIV rates. This study investigated symptomatic (SSTI) and asymptomatic STIs (ASTIs) in MSM in Cape Town. METHODS: MSM, 18 years and above, were enrolled into this study. Participants underwent clinical and microbiological screening for STIs. Urine, oro-pharyngeal and anal swab specimens were collected for STI analysis, and blood for HIV and syphilis screening. A psychosocial and sexual questionnaire was completed. STI specimens were analysed for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infection. RESULTS: 200 MSM were recruited with a median age of 32 years (IQR 26-39.5). Their median number of sex partners within the last year was 5 (IQR 2-20). 155/200 (78%) reported only male sex partners while 45/200 (23%) reported sex with men and women. 77/200 (39%) reported transactional sex. At enrolment, 88/200 (44%) were HIV positive and 8/112 (7%) initially HIV-negative participants seroconverted during the study. Overall, 47/200 (24%) screened positive for either NG or CT. There were 32 MSM (16%) infected with NG and 7 (3.5%) of these men had NG infections at two anatomical sites (39 NG positive results in total). Likewise, there were 23 MSM (12%) infected with CT and all these men had infections at only one site. Eight of the 47 men (17%) were infected with both NG and CT. ASTI was more common than SSTI irrespective of anatomical site, 38 /200 (19%) versus 9/200 (5%) respectively (p<0.001). The anus was most commonly affected, followed by the oro-pharynx and then urethra. Asymptomatic infection was associated with transgender identity (OR 4.09 CI 1.60-5.62), ≥5 male sex partners in the last year (OR 2.50 CI 1.16-5.62) and transactional sex (OR 2.33 CI 1.13-4.79) but not with HIV infection. CONCLUSIONS: Asymptomatic STI was common and would not have been detected using a syndromic management approach. Although molecular screening for NG/CT is costly, in our study only four MSM needed to be screened to detect one case. This supports dual NG/CT molecular screening for MSM, which, in the case of confirmed NG infections, may trigger further culture-based investigations to determine gonococcal antimicrobial susceptibility in the current era of multi-drug resistant gonorrhoea

Clinical and financial burdens of secondary level care in a public sector antiretroviral roll-out setting (G F Jooste Hospital)

Background: Antiretroviral therapy (ART) is being extended across South Africa. While efforts have been made to assess the costs of providing ART via accredited service points, little information is available on its downstream costs, particularly in public secondary level hospitals. Objectives: To determine the cost of care for inpatients and outpatients at a dedicated antiretroviral referral unit treating and caring for antiretroviral-related conditions in a South African peri-urban setting; to identify key epidemiological cost drivers; and to examine the associated clinical and outcome data. Methods: A prospective costing study on 48 outpatients and 25 inpatients was conducted from a health system perspective. Incremental economic costs and clinical data were collected from primary sources at G F Jooste Hospital, Cape Town, over a 1-month period (March 2005). Results: Incremental cost per outpatient was R1 280, and per inpatient R5 802. Costs were dominated by medical staff costs (62% inpatient and 58% outpatient, respectively). Infections predominated among diagnoses and costs – 55% and 67% respectively for inpatients, and 49% and 54% respectively for outpatients. Most inpatients and outpatients were judged by attending physicians to have improved or stabilised as a result of treatment (52% and 59% respectively). Conclusions. The costs of providing secondary level care for patients on or immediately preceding ART initiation can be significant and should be included in the government’s strategic planning: (i) so that the service can be expanded to meet current and future needs; and (ii) to avoid crowding out other secondary level health services

Detectable HIV-1 in semen in individuals with very low blood viral loads

Abstract Background Several reports indicate that a portion (5–10%) of men living with HIV-1 intermittently shed HIV-1 RNA into seminal plasma while on long term effective antiretroviral therapy (ART). This is highly suggestive of an HIV-1 reservoir in the male genital tract. However, the status of this reservoir in men living with HIV-1 who are not under treatment is underexplored and has implications for understanding the origins and evolution of the reservoir. Finding Forty-three HIV-1 positive, antiretroviral therapy naïve study participants attending a men’s health clinic were studied. Semen viral loads and blood viral loads were generally correlated, with semen viral loads generally detected in individuals with blood viral loads > 10,000 cp/ml. However, we found 1 individual with undetectable viral loads (<20cp/ml) and 2 individuals with very low blood viral load (97 and 333cp/ml), but with detectable HIV-1 in semen (485–1157 copies/semen sample). Blood viral loads in the first individual were undetectable when tested three times over the prior 5 years. Conclusions Semen HIV-1 viral loads are usually related to blood viral loads, as we confirm. Nonetheless, this was not true in a substantial minority of individuals suggesting unexpectedly high levels of replication in the male genital tract in a few individuals, despite otherwise effective immune control. This may reflect establishment of a local reservoir of HIV-1 populations

The prevalence of human papillomavirus infections and associated risk factors in men-who-have-sex-with-men in Cape Town, South Africa

Abstract Background We investigated the prevalence of human papillomavirus (HPV) infection and associated behavioural risk factors in men-who-have-sex-with-men (MSM) attending a clinical service in Cape Town, South Africa. Methods MSM were enrolled at the Ivan Toms Centre for Men’s Health in Cape Town. A psychosocial and sexual behavioral risk questionnaire was completed for each participant and urine, oro-pharyngeal and anal swabs were collected for HPV testing using the Linear Array HPV Genotyping Test. Logistic regression analyses were performed to determine sexual risk factors associated with HPV infection at the three anatomical sites. Results The median age of all 200 participants was 32 years (IQR 26-39.5), of which 31.0 % were black, 31.5 % mixed race/coloured and 35.5 % white. The majority of the participants (73.0 %) had completed high school, 42.0 % had a tertiary level qualification and 69.0 % were employed. HPV genotypes were detected in 72.8 % [95 % CI: 65.9–79.0 %], 11.5 % [95 % CI: 7.4–16.8 %] and 15.3 % [95 % CI: 10.5–21.2 %] of anal, oro-pharyngeal and urine specimens, respectively. Prevalence of high-risk (HR)-HPV types was 57.6 % [95 % CI: 50.3–64.7 %] in anal samples, 7.5 % [95 % CI: 4.3–12.1 %] in oro-pharyngeal samples and 7.9 % [95 % CI: 4.5–12.7 %] in urine, with HPV-16 being the most common HR-HPV type detected at all sites. HPV-6/11/16/18 was detected in 40.3 % [95 % CI: 33.3–47.6 %], 4.5 % [95 % CI: 2.1–8.4 %] and 3.2 % [95 % CI: 1.2–6.8 %] of anal, oro-pharyngeal and urine samples, respectively. Multiple HPV types were more common in the anal canal of MSM while single HPV types constituted the majority of HPV infections in the oropharynx and urine. Among the 88 MSM (44.0 %) that were HIV positive, 91.8 % [95 % CI: 83.8–96.6 %] had an anal HPV infection, 81.2 % [95 % CI: 71.2–88.8 %] had anal HR-HPV and 85.9 % [95 % CI: 76.6–92.5 %] had multiple anal HPV types. Having sex with men only, engaging in group sex in lifetime, living with HIV and practising receptive anal intercourse were the only factors independently associated with having any anal HPV infection. Conclusions Anal HPV infections were common among MSM in Cape Town with the highest HPV burden among HIV co-infected MSM, men who have sex with men only and those that practiced receptive anal intercourse. Behavioural intervention strategies and the possible roll-out of HPV vaccines among all boys are urgently needed to address the high prevalence of HPV and HIV co-infections among MSM in South Africa

Clinical and Financial Burdens of Secondary Level Care in a Public Sector Antiretroviral Roll-Out Setting: GF Jooste Hospital

Background: Antiretroviral therapy is being rolled out across South Africa. While efforts have been made to assess the costs of providing antiretroviral therapy (ART) via accredited service points, little information is available on its downstream costs, particularly in public secondary level hospitals. Objectives: (1) To determine the cost of care for inpatients and outpatients at a dedicated Antiretroviral Referral Unit treating and caring for antiretroviral-related conditions in a South African peri-urban setting, (2) to identify key epidemiological cost drivers, and (3) to examine the associated clinical and outcome data. Methods: A prospective costing study on 48 outpatients and 25 inpatients was conducted from a health system perspective. Incremental economic costs and clinical data were collected from primary sources at GF Jooste Hospital, Cape Town, over a one month period (March 2005). Results: Incremental cost per outpatient was R1280 and per inpatient R5802. Costs were dominated by medical staff costs (62% inpatient and 58% outpatient respectively). Inpatient and outpatient diagnoses and costs were dominated by infections (55% and 67%; 49% and 54% respectively). Most inpatients and outpatients were judged by attending physicians to have improved or stabilized as a result of treatment (52% and 59% respectively). Conclusions: The costs of providing secondary level care for patients on or immediately preceding ART initiation can be significant and should be included in the government’s strategic planning so that (1) the service can be expanded to meet current and future needs and (2) to avoid crowding out other secondary level health services